Municipal budgetary educational institution

"School No. 129"

Avtozavodskoy district of Nizhny Novgorod

Scientific society students

Analysis of drugs.

Performed: Tyapkina Victoria

10th grade student

Scientific supervisors:

Novik I.R. Associate Professor, Department of Chemistry and Chemical Education, NSPU named after K. Minina; Ph.D.;

Sidorova A.V . chemistry teacher

MBOU "School No. 129".

Nizhny Novgorod

2016

Content

Introduction………………………………………………………………………….3

Chapter 1. Information about medicinal substances

1. History of the use of medicinal substances………………………….5

   Classification of drugs…………………………….8

   The composition and physical properties of medicinal substances……………….11

   Physiological and pharmacological properties of medicinal substances……………………………………………………………………….16

   Conclusions to Chapter 1…………………………………………………………….19

Chapter 2

2.1. The quality of medicines……………………………………21

2.2. Analysis of drugs……………………………………...25

Conclusion…………………………………………………………………….31

Bibliographic list…………………………………………………..32

Introduction

“Your medicine is in yourself, but you don’t feel it, and your illness is because of yourself, but you don’t see it. You think that you are a small body, but a huge world is hidden (collapsed) in you.

Ali ibn Abu Talib

Medicinal substance - an individual chemical compound or biological substance that has therapeutic or prophylactic properties.

Mankind has been using medicines since ancient times. So in China for 3000 years BC. substances of plant, animal origin, minerals were used as medicines. In India, the medical book "Ayurveda" (6-5 centuries BC) was written, which provides information about medicinal plants. The ancient Greek physician Hippocrates (460-377 BC) used over 230 medicinal plants in his medical practice.

In the Middle Ages, many medicines were discovered and introduced into medical practice thanks to alchemy. In the 19th century, due to the general progress of the natural sciences, the arsenal of medicinal substances expanded significantly. Medicinal substances obtained by chemical synthesis appeared (chloroform, phenol, salicylic acid, acetylsalicylic acid, etc.).

In the 19th century, the chemical and pharmaceutical industry began to develop, ensuring the mass production of medicines. Medicinal products are substances or mixtures of substances used for the prevention, diagnosis, treatment of diseases, as well as for the regulation of other conditions. Modern drugs are developed in pharmaceutical laboratories based on plant, mineral and animal raw materials, as well as chemical synthesis products. Medicines undergo laboratory clinical trials and only after that they are used in medical practice.

Currently, a huge number of medicinal substances are being created, but there are also many fakes. According to the World Health Organization (WHO), the highest percentage counterfeits account for antibiotics - 42%. In our country, according to the Ministry of Health, counterfeit antibiotics today account for 47% of the total number of drugs - fakes, hormonal drugs - 1%, antifungals, analgesics and drugs that affect the function of the gastrointestinal tract - 7%.

The topic of the quality of medicines will always be relevant, since our health depends on the consumption of these substances, therefore, we took these substances for further research.

Purpose of the study: get acquainted with the properties of drugs and establish their quality using chemical analysis.

Object of study: analgin, aspirin (acetylsalicylic acid), paracetamol.

Subject of study: quality composition of drugs.

Tasks:

To study the literature (scientific and medical) in order to establish the composition of the studied medicinal substances, their classification, chemical, physical and pharmaceutical properties.

Select a method suitable for establishing the quality of selected drugs in the analytical laboratory.

Conduct a study of the quality of medicines according to the chosen method of qualitative analysis.

Analyze the results, process them and formalize the work.

Hypothesis: after analyzing the quality of medicines according to the selected methods, it is possible to determine the quality of the authenticity of medicines and draw the necessary conclusions.

Chapter 1. Information about medicinal substances

1. History of the use of medicinal substances

The study of medicines is one of the most ancient medical disciplines. Apparently, drug therapy in its most primitive form already existed in primitive human society. Eating certain plants, watching animals eating plants, a person gradually got acquainted with the properties of plants, including their therapeutic effect. The fact that the first medicines were mainly of plant origin, we can judge from the most ancient writing samples that have come down to us. One of the Egyptian papyri (17th century BC) describes a number of herbal remedies; some of them are still used today (for example, castor oil, etc.).

It is known that in ancient Greece, Hippocrates (3rd century BC) used various medicinal plants to treat diseases. At the same time, he recommended using whole, unprocessed plants, believing that only in this case they retain their healing power. Later, doctors came to the conclusion that medicinal plants contain active principles that can be separated from unnecessary, ballast substances. In the 2nd century A.D. e. The Roman physician Claudius Galen widely used various extracts (extracts) from medicinal plants. To extract active principles from plants, he used wines and vinegars. Alcohol extracts from medicinal plants are still used today. These are tinctures and extracts. In memory of Galena, tinctures and extracts are classified as so-called galenic preparations.

A large number of herbal medicines are mentioned in the writings of the largest Tajik physician of the Middle Ages, Abu Ali Ibn-Sina (Avicenna), who lived in the 11th century. Some of these remedies are still used today: camphor, preparations of henbane, rhubarb, Alexandrian leaf, ergot, etc. In addition to herbal medicines, physicians used some inorganic medicinal substances. For the first time, substances of inorganic nature began to be widely used in medical practice by Paracelsus (XV-XVI centuries). He was born and educated in Switzerland, was a professor in Basel and then moved to Salzburg. Paracelsus introduced many drugs of inorganic origin into medicine: compounds of iron, mercury, lead, copper, arsenic, sulfur, antimony. Preparations of these elements were prescribed to patients in large doses, and often, simultaneously with a therapeutic effect, they exhibited a toxic effect: they caused vomiting, diarrhea, salivation, etc. This, however, was quite consistent with the ideas of that time about drug therapy. It should be noted that medicine has long held the idea of ​​a disease as something that entered the patient's body from the outside. To "expel" the disease, substances were prescribed that cause vomiting, diarrhea, salivation, profuse sweating, and massive bloodletting was used. One of the first physicians to refuse treatment with massive doses of drugs was Hahnemann (1755-1843). He was born and trained in medicine in Germany and then worked as a doctor in Vienna. Hahnemann drew attention to the fact that patients who received drugs in large doses recover less often than patients who did not receive such treatment, so he suggested a sharp reduction in the dosage of drugs. Without any evidence for this, Hahnemann argued that the therapeutic effect of drugs increases with decreasing dose. Following this principle, he prescribed drugs to patients in very small doses. As experimental verification shows, in these cases, the substances do not have any pharmacological effect. According to another principle, proclaimed by Hahnemann and also completely unfounded, any medicinal substance causes a "drug disease". If the "drug disease" is similar to the "natural disease", it will supplant the latter. Hahnemann's teaching was called "homeopathy" (homoios - the same; pathos - suffering, that is, the treatment of like with like), and Hahnemann's followers began to be called homeopaths. Homeopathy has changed little since Hahnemann's time. The principles of homeopathic treatment are not substantiated experimentally. Tests of the homeopathic method of treatment in the clinic, carried out with the participation of homeopaths, did not show its significant therapeutic effect.

The emergence of scientific pharmacology dates back to the 19th century, when individual active principles were isolated from plants in their pure form for the first time, the first synthetic compounds were obtained, and when, thanks to the development of experimental methods, it became possible to experimentally study the pharmacological properties of medicinal substances. In 1806, morphine was isolated from opium. In 1818, strychnine was isolated, in 1820 - caffeine, in 1832 - atropine, in subsequent years - papaverine, pilocarpine, cocaine, etc. late XIX century, about 30 similar substances (plant alkaloids) were isolated. The isolation of the pure active principles of plants in an isolated form made it possible to accurately determine their properties. This was facilitated by the emergence of experimental research methods.

The first pharmacological experiments were carried out by physiologists. In 1819, the famous French physiologist F. Magendie first studied the effect of strychnine on a frog. In 1856, another French physiologist, Claude Bernard, analyzed the action of curare on a frog. Almost simultaneously and independently of Claude Bernard, similar experiments were carried out in St. Petersburg by the famous Russian forensic physician and pharmacologist E.V. Pelikan.

1.2. Classification of medicinal preparations

The rapid development of the pharmaceutical industry has led to the creation of a huge number of drugs (currently hundreds of thousands). Even in specialized literature, such expressions as "avalanche" of drugs or "drug jungle" appear. Naturally, the current situation makes it very difficult to study medicines and their rational use. There is an urgent need to develop a classification of drugs that would help doctors navigate the mass of drugs and choose the best drug for the patient.

Medicinal product - a pharmacological agent authorized by the authorized body of the relevant countryin the prescribed manner for use in the treatment, prevention or diagnosis of disease in humans or animals.

Medicines can be classified according to the following principles:

– therapeutic use (anticancer, antianginal, antimicrobial agents);

– pharmacological agents (vasodilators, anticoagulants, diuretics);

– chemical compounds (alkaloids, steroids, glycoids, benzodiazenines).

Classification of medicines:

I. Means acting on the central nervous system (central nervous system).

1 . Means for anesthesia;

2. Sleeping pills;

3. Psychotropic drugs;

4. Anticonvulsants (antiepileptic drugs);

5. Means for the treatment of parkinsonism;

6. Analgesics and non-steroidal anti-inflammatory drugs;

7. Emetic and antiemetic drugs.

II.Drugs acting on the peripheral NS (nervous system).

1. Means acting on peripheral cholinergic processes;

2. Means acting on peripheral adrenergic processes;

3. Dophalin and dopamineric drugs;

4. Histamine and antihistamines;

5. Serotinin, serotonin-like and antiserotonin drugs.

III. Means that act mainly in the area of ​​\u200b\u200bsensitive nerve endings.

1. Local anesthetic drugs;

2. Enveloping and adsorbing agents;

3. Astringents;

4. Means, the action of which is mainly associated with irritation of the nerve endings of the mucous membranes and skin;

5. Expectorants;

6. Laxatives.

IV. Means acting on the CCC (cardiovascular system).

1. Cardiac glycosides;

2. Antiarrhythmic drugs;

3. Vasodilators and antispasmodics;

4. Antianginal drugs;

5. Drugs that improve cerebral circulation;

6. Antihypertensive drugs;

7. Antispasmodics of different groups;

8. Substances affecting the angiotensin system.

V. Drugs that enhance the excretory function of the kidneys.

1. Diuretics;

2. Means that promote the excretion of uric acid and the removal of urinary calculi.

VI. Choleretic agents.

VII. Drugs that affect the muscles of the uterus (uterine drugs).

1. Means that stimulate the muscles of the uterus;

2. Means that relax the muscles of the uterus (tocolytics).

VIII. Means that affect metabolic processes.

1. Hormones, their analogues and antihormonal drugs;

2. Vitamins and their analogues;

3. Enzyme preparations and substances with antienzymatic activity;

4. Means that affect blood coagulation;

5. Preparations of hypocholesterolemic and hypolipoproteinemic action;

6. Amino acids;

7. Plasma-substituting solutions and means for parenteral nutrition;

8. Drugs used to correct the acid-base and ionic balance in the body;

9. Various drugs that stimulate metabolic processes.

IX. Drugs that modulate immune processes ("immunomodulators").

1. Drugs that stimulate immunological processes;

2. Immunosuppressive drugs (immunosuppressors).

X. Preparations of various pharmacological groups.

1. Anorexigenic substances (substances that suppress appetite);

2. Specific antidotes, complexones;

3. Preparations for the prevention and treatment of radiation sickness syndrome;

4. Photosensitizing drugs;

5. Special means for the treatment of alcoholism.

1. Chemotherapeutic agents;

2. Antiseptics.

XII. Drugs used to treat malignant neoplasms.

1. Chemotherapeutic agents.

2. Enzyme preparations used for the treatment of oncological diseases;

3. Hormonal drugs and inhibitors of hormone formation, used primarily for the treatment of tumors.

1. Composition and physical properties of medicinal substances

In this work, we decided to investigate the properties of medicinal substances that are part of the most commonly used drugs and are mandatory in any home first aid kit.

Analgin

Translated, the word "analgin" means the absence of pain. It is difficult to find a person who did not take analgin. Analgin is the main drug in the group of non-narcotic analgesics - drugs that can reduce pain without affecting the psyche. Reducing pain is not the only pharmacological effect of analgin. The ability to reduce the severity of inflammatory processes and the ability to reduce elevated body temperature are no less valuable (antipyretic and anti-inflammatory effect). However, analgin is rarely used for anti-inflammatory purposes, there are much more for this. effective means. But with fever and pain, he is just right.

Metamizole (analgin) for many decades has been an emergency drug in our country, and not a remedy for the treatment of chronic diseases. That is how he should remain.

Analgin was synthesized in 1920 in search of an easily soluble form of amidopyrine. This is the third main direction in the development of painkillers. Analgin, according to statistics, is one of the most beloved drugs, and most importantly, it is available to everyone. Although in fact he is very few years old - only about 80. Experts developed Analgin specifically to deal with severe pain. Indeed, he saved a lot of people from torment. It was used as an affordable pain reliever, since there was no wide range of painkillers at that time. Of course, narcotic analgesics were used, but the medicine of that time already had sufficient data on, and this group of drugs was used only in appropriate cases. The drug Analgin is very popular in medical practice. Already one name says about what Analgin helps from and in what cases it is used. After all, in translation it means "absence of pain." Analgin belongs to the group of non-narcotic analgesics, i.e. drugs that can reduce pain without affecting the psyche.

In clinical practice, analgin (metamisole sodium) was first introduced in Germany in 1922. Analgin became indispensable for hospitals in Germany during the Second World War. For many years it remained a very popular drug, but this popularity also reverse side: its widespread and practically uncontrolled use as an over-the-counter drug led in the 70s. of the last century to deaths from agranulocytosis (an immune blood disease) and shock. This has resulted in analgin being banned in a number of countries while remaining available over the counter in others. The risk of serious side effects when using combined preparations containing metamizole is higher than when taking "pure" analgin. Therefore, in most countries, such funds have been withdrawn from circulation.

Trade name: a nalgin.
International name: Metamizole sodium (Metamizole sodium).
Group affiliation: Analgesic non-narcotic agent.
Dosage form: capsules, solution for intravenous and intramuscular administration, rectal suppositories [for children], tablets, tablets [for children].

Chemical composition and physiochemical properties analgin

Analgin. analginum.

Metamizole sodium.Metamizolum natricum

Chemical Name: 1-phenyl-2,3-dimethyl-4-methyl-aminopyrazolone-5-N-methane - sodium sulfate

Gross formula: C 13 H 18 N 3 NaO 5 S

Fig.1

Appearance: colorless needle-shaped crystals of a bitter taste, odorless.

Paracetamol

In 1877 Harmon Northrop Morse synthesized paracetamol at Johns Hopkins University in the reduction of p-nitrophenol with tin in glacial acetic acid, but it was not until 1887 that clinical pharmacologist Joseph von Mering tested paracetamol on patients. In 1893, von Mehring published an article reporting the clinical results of paracetamol and phenacetin, another aniline derivative. Von Mering argued that, unlike phenacetin, paracetamol has some ability to cause methemoglobinemia. Paracetamol was then quickly abandoned in favor of phenacetin. Bayer began selling phenacetin as a leading pharmaceutical company at the time. Introduced into medicine by Heinrich Dreser in 1899, phenacetin has been popular for many decades, especially in the widely advertised over-the-counter "headache potion" usually containing phenacetin, an aminopyrine derivative of aspirin, caffeine, and sometimes barbiturates.

Tradename:Paracetamol

International name:paracetamol

Group affiliation: analgesic non-narcotic agent.

Dosage form:tablets

Chemical composition and physico-chemical properties of paracetamol

Paracetamol. paracetamolum.

Gross - formula:C 8 H 9 NO 2 ,

Chemical Name: N-(4-Hydroxyphenyl)acetamide.

Appearance: white or white with cream or pink tint Fig.2 crystalline powder. Easilyoensh679c969soluble in alcohol, insoluble in water.

Aspirin (acetysalicylic acid)

Aspirin was first synthesized in 1869. This is one of the most famous and widely used drugs. It turned out that the history of aspirin is typical of many other drugs. As early as 400 BC, the Greek physician Hippocrates recommended that patients chew willow bark to relieve pain. Of course, he could not know about the chemical composition of the painkillers, but they were derivatives of acetylsalicylic acid (chemists found out only two millennia later). In 1890, F. Hoffman, who worked for the German company Bayer, developed a method for the synthesis of acetylsalicylic acid, the basis of aspirin. Aspirin was introduced to the market in 1899, and from 1915 began to be sold without prescriptions. The mechanism of analgesic action was discovered only in the 1970s. In recent years, aspirin has become a tool for the prevention of cardiovascular disease.

Tradename : Aspirin.

international title : acetylsalicylic acid.

Group affiliation : non-steroidal anti-inflammatory drug.

Dosage form: tablets.

Chemical composition and physico-chemical properties of aspirin

Acetylsalicylic acid.Acidum acetylsalicylicum

Gross - formula: FROM 9 H 8 ABOUT 4

Chemical Name: 2-acetoxy-benzoic acid.

Appearance :hpure substance is a white crystalline powder, almost withoutdictionaryodor, sour taste.

Dibazol

Dibazol was created in the Soviet Union in the middle of the last century. For the first time this substance was noted in 1946 as the most physiologically active benzimidazole salt. In the course of experiments conducted on laboratory animals, the ability of a new substance to improve the transmission of nerve impulses in the spinal cord was noticed. This ability was confirmed during clinical trials, and in the early 1950s the drug was introduced into clinical practice for the treatment of diseases of the spinal cord, in particular, poliomyelitis. Currently in use as a means to strengthen the immune system, improve metabolism and increase stamina.

Tradename: Dibazol.

international title : Dibazol. 2nd: Benzylbenzimidazole hydrochloride.

Group affiliation : a drug of the group of peripheral vasodilators.

Dosage form : solution for intravenous and intramuscular administration, rectal suppositories [for children], tablets.

Chemical composition and physico-chemical properties: Dibazol

It is highly soluble in water, but poorly soluble in alcohol.

Gross formula :C 14 H 12 N 2 .

chemical name : 2-(Phenylmethyl)-1H-benzimidazole.

Appearance : benzimidazole derivative,

Figure 4 is white, white-yellow or

light gray crystalline powder.

1. Physiological and pharmacological action of drugs

Analgin.

Pharmacological properties:

Analgin belongs to the group of non-steroidal anti-inflammatory drugs, the effectiveness of which is due to the activity of metamizole sodium, which:

Blocks the passage of pain impulses through the bundles of Gaulle and Burdakh;

Significantly increases heat transfer, which makes it expedient to use when high temperature Analgin;

Promotes an increase in the threshold of excitability of the thalamic centers of pain sensitivity;

It has a mild anti-inflammatory effect;

Promotes some antispasmodic effect.

The activity of Analgin develops approximately 20 minutes after ingestion, reaching a maximum after 2 hours.

Indications for use

According to instructions,Analgin is used to eliminate pain syndrome caused by diseases such as:

Arthralgia;

Intestinal, biliary and renal colic;

Burns and injuries;

Shingles;

Neuralgia;

decompression sickness;

myalgia;

Algodysmenorrhea, etc.

Effective is the use of Analgin to eliminate toothache and headache, as well as postoperative pain syndrome. In addition, the drug is used for febrile syndrome caused by insect bites, infectious and inflammatory diseases or post-transfusion complications.

To eliminate the inflammatory process and reduce the temperature, Analgin is rarely used, since there are more effective means for this.

Paracetamol

Pharmacological properties:

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. It binds to plasma proteins by 15%. Paracetamol crosses the blood-brain barrier. Less than 1% of the dose of paracetamol taken by a nursing mother passes into breast milk. Paracetamol is metabolized in the liver and excreted in the urine, mainly in the form of glucuronides and sulfonated conjugates, less than 5% is excreted unchanged in the urine.

Indications for use

for rapid relief of headache, including migraine pain;

toothache;

neuralgia;

muscular and rheumatic pain;

as well as with algomenorrhea, pain in injuries, burns;

to reduce fever with colds and flu.

Aspirin

Pharmacological properties:

Acetylsalicylic acid (ASA) has analgesic, antipyretic and anti-inflammatory effects due to the inhibition of cyclooxygenase enzymes involved in the synthesis of prostaglandins.

ASA in the dose range of 0.3 to 1.0 g is used to reduce fever in diseases such as colds andand to relieve joint and muscle pain.
ASA inhibits platelet aggregation by blocking the synthesis of thromboxane A 2 in platelets.

Indications for use

for symptomatic relief of headache;

toothache;

sore throat;

pain in muscles and joints;

back pain;

elevated body temperature with colds and other infectious and inflammatory diseases (in adults and children over 15 years old)

Dibazol

Pharmacological properties

Vasodilating agent; has a hypotensive, vasodilating effect, stimulates the function of the spinal cord, has a moderate immunostimulating activity. Has a direct antispasmodic effect on smooth muscles blood vessels and internal organs. Facilitates synaptic transmission in the spinal cord. It causes an expansion (short) of the cerebral vessels and is therefore especially indicated in forms of arterial hypertension caused by chronic hypoxia of the brain due to local circulatory disorders (sclerosis of the cerebral arteries). In the liver, dibazol undergoes metabolic transformations by methylation and carboxyethylation with the formation of two metabolites. It is mainly excreted by the kidneys, and to a lesser extent - through the intestines.

Indications for use

Various conditions accompanied by arterial hypertension, incl. and hypertension, hypertensive crises;

Spasm of smooth muscles of internal organs (intestinal, hepatic, renal colic);

Residual effects of poliomyelitis, facial paralysis, polyneuritis;

Prevention of viral infectious diseases;

Increasing the body's resistance to external adverse effects.

1. Conclusions to chapter 1

1) It is revealed that the doctrine of medicines is one of the most ancient medical disciplines. Drug therapy in its most primitive form already existed in primitive human society. The first medicines were mostly of plant origin. The emergence of scientific pharmacology dates back to the 19th century, when individual active principles were isolated from plants in their pure form for the first time, the first synthetic compounds were obtained, and when, thanks to the development of experimental methods, it became possible to experimentally study the pharmacological properties of medicinal substances.

2) It has been established that drugs can be classified according to the following principles:

– therapeutic use;

–pharmacological agents;

– chemical compounds.

3) The chemical composition and physical properties of analgin, paracetamol and aspirin preparations, which are indispensable in a home first aid kit, are considered. It has been established that the medicinal substances of these preparations are complex derivatives of aromatic hydrocarbons and amines.

4) The pharmacological properties of the studied drugs are shown, as well as indications for their use and physiological effects on the body. Most often, these medicinal substances are used as antipyretic and analgesic.

Chapter 2. Practical part. Study of the quality of medicines

2.1. The quality of medicines

In the definition of the World Health Organization, a falsified (counterfeit) medicinal product (FLS) means a product that is deliberately and unlawfully provided with a label that incorrectly indicates the authenticity of the drug and (or) the manufacturer.

The concepts of "counterfeit", "counterfeit" and "fake" legally have certain differences, but for an ordinary citizen they are identical. A fake is a drug produced with a change in its composition, while maintaining its appearance, and often accompanied by false information about its composition . A drug is considered counterfeit, the production and further sale of which is carried out under someone else's individual characteristics (trademark, name or place of origin) without the permission of the patent holder, which is a violation of intellectual property rights.

A counterfeit drug is often regarded as counterfeit and counterfeit. In the Russian Federation, a counterfeit drug is considered to be a drug that is recognized as such by Roszdravnadzor after a thorough check with the publication of relevant information on the website of Roszdravnadzor. From the date of publication, the circulation of FLS should be terminated with withdrawal from the distribution network and placement in a quarantine zone separately from other drugs. Moving this FLS is a violation.

Counterfeit drugs are considered the fourth public health scourge after malaria, AIDS and smoking. For the most part, fakes do not match the quality, effectiveness or side effects of the original drugs, causing irreparable harm to the health of a sick person; are produced and distributed without the control of the relevant authorities, causing enormous financial harm to legitimate drug manufacturers and the state. Death from FLS is among the top ten causes of death.

Experts identify four main types of counterfeit drugs.

1st type - "dummy medicines". In these "medicines", as a rule, there are no main therapeutic components. Those who take them do not feel the difference, and even for a number of patients, the use of "pacifiers" can have a positive effect due to the placebo effect.

2nd type - “drugs-imitators”. Such “drugs” use active ingredients that are cheaper and less effective than those in a genuine drug. The danger lies in the insufficient concentration of active substances that patients need.

3rd type - Altered drugs. These "drugs" contain the same active substance as the original product, but in larger or smaller quantities. Naturally, the use of such drugs is unsafe, because it can lead to increased side effects (especially with an overdose).

4th type - copy medicines. They are among the most common types of counterfeit drugs in Russia (up to 90% of the total number of counterfeits), usually produced by clandestine industries and, through one or another channel, getting into batches of legal drugs. These drugs contain the same active ingredients as legal drugs, but there are no guarantees of the quality of the substances underlying them, compliance with the norms of technological processes of production, etc. Therefore, the risk of the consequences of taking such drugs is increased.

Offenders are brought to administrative responsibility under Art. 14.1 of the Code of Administrative Offenses of the Russian Federation, or criminal liability for which, due to the absence of liability for falsification in the Criminal Code, comes under several offenses and is mainly qualified as fraud (Article 159 of the Criminal Code of the Russian Federation) and illegal use of a trademark (Article 180 Criminal Code of the Russian Federation).

The Federal Law "On Medicines" provides a legal basis for the seizure and destruction of FLS, both those produced in Russia and imported from abroad, and those in circulation on the domestic pharmaceutical market.

Part 9 of Article 20 establishes a ban on the import into the territory of Russia of medicines that are fakes, illegal copies or counterfeit medicines. The customs authorities are obliged to confiscate and destroy them if found.

Art. 31, establishes a ban on the sale of medicinal products that have become unusable, have expired or are recognized as counterfeit. They are also subject to destruction. The Ministry of Health of Russia, by order No. 382 of December 15, 2002, approved the Instruction on the procedure for the destruction of medicines that have become unusable, medicines with an expired shelf life and medicines that are fakes or illegal copies. But the instructions have not yet been amended in accordance with the additions to the Federal Law "On Medicines" of 2004 on counterfeit and substandard medicines, which now define and indicate the prohibition of their circulation and withdrawal from circulation, and also proposed government bodies bring regulatory legal acts in line with this law.

Roszdravnadzor issued a letter No. 01I-92/06 dated 08.02.2006 “On the organization of the work of the territorial departments of Roszdravnadzor with information on substandard and falsified medicines”, which contradicts the legal norms of the Law on Medicines and negates the fight against counterfeiting. The law prescribes to withdraw from circulation and destroy counterfeit medicines, and Roszdravnadzor (paragraph 4, clause 10) suggests that territorial departments control the withdrawal from circulation and destruction of counterfeit medicines. By proposing 16 to exercise control only over the return to the owner or owner for further destruction, Roszdravnadzor allows the continued circulation of counterfeit medicines and return them to the owner, that is, the counterfeiting criminal himself, which grossly violates the Law and the Instructions for destruction. At the same time, there are often references to the Federal Law of December 27, 2002 No. 184-FZ “On Technical Regulation”, in Art. 36-38 of which establishes the procedure for the return to the manufacturer or seller of products that do not meet the requirements of the technical regulation. However, it must be borne in mind that this procedure does not apply to counterfeit medicines that are produced without observing the technical regulations, by whom and where.

From January 1, 2008, in accordance with Art. 2 of the Federal Law of December 18, 2006 No. 231-FZ “On the Enactment of Part Four of the Civil Code of the Russian Federation”, new legislation on the protection of intellectual property came into force, the objects of which include means of individualization, including trademarks, with through which drug manufacturers protect the rights to their products. The fourth part of the Civil Code of the Russian Federation (part 4 of article 1252) defines counterfeit material carriers of the results of intellectual activity and means of individualization

The pharmaceutical industry in Russia today needs a total scientific and technical re-equipment, as its fixed assets are worn out. It is necessary to introduce new standards, including GOST R 52249-2004, without which the production of high-quality medicines is not possible.

2.2. The quality of medicines.

For the analysis of drugs, we used methods for determining the presence of amino groups in them (lignin test), phenolic hydroxyl, heterocycles, carboxyl group, and others. (We took the methods from methodological developments for students in medical colleges and on the Internet).

Reactions with the drug analgin.

Determination of the solubility of analgin.

1 .Dissolved 0.5 tablets of analgin (0.25 g) in 5 ml of water, and the second half of the tablet in 5 ml of ethyl alcohol.

Fig.5 Weighing the preparation Fig.6 Grinding the preparation

Output: analgin is well dissolved in water, but practically does not dissolve in alcohol.

Determining the presence of a CH group 2 SO 3 Na .

Heated 0.25 g of the drug (half a tablet) in 8 ml of dilute hydrochloric acid.

Fig.7 Heating the preparation

Found: first the smell of sulfur dioxide, then formaldehyde.

Output: this reaction makes it possible to prove that analgin contains a formaldehyde sulfonate group.

Determining the properties of a chameleon

1 ml of the resulting analgin solution was added 3-4 drops of a 10% solution of iron chloride (III). When analgin interacts with Fe 3+ oxidation products are formed

painted in blue color, which then turns into dark green, and then orange, i.e. exhibits the properties of a chameleon. This means that the drug is of high quality.

For comparison, we took preparations with different expiration dates and identified, using the above method, the quality of the preparations.

Fig. 8 The appearance of the property of a chameleon

Fig.9 Comparison of drug samples

Output: the reaction with the drug of a later production date proceeds according to the chameleon principle, which indicates its quality. But the drug of earlier production did not show this property, it follows that this drug cannot be used for its intended purpose.

4. The reaction of analgin with hydroperite. ("Smoke bomb")

the reaction proceeds immediately in two places: at the sulfo group and the methylaminyl group. Accordingly, hydrogen sulfide, as well as water and oxygen, can be formed at the sulfo group.

-SO3 + 2H2O2 = H2S + H2O + 3O2.

The resulting water leads to partial hydrolysis at the C - N bond and methylamine is split off, and water and oxygen are also formed:

-N(CH3) + H2O2 = H2NCH3 + H2O + 1/2 O2

And finally it becomes clear what kind of smoke is obtained in this reaction:

Hydrogen sulfide reacts with methylamine to form methylammonium hydrosulfide:

H2NCH3 + H2S = HS.

And the suspension of its small crystals in the air creates a visual sensation of "smoke".

Rice. 10 Reaction of analgin with hydroperite

Reactions with the drug paracetamol.

Determination of acetic acid

Fig.11 Heating a solution of paracetamol with hydrochloric acid Fig.12 Mixture cooling

Output: the smell of acetic acid that appears means that this drug is really paracetamol.

Determination of the phenol derivative of paracetamol.

A few drops of 10% ferric chloride solution were added to 1 ml of paracetamol solution (III).

Fig. 13 The appearance of blue coloration

Observed: blue color indicates the presence of a phenol derivative in the composition of the substance.

0.05 g of the substance was boiled with 2 ml of dilute hydrochloric acid for 1 minute and 1 drop of potassium dichromate solution was added.

Fig.14 Boiling with hydrochloric acid Fig.15 Oxidation with potassium dichromate

Observed: the appearance of a blue-violet color,does not turn red.

Output: in the course of the reactions, the qualitative composition of the paracetamol preparation was proved, and it was found that it is a derivative of aniline.

Reactions with aspirin.

For the experiment, we used aspirin tablets manufactured by the Pharmstandard-Tomskhimfarm pharmaceutical production factory. Valid until May 2016.

Determination of the solubility of aspirin in ethanol.

0.1 g of drugs were added to test tubes and 10 ml of ethanol were added. At the same time, partial solubility of aspirin was observed. Test tubes with substances were heated on an alcohol lamp. The solubility of drugs in water and ethanol was compared.

Output: The results of the experiment showed that aspirin is more soluble in ethanol than in water, but precipitates in the form of needle crystals. That's whyThe use of aspirin in conjunction with ethanol is unacceptable. It should be concluded that the use of alcohol-containing drugs in conjunction with aspirin, and even more so with alcohol, is inadmissible.

Determination of a phenol derivative in aspirin.

0.5 g of acetylsalicylic acid, 5 ml of sodium hydroxide solution were mixed in a beaker and the mixture was boiled for 3 minutes. The reaction mixture was cooled and acidified with dilute sulfuric acid until a white crystalline precipitate formed. The precipitate was filtered off, part of it was transferred into a test tube, 1 ml of distilled water was added to it, and 2-3 drops of ferric chloride solution were added.

Hydrolysis of the ester bond leads to the formation of a phenol derivative, which with ferric chloride (3) gives a violet color.

Fig.16 Boiling a mixture of aspirin Fig.17 Oxidation with a solution Fig.18 Qualitative reaction

with sodium hydroxide of sulfuric acid for a phenol derivative

Output: hydrolysis of aspirin produces a phenol derivative, which gives a violet color.

A phenol derivative is a substance that is very dangerous for human health, which affects the appearance of side effects on the human body when taking acetylsalicylic acid. Therefore, it is necessary to strictly follow the instructions for use (this fact was mentioned back in the 19th century).

2.3. Conclusions to chapter 2

1) It is established that a huge number of medicinal substances are currently being created, but also a lot of fakes. The topic of the quality of medicines will always be relevant, since our health depends on the consumption of these substances. The quality of medicines is determined by GOST R 52249 - 09. In the definition of the World Health Organization, a counterfeit (counterfeit) drug (FLS) means a product that is intentionally and unlawfully provided with a label that incorrectly indicates the authenticity of the drug and (or) manufacturer.

2) For the analysis of drugs, we used methods for determining the presence of amino groups in them (lignin test) phenolic hydroxyl, heterocycles, carboxyl group and others. (We took the methods from the teaching aid for students of chemical and biological specialties).

3) During the experiment, the qualitative composition of analgin, dibazol, paracetamol, aspirin preparations and the quantitative composition of analgin were proved. The results and more detailed conclusions are given in the text of the work in Chapter 2.

Conclusion

The purpose of this study was to get acquainted with the properties of some medicinal substances and to establish their quality using chemical analysis.

I have analyzed literary sources in order to establish the composition of the studied medicinal substances that are part of analgin, paracetamol, aspirin, their classification, chemical, physical and pharmaceutical properties. We have selected a method suitable for establishing the quality of selected drugs in an analytical laboratory. Studies of the quality of drugs were carried out according to the chosen method of qualitative analysis.

Based on the work done, it was found that all medicinal substances correspond to the quality of GOST.

Of course, it is impossible to consider the whole variety of drugs, their effect on the body, the features of the use and dosage forms of these drugs, which are common. chemicals. A more detailed acquaintance with the world of drugs awaits those who will continue to be engaged in pharmacology and medicine.

I would also like to add that despite the rapid development of the pharmacological industry, scientists have not yet been able to create a single drug without side effects. Each of us should remember this: because, when we feel unwell, we first of all go to the doctor, then to the pharmacy, and the treatment process begins, which is often expressed in unsystematic medication.

Therefore, in conclusion, I would like to give recommendations on the use of drugs:

Medicines must be stored properly, in a special place, away from light and heat sources, according to the temperature regime, which must be indicated by the manufacturer (in the refrigerator or at room temperature).

Medicines must be kept out of the reach of children.

An unknown medicine should not remain in the medicine cabinet. Each jar, box or sachet must be signed.

Medicines should not be used if they have expired.

Do not take drugs prescribed to another person: well tolerated by some, they can cause drug-induced illness (allergies) in others.

Strictly follow the rules for taking the drug: the time of admission (before or after meals), dosages and the interval between doses.

Take only those medicines that your doctor has prescribed for you.

Do not rush to start with medicines: sometimes it is enough to get enough sleep, rest, breathe fresh air.

Observing even these few and simple recommendations for the use of medicines, you can save the main thing - health!

Bibliographic list.

1) Alikberova L.Yu. Entertaining chemistry: A book for students, teachers and parents. – M.: AST-PRESS, 2002.

2) Artemenko A.I. The use of organic compounds. – M.: Bustard, 2005.

3) Mashkovsky M.D. Medicines. M.: Medicine, 2001.

4) Pichugina G.V. Chemistry and everyday life of a person. M.: Bustard, 2004.

5) Vidal's Handbook: Medicines in Russia: A Handbook.- M.: Astra-PharmService.- 2001.- 1536 p.

6) Tutelyan V.A. Vitamins: 99 questions and answers. - M. - 2000. - 47 p.

7) Encyclopedia for children, volume 17. Chemistry. - M. Avanta+, 200.-640s.

8) Register of Medicinal Products of Russia "Encyclopedia of Medicines". - 9th edition - LLC M; 2001.

9) Mashkovsky M.D. Medicines of the 20th century. M.: New wave, 1998, 320 p.;

10) Dyson G., May P. Chemistry of synthetic medicinal substances. Moscow: Mir, 1964, 660 p.

11) Encyclopedia of drugs 9 edition 2002. Medicines M.D. Mashkovsky 14th edition.

12) http:// www. consultpharma. en/ index. php/ en/ documents/ production/710- gostr-52249-2009- part1? showall=1

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Introduction

Description of the drug

Bibliography

Introduction

Among the tasks of pharmaceutical chemistry - such as modeling new drugs, drugs and their synthesis, the study of pharmacokinetics, etc., the analysis of the quality of drugs occupies a special place. The State Pharmacopoeia is a collection of mandatory national standards and regulations that normalize the quality of drugs.

Pharmacopoeial analysis of medicines includes quality assessment for a variety of indicators. In particular, the authenticity of the medicinal product is established, its purity is analyzed, and a quantitative determination is carried out. Initially, only chemical methods were used for such analysis; authenticity tests, impurity reactions and titration in quantitation.

Over time, not only has the level technical development pharmaceutical industry, but the requirements for the quality of medicines have also changed. IN last years there has been a trend towards a transition to the expanded use of physical and physical chemical methods analysis. In particular, spectral methods are widely used - infrared and ultraviolet spectrophotometry, nuclear magnetic resonance spectroscopy, etc. Chromatography methods (high-performance liquid, gas-liquid, thin-layer), electrophoresis, etc. are actively used.

The study of all these methods and their improvement is one of the most important tasks pharmaceutical chemistry today.

quality medicinal pharmacopoeial spectral

Methods of qualitative and quantitative analysis

The analysis of a substance can be carried out in order to establish its qualitative or quantitative composition. Accordingly, a distinction is made between qualitative and quantitative analysis.

Qualitative analysis allows you to establish what chemical elements the analyzed substance consists of and what ions, groups of atoms or molecules are included in its composition. When studying the composition of an unknown substance, a qualitative analysis always precedes a quantitative one, since the choice of a method for the quantitative determination of the constituent parts of the analyzed substance depends on the data obtained during its qualitative analysis.

Qualitative chemical analysis is mostly based on the transformation of the analyte into some new compound with characteristic properties: color, a certain physical state, crystalline or amorphous structure, a specific smell, etc. The chemical transformation that occurs in this case is called a qualitative analytical reaction , and the substances that cause this transformation are called reagents (reagents).

For example, to discover Fe +++ ions in a solution, the analyzed solution is first acidified with hydrochloric acid, and then a solution of potassium hexacyanoferrate (II) K4 is added. In the presence of Fe +++, a blue precipitate of iron hexacyanoferrate (II) Fe43 precipitates. (Prussian blue):

Another example of a qualitative chemical analysis is the detection of ammonium salts by heating the analyte with an aqueous solution of sodium hydroxide. Ammonium ions in the presence of OH- ions form ammonia, which is recognized by the smell or by the blue color of wet red litmus paper:

In the examples given, solutions of potassium hexacyanoferrate (II) and sodium hydroxide are, respectively, reagents for Fe+++ and NH4+ ions.

When analyzing a mixture of several substances with similar chemical properties, they are first separated and only then characteristic reactions are carried out for individual substances (or ions), therefore, qualitative analysis covers not only individual reactions for detecting ions, but also methods for their separation.

Quantitative analysis allows you to establish the quantitative ratio of the constituent parts of a given compound or mixture of substances. Unlike qualitative analysis, quantitative analysis makes it possible to determine the content of individual components of the analyte or the total content of the analyte in the test product.

Methods of qualitative and quantitative analysis, which allow determining the content of individual elements in the analyzed substance, are called elemental analysis; functional groups -- functional analysis; individual chemical compounds characterized by a certain molecular weight - molecular analysis.

A set of various chemical, physical and physicochemical methods for separating and determining individual structural (phase) components of heterogeneous! systems that differ in properties and physical structure and are limited from each other by interfaces are called phase analysis.

Methods for studying the quality of medicines

In accordance with the Global Fund XI methods of drug research are divided into physical, physico-chemical and chemical.

Physical methods. Include methods for determining the melting point, solidification, density (for liquid substances), refractive index (refractometry), optical rotation(polarimetry), etc.

Physical and chemical methods. They can be divided into 3 main groups: electrochemical (polarography, potentiometry), chromatographic and spectral (UV and IR spectrophotometry and photocolorimetry).

Polarography is a method for studying electrochemical processes based on establishing the dependence of the current strength on the voltage applied to the system under study. The electrolysis of the studied solutions is carried out in an electrolyzer, one of the electrodes of which is a dropping mercury electrode, and the auxiliary one is a mercury electrode with a large surface, the potential of which practically does not change when a current of low density passes. The resulting polarographic curve (polarogram) has the form of a wave. The exhaustion of the wave is related to the concentration of reactants. The method is used for the quantitative determination of many organic compounds.

Potentiometry - a method for determining pH and potentiometric titration.

Chromatography is the process of separation of mixtures of substances that occurs when they move in the flow of the mobile phase along the stationary sorbent. Separation occurs due to the difference in certain physico-chemical properties of the substances being separated, leading to their unequal interaction with the substance of the stationary phase, therefore, to a difference in the retention time of the sorbent layer.

According to the mechanism underlying the separation, there are adsorption, partition and ion-exchange chromatography. According to the method of separation and the equipment used, there are chromatography on columns, on paper in a thin layer of sorbent, gas and liquid chromatography, high performance liquid chromatography (HPLC), etc.

Spectral methods are based on the selective absorption of electromagnetic radiation by the analyzed substance. There are spectrophotometric methods based on the absorption of monochromatic UV and IR radiation by a substance, colorimetric and photocolorimetric methods based on the absorption of non-monochromatic radiation of the visible part of the spectrum by a substance.

Chemical methods. Based on the use of chemical reactions to identify drugs. For inorganic drugs, reactions to cations and anions are used, for organic drugs, to functional groups, while only such reactions are used that are accompanied by a visual external effect: a change in the color of the solution, the release of gases, precipitation, etc.

With the help of chemical methods, the numerical indicators of oils and esters are determined (acid number, iodine number, saponification number), characterizing their good quality.

Chemical methods for the quantitative analysis of medicinal substances include the gravimetric (weight) method, titrimetric (volumetric) methods, including acid-base titration in aqueous and non-aqueous media, gasometric analysis and quantitative elemental analysis.

gravimetric method. From inorganic medicinal substances, this method can be used to determine sulfates, converting them into insoluble barium salts, and silicates, after calcining them to silicon dioxide. It is possible to use gravimetry for the analysis of preparations of salts of quinine, alkaloids, some vitamins, etc.

titrimetric methods. This is the most common method in pharmaceutical analysis, characterized by low labor intensity and fairly high accuracy. Titrimetric methods can be subdivided into precipitation titrations, acid-base titrations, redox titrations, compleximetry, and nitritometry. With their help, a quantitative assessment is carried out by determining the individual elements or functional groups contained in the drug molecule.

Precipitation titration (argentometry, mercurimetry, mercurometry, etc.).

Acid - basic titration (titration in an aqueous medium, acidimetry - the use of acid as a titrant, alkalimetry - the use of alkali for titration, titration in mixed solvents, non-aqueous titration, etc.).

Redox titration (iodometry, iodochlorometry, bromatometry, permanganatometry, etc.).

Complexometry. The method is based on the formation of strong, water-soluble complexes of metal cations with Trilon B or other complexones. The interaction occurs in a stoichiometric ratio of 1:1, regardless of the charge of the cation.

Nitritometry. The method is based on the reactions of primary and secondary aromatic amines with sodium nitrite, which is used as a titrant. Primary aromatic amines form a diazo compound with sodium nitrite in an acidic medium, while secondary aromatic amines form nitroso compounds under these conditions.

Gasometric analysis. It has limited use in pharmaceutical analysis. The objects of this analysis are two gaseous preparations: oxygen and cyclopropane. The essence of the gasometric definition lies in the interaction of gases with absorption solutions.

Quantitative elemental analysis. This analysis is used for the quantitative determination of organic and organoelement compounds containing nitrogen, halogens, sulfur, as well as arsenic, bismuth, mercury, antimony, and other elements.

Biological methods of quality control of medicinal substances. The biological assessment of the quality of drugs is carried out according to their pharmacological activity or toxicity. Biological microbiological methods are used in cases where physical, chemical and physico-chemical methods cannot be used to conclude that the drug is good. Biological tests are carried out on animals cats, dogs, pigeons, rabbits, frogs, etc.), individual isolated organs (uterine horn, part of the skin) and cell groups (blood cells, strains of microorganisms, etc.). Biological activity is established, as a rule, by comparing the action of the test and standard samples.

Tests for microbiological purity are subjected to drugs that are not sterilized during the production process (tablets, capsules, granules, solutions, extracts, ointments, etc.). These tests are aimed at determining the composition and amount of microflora present in the LF. At the same time, compliance with the standards limiting microbial contamination (contamination) is established. The test includes the quantitative determination of viable bacteria and fungi, the identification of certain types of microorganisms, intestinal flora and staphylococci. The test is performed under aseptic conditions in accordance with the requirements of the Global Fund XI (v. 2, p. 193) by a two-layer agar method in Petri dishes.

The test for sterility is based on the proof of the absence of viable microorganisms of any kind in the drug and is one of the most important indicators of drug safety. All drugs for parenteral administration, eye drops, ointments, etc. are subjected to these tests. To control sterility, bioglycol and liquid Sabouraud medium are used, using the method of direct inoculation on nutrient media. If the drug has a pronounced antimicrobial effect or is poured into containers of more than 100 ml, then the membrane filtration method is used (GF, v. 2, p. 187).

Acidum acetylsalicylicum

Acetylsalicylic acid, or aspirin, is a salicylic ester of acetic acid.

Description. Colorless crystals or white crystalline powder, odorless, slightly acidic taste. In humid air, it gradually hydrolyzes to form acetic and salicylic acids. Slightly soluble in water, freely soluble in alcohol, soluble in chloroform, ether, in solutions of caustic and carbonic alkalis.

To thin the mass, chlorobenzene is added, the reaction mixture is poured into water, the separated acetylsalicylic acid is filtered off and recrystallized from benzene, chloroform, isopropyl alcohol, or other organic solvents.

In the finished preparation of acetylsalicylic acid, the presence of unbound salicylic acid residues is possible. The amount of salicylic acid as an impurity is regulated and the limit of the content of salicylic acid in acetylsalicylic acid is set by the State Pharmacopoeias of different countries.

The State Pharmacopoeia of the USSR, tenth edition of 1968, sets the permissible limit for the content of salicylic acid in acetylsalicylic acid to not more than 0.05% in the preparation.

Acetylsalicylic acid, when hydrolyzed in the body, breaks down into salicylic and acetic acids.

Acetylsalicylic acid as ester, formed by acetic acid and phenolic acid (instead of alcohol), is very easily hydrolyzed. Already when standing in moist air, it hydrolyzes into acetic and salicylic acids. In this regard, pharmacists often have to check whether acetylsalicylic acid has been hydrolyzed. For this, the reaction with FeCl3 is very convenient: acetylsalicylic acid does not give color with FeCl3, while salicylic acid, formed as a result of hydrolysis, gives a violet color.

Clinical and pharmacological Group: NSAIDs

Pharmacological action

Acetylsalicylic acid belongs to the group of acid-forming NSAIDs with analgesic, antipyretic and anti-inflammatory properties. The mechanism of its action is the irreversible inactivation of cyclooxygenase enzymes, which play an important role in the synthesis of prostaglandins. Acetylsalicylic acid in doses of 0.3 g to 1 g is used to relieve pain and conditions that are accompanied by mild fever, such as colds and flu, to reduce fever and relieve joint and muscle pain.

It is also used to treat acute and chronic inflammatory conditions such as rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis.

Acetylsalicylic acid inhibits platelet aggregation by blocking the synthesis of thromboxane A2 and is used in most vascular diseases in doses of 75-300 mg per day.

Indications

rheumatism;

rheumatoid arthritis;

infectious-allergic myocarditis;

fever in infectious and inflammatory diseases;

pain syndrome of low and medium intensity of various origins (including neuralgia, myalgia, headache);

prevention of thrombosis and embolism;

primary and secondary prevention of myocardial infarction;

prevention of cerebrovascular accidents by ischemic type;

in gradually increasing doses for prolonged "aspirin" desensitization and the formation of stable tolerance to NSAIDs in patients with "aspirin" asthma and the "aspirin triad".

Instruction on application And dosage

For adults, a single dose varies from 40 mg to 1 g, daily - from 150 mg to 8 g; frequency of use - 2-6 times a day. It is preferable to drink milk or alkaline mineral waters.

side action

nausea, vomiting;

anorexia;

pain in the epigastrium;

the occurrence of erosive and ulcerative lesions;

bleeding from the gastrointestinal tract;

dizziness;

headache;

reversible visual impairment;

noise in ears;

thrombocytopenia, anemia;

hemorrhagic syndrome;

prolongation of bleeding time;

impaired renal function;

acute renal failure;

skin rash;

angioedema;

bronchospasm;

"aspirin triad" (a combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid and pyrazolone drugs);

Reye's syndrome (Reynaud);

exacerbation of symptoms of chronic heart failure.

Contraindications

erosive and ulcerative lesions of the gastrointestinal tract in the acute phase;

gastrointestinal bleeding;

"aspirin triad";

a history of indications of urticaria, rhinitis caused by taking acetylsalicylic acid and other NSAIDs;

hemophilia;

hemorrhagic diathesis;

hypoprothrombinemia;

dissecting aortic aneurysm;

portal hypertension;

vitamin K deficiency;

hepatic and / or renal failure;

deficiency of glucose-6-phosphate dehydrogenase;

Reye's syndrome;

children's age (up to 15 years - the risk of developing Reye's syndrome in children with hyperthermia on the background of viral diseases);

1st and 3rd trimesters of pregnancy;

lactation period;

hypersensitivity to acetylsalicylic acid and other salicylates.

Special instructions

Use with caution in patients with diseases of the liver and kidneys, with bronchial asthma, erosive and ulcerative lesions and bleeding from the gastrointestinal tract in history, with increased bleeding or while conducting anticoagulant therapy, decompensated chronic heart failure.

Acetylsalicylic acid, even in small doses, reduces the excretion of uric acid from the body, which can cause an acute attack of gout in predisposed patients. When conducting long-term therapy and / or the use of acetylsalicylic acid in high doses, medical supervision and regular monitoring of hemoglobin levels are required.

The use of acetylsalicylic acid as an anti-inflammatory agent in a daily dose of 5-8 grams is limited due to the high likelihood of side effects from the gastrointestinal tract.

Before surgery, to reduce bleeding during surgery and in the postoperative period, salicylates should be discontinued 5-7 days in advance.

During long-term therapy, it is necessary to conduct a complete blood count and a study of feces for occult blood.

The use of acetylsalicylic acid in pediatrics is contraindicated, since in the case of a viral infection in children under the influence of acetylsalicylic acid, the risk of developing Reye's syndrome increases. Symptoms of Reye's syndrome are prolonged vomiting, acute encephalopathy, liver enlargement.

The duration of treatment (without consulting a doctor) should not exceed 7 days when prescribed as an analgesic and more than 3 days as an antipyretic.

During the treatment period, the patient should refrain from drinking alcohol.

The form release, composition And package

Tablets 1 tab.

acetylsalicylic acid 325 mg

30 - containers (1) - packs.

50 - containers (1) - packs.

12 - blisters (1) - packs.

Pharmacopoeia article. experimental part

Description. Colorless crystals or white crystalline powder, odorless or with a slight odor, slightly acidic taste. The drug is stable in dry air, in humid air it gradually hydrolyzes with the formation of acetic and salicylic acids.

Solubility. Slightly soluble in water, freely soluble in alcohol, soluble in chloroform, ether, in solutions of caustic and carbonic alkalis.

Authenticity. 0 5 g of the drug is boiled for 3 minutes with 5 ml of sodium hydroxide solution, then cooled and acidified with diluted sulfuric acid; a white crystalline precipitate is released. The solution is poured into another test tube and 2 ml of alcohol and 2 ml of concentrated sulfuric acid are added to it; the solution has the smell of acetic ethyl ether. Add 1-2 drops of ferric chloride solution to the precipitate; a purple color appears.

0.2 g of the drug is placed in a porcelain cup, 0.5 ml of concentrated sulfuric acid is added, mixed and 1-2 drops of water are added; there is a smell of acetic acid. Then add 1-2 drops of formalin; a pink color appears.

Melting point 133-138° (temperature rise rate 4-6° per minute).

Chlorides. 1.5 g of the drug is shaken with 30 ml of water and filtered. 10 ml of the filtrate must pass the chloride test (no more than 0.004% in the preparation).

sulfates. 10 ml of the same filtrate must pass the sulfate test (not more than 0.02% in the preparation).

organic impurities. 0.5 g of the drug is dissolved in 5 ml of concentrated sulfuric acid; the color of the solution should not be more intense than standard No. 5a.

free salicylic acid. 0.3 g of the drug is dissolved in 5 ml of alcohol and 25 ml of water are added (test solution). 15 ml of this solution are placed in one cylinder, 5 ml of the same solution are placed in the other. 0.5 ml 0.01% aqueous solution salicylic acid, 2 ml alcohol and dilute to 15 ml with water (standard solution). Then, 1 ml of an acidic 0.2% solution of iron ammonium alum is added to both cylinders.

The color of the test solution should not be more intense than the reference solution (no more than 0.05% in the preparation).

Sulfate ash And heavy metals. Sulphated ash from 0.5 g of the preparation should not exceed 0.1% and must pass the test for heavy metals (not more than 0.001% in the preparation).

quantitative definition. About 0.5 g of the drug (accurately weighed) is dissolved in 10 ml of alcohol neutralized by phenolphthalein (5-6 drops) and cooled to 8-10 °. The solution is titrated with the same indicator 0.1 N. sodium hydroxide solution until pink.

1 ml 0.1 n. sodium hydroxide solution corresponds to 0.01802 g of C9H8O4 which should be at least 99.5% in the preparation.

Storage. In a well sealed container.

Antirheumatic, anti-inflammatory, analgesic, antipyretic.

Pharmaceutical chemistry is a science that, based on the general laws of chemical sciences, explores the methods of obtaining, structure, physical and chemical properties of medicinal substances, the relationship between their chemical structure and effect on the body; methods of quality control of medicines and changes occurring during their storage.

The main methods for the study of medicinal substances in pharmaceutical chemistry are analysis and synthesis - dialectically closely related processes that complement each other. Analysis and synthesis are powerful means of understanding the essence of phenomena occurring in nature.

The tasks facing pharmaceutical chemistry are solved using classical physical, chemical and physicochemical methods, which are used both for the synthesis and for the analysis of medicinal substances.

To learn pharmaceutical chemistry, the future pharmacist must have deep knowledge in the field of general theoretical chemical and biomedical disciplines, physics, and mathematics. Strong knowledge in the field of philosophy is also necessary, because pharmaceutical chemistry, like other chemical sciences, deals with the study of the chemical form of the motion of matter.

Pharmaceutical chemistry occupies a central place among other special pharmaceutical disciplines - pharmacognosy, drug technology, pharmacology, organization and economics of pharmacy, toxicological chemistry and is a kind of link between them.

At the same time, pharmaceutical chemistry occupies an intermediate position between the complex of biomedical and chemical sciences. The object of application of drugs is the body of a sick person. The study of the processes occurring in the body of a sick person and its treatment are carried out by specialists working in the field of clinical medical sciences (therapy, surgery, obstetrics and gynecology, etc.), as well as theoretical medical disciplines: anatomy, physiology, etc. in drug medicine requires the joint work of a doctor and a pharmacist in the treatment of a patient.

Being an applied science, pharmaceutical chemistry is based on the theory and laws of such chemical sciences as inorganic, organic, analytical, physical, colloidal chemistry. In close connection with inorganic and organic chemistry Pharmaceutical chemistry deals with the study of methods for the synthesis of drugs. Since their effect on the body depends on both the chemical structure and physico-chemical properties, pharmaceutical chemistry uses the laws of physical chemistry.

When developing methods for quality control of drugs and dosage forms in pharmaceutical chemistry, methods of analytical chemistry are used. However, pharmaceutical analysis has its own specific features and includes three mandatory steps: establishing the authenticity of the drug, controlling its purity (setting acceptable limits for impurities) and quantifying the drug substance.

The development of pharmaceutical chemistry is also impossible without the widespread use of the laws of such exact sciences as physics and mathematics, since without them it is impossible to know the physical methods of studying medicinal substances and the various methods of calculation used in pharmaceutical analysis.

Pharmaceutical analysis uses a variety of research methods: physical, physico-chemical, chemical, biological. The use of physical and physico-chemical methods requires appropriate instruments and instruments, therefore, these methods are also called instrumental, or instrumental.

The use of physical methods is based on measurement physical constants, for example, transparency or degree of turbidity, color, humidity, melting point, solidification and boiling point, etc.

With the help of physicochemical methods, the physical constants of the analyzed system are measured, which change as a result of chemical reactions. This group of methods includes optical, electrochemical, chromatographic.

Chemical methods of analysis are based on the performance of chemical reactions.

Biological control of medicinal substances is carried out on animals, individual isolated organs, groups of cells, on certain strains of microorganisms. Establish the strength of the pharmacological effect or toxicity.

Methods used in pharmaceutical analysis should be sensitive, specific, selective, fast and suitable for rapid analysis in a pharmacy setting.

Bibliography

1. Pharmaceutical chemistry: Proc. allowance / Ed. L.P. Arzamastsev. M.: GEOTAR-MED, 2004.

2. Pharmaceutical analysis of drugs / Under the general editorship of V.A.

3. Shapovalova. Kharkov: IMP "Rubicon", 1995.

4. Melent'eva G.A., Antonova L.A. Pharmaceutical chemistry. M.: Medicine, 1985.

5. Arzamastsev A.P. pharmacopoeial analysis. M.: Medicine, 1971.

6. Belikov V.G. Pharmaceutical chemistry. In 2 parts. Part 1. General pharmaceutical chemistry: Proc. for pharmaceutical in-tov and faculty. honey. in-comrade. M.: Higher. school, 1993.

7. State Pharmacopoeia Russian Federation, X edition - under. ed. Yurgel N.V. Moscow: "Scientific Center for Expertise of Medicinal Products". 2008.

8. International Pharmacopoeia, Third Edition, V.2. World Health Organization. Geneva. 1983, 364 p.

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One of the most important tasks of pharmaceutical chemistry is the development and improvement of methods for assessing the quality of medicines.

To establish the purity of medicinal substances, various physical, physico-chemical, chemical methods of analysis or a combination of them are used.

The GF offers the following methods of drug quality control.

Physical and physico-chemical methods. These include: determination of melting and solidification temperatures, as well as temperature limits of distillation; determination of density, refractive indices (refractometry), optical rotation (polarimetry); spectrophotometry - ultraviolet, infrared; photocolorimetry, emission and atomic absorption spectrometry, fluorimetry, nuclear magnetic resonance spectroscopy, mass spectrometry; chromatography - adsorption, distribution, ion-exchange, gas, high-performance liquid; electrophoresis (frontal, zonal, capillary); electrometric methods (potentiometric determination of pH, potentiometric titration, amperometric titration, voltammetry).

In addition, it is possible to use methods that are alternative to pharmacopoeial methods, which sometimes have more advanced analytical characteristics (speed, accuracy of analysis, automation). In some cases, a pharmaceutical company purchases a device based on a method not yet included in the Pharmacopoeia (for example, the method of Raman spectroscopy - optical dichroism). Sometimes it is advisable to replace the chromatographic method with a spectrophotometric one when determining the authenticity or testing for purity. The pharmacopoeial method for determining heavy metal impurities by precipitating them in the form of sulfides or thioacetamides has a number of disadvantages. To determine heavy metal impurities, many manufacturers are implementing such physicochemical methods of analysis as atomic absorption spectrometry and inductively coupled plasma atomic emission spectrometry.

An important physical constant that characterizes the authenticity and degree of purity of drugs is the melting point. A pure substance has a distinct melting point, which changes in the presence of impurities. For medicinal substances containing a certain amount of admissible impurities, the GF regulates the melting temperature range within 2 °C. But in accordance with Raoult's law (AT = iK3C, where AT is the decrease in the crystallization temperature; K3 is the cryoscopic constant; C is the concentration) at i = 1 (non-electrolyte), the value of AG cannot be the same for all substances. This is connected not only with the content of impurities, but also with the nature of the drug itself, i.e., with the value of the cryoscopic constant K3, which reflects the molar decrease in the melting point of the drug. Thus, at the same AT = 2 °C for camphor (K3 = 40) and phenol (K3 = 7.3), the mass fractions of impurities are not equal and amount to 0.76 and 2.5%, respectively.

For substances that melt with decomposition, the temperature at which the substance decomposes and a sharp change in its appearance occurs is usually indicated.

In some private articles of GF X, it is recommended to determine the solidification point or boiling point (according to GF XI - “distillation temperature limits”) for a number of liquid drugs. The boiling point should be within the interval given in the private article.

A wider interval indicates the presence of impurities.

In many private articles of GF X, permissible values ​​\u200b\u200bof density, less often viscosity, are given, confirming the authenticity and good quality of drugs.

Almost all private articles of SP X normalize such an indicator of the quality of drugs as solubility in various solvents. The presence of impurities in a drug can affect its solubility, decreasing or increasing it, depending on the nature of the impurity.

The purity criteria are also the color of the drug and / or the transparency of liquid dosage forms.

Physical constants such as the refractive index of a light beam in a solution of the test substance (refractometry) and the specific rotation due to the ability of a number of substances or their solutions to rotate the polarization plane when plane polarized light passes through them (polarimetry) can serve as a certain criterion for the purity of a drug. Methods for determining these constants are related to optical methods of analysis and are also used to establish the authenticity and quantitative analysis of drugs and their dosage forms.

An important criterion for the good quality of a number of drugs is their water content. A change in this indicator (especially during storage) can change the concentration of the active substance, and, consequently, the pharmacological activity and make the drug unsuitable for use.

Chemical methods. These include: qualitative tests for authenticity, solubility, determination of volatile substances and water, determination of the nitrogen content in organic compounds, titrimetric methods (acid-base titration, titration in non-aqueous solvents, complexometry), nitritemetry, acid number, saponification number, ether number, iodine number, etc.

biological methods. Biological methods of drug quality control are very diverse. Among them are tests for toxicity, sterility, microbiological purity.

To conduct physical and chemical analysis of intermediates, drug substances and finished dosage forms, when checking their quality for compliance with the requirements of the FS, the control and analytical laboratory must be equipped with the following minimum set of equipment and instruments:

IR spectrophotometer (to determine authenticity);

spectrophotometer for spectrometry in the visible and UV region (determination of authenticity, quantitative determination, dosing uniformity, solubility);

equipment for thin layer chromatography (TLC) (determination of authenticity, related impurities);

chromatograph for high performance liquid chromatography (HPLC) (authentication, quantitation, determination of related impurities, dosing uniformity, solubility);

gas-liquid chromatograph (GLC) (content of impurities, determination of dosing uniformity);

polarimeter (determination of authenticity, quantitative determination);

potentiometer (pH measurement, quantitative determination);

atomic absorption spectrophotometer (elemental analysis of heavy metals and non-metals);

K. Fischer titrator (determination of water content);

derivatograph (determination of weight loss upon drying).

4.2 Optical methods

This group includes methods based on determining the refractive index of a light beam in a solution of the test substance (refractometry), measuring the interference of light (interferometry), and the ability of a substance solution to rotate the plane of a polarized beam (polarimetry).

Optical methods are increasingly used in the practice of intra-pharmacy control due to the rapidity, the minimum consumption of the analyzed drugs.

Refractometry is used to test the authenticity of medicinal substances that are liquids (nicotinic acid diethylamide, methyl salicylate, tocopherol acetate), and in intra-pharmacy control - to analyze dosage forms, including double and triple mixtures. Volumetric refractometric analysis and refractometric analysis by the method of complete and incomplete extraction are also used.

Various variants of methods for the analysis of drugs, titrated solutions, and distilled water by the interferometric method have been developed.

Polarimetry is used to test the authenticity of drugs whose molecules contain an asymmetric carbon atom. Among them, most drugs from the groups of alkaloids, hormones, vitamins, antibiotics, terpenes.

In analytical chemistry and pharmaceutical analysis, X-ray refractometry of powders, spectropolarimetric analysis, laser interferometry, rotational dispersion and circular dichroism are used.

In addition to the indicated optical methods, chemical microscopy does not lose its significance for the identification of individual medicinal substances in pharmaceutical and toxicological analysis. The use of electron microscopy is promising, especially in phytochemical analysis. Unlike optical microscopy, the object is exposed to a high-energy electron beam. The image formed by scattered electrons is observed on a fluorescent screen.

One of the promising express physical methods is X-ray analysis. It allows you to identify medicinal substances in crystalline form and to distinguish at the same time their polymorphic state. For the analysis of crystalline medicinal substances, various types of microscopy and methods such as Auger spectrometry, photoacoustic spectroscopy, computed tomography, radioactivity measurements, etc. can also be used.

An effective non-destructive method is reflective infrared spectroscopy, which is used to determine the impurities of various decomposition products and water, as well as in the analysis of multicomponent mixtures.

4.3 Absorption methods

Absorption methods are based on the properties of substances to absorb light in different regions of the spectrum.

Atomic absorption spectrophotometry is based on the use of ultraviolet or visible radiation resonant frequency. Absorption of radiation is caused by the transition of electrons from the outer orbitals of atoms to orbitals with more high energy. Objects that absorb radiation are gaseous atoms, as well as some organic substances. The essence of determinations by the method of atomic absorption spectrometry is that through the flame in which the analyzed sample solution is sprayed, resonant radiation from a lamp with a hollow cathode passes. This radiation enters the entrance slit of the monochromator, and only the resonant line of the element under test stands out from the spectrum. The photoelectric method measures the decrease in the intensity of the resonance line, which occurs as a result of its absorption by the atoms of the element being determined. The concentration is calculated using an equation that reflects its dependence on the attenuation of the radiation intensity of the light source, the length of the absorbing layer and the light absorption coefficient at the center of the absorption line. The method is characterized by high selectivity and sensitivity.

The absorption of resonance lines is measured on atomic absorption spectrophotometers of the Spektr-1, Saturn, and other types. This indicates the high sensitivity of the method. It is increasingly used to assess the purity of drugs, in particular the determination of the minimum impurities of heavy metals. The use of atomic absorption spectrophotometry is promising for the analysis of multivitamin preparations, amino acids, barbiturates, some antibiotics, alkaloids, halogen-containing drugs, and mercury-containing compounds.

It is also possible to use X-ray absorption spectroscopy in pharmacy, based on the absorption of X-ray radiation by atoms.

Ultraviolet spectrophotometry is the simplest and most widely used absorption method in pharmacy. It is used at all stages of the pharmaceutical analysis of drugs (tests of authenticity, purity, quantification). A large number of methods have been developed for the qualitative and quantitative analysis of dosage forms by ultraviolet spectrophotometry. For identification, atlases of the spectra of medicinal substances can be used, which systematize information about the nature of the spectral curves and the values ​​of specific absorption indices.

There are various options for using the method of UV spectrophotometry for identification. Authenticity tests identify medicinal substances by position maximum light absorption. More often in pharmacopoeial articles, the positions of the maximum (or minimum) and the corresponding values ​​of optical densities are given. Sometimes a method is used based on calculating the ratio of optical densities at two wavelengths (they usually correspond to two maxima or a maximum and minimum of light absorption). A number of medicinal substances are also identified by the specific absorption rate of the solution.

The use of such optical characteristics as the position of the absorption band in the wavelength scale, the frequency at the absorption maximum, the value of the peak and integral intensity, the half-width and asymmetry of the bands, and the strength of the oscillator are very promising for the identification of medicinal substances. These parameters make the identification of substances more reliable than the determination of the wavelength of the maximum light absorption and the specific absorption index. These constants, which make it possible to characterize the presence of a relationship between the UV spectrum and the structure of the molecule, were established and used to assess the quality of medicinal substances containing an oxygen heteroatom in the molecule (V.P. Buryak).

An objective choice of the optimal conditions for quantitative spectrophotometric analysis can only be carried out by a preliminary study of the ionization constants, the influence of the nature of solvents, the pH of the medium, and other factors on the nature of the absorption spectrum.

The NTD provides various ways to use UV spectrophotometry for the quantitative determination of medicinal substances that are vitamins (retinol acetate, rutin, cyanocobalamin), steroid hormones(cortisone acetate, prednisone, pregnin, testosterone propionate), antibiotics (sodium salts of oxacillin and methicillin, phenoxymethylpecillin, chloramphenicol stearate, griseofulvin). The solvents for spectrophotometric measurements are usually water or ethanol. The calculation of the concentration is carried out in various ways: according to the standard, specific absorption index or calibration curve.

Quantitative spectrophotometric analysis should be combined with UV identification. In this case, a solution prepared from one sample can be used for both of these tests. Most often, in spectrophotometric determinations, a method is used based on a comparison of the optical densities of the analyzed and standard solutions. Certain conditions of analysis require medicinal substances that can form acid-base forms depending on the pH of the medium. In such cases, it is necessary to first select the conditions under which the substance in solution will be completely in one of these forms.

To reduce the relative error of photometric analysis, in particular, to reduce the systematic error, it is very promising to use standard samples of medicinal substances. Considering the difficulty of obtaining and high cost, they can be replaced by standards prepared from available inorganic compounds (potassium dichromate, potassium chromate).

In SP XI, the field of application of UV spectrophotometry has been expanded. The method is recommended for the analysis of multicomponent systems, as well as for the analysis of drugs that themselves do not absorb light in the ultraviolet and visible regions of the spectrum, but can be converted into light-absorbing compounds using various chemical reactions.

Differential methods make it possible to expand the field of application of photometry in pharmaceutical analysis. They make it possible to increase its objectivity and accuracy, as well as to analyze high concentrations of substances. In addition, these methods can be used to analyze multicomponent mixtures without preliminary separation.

The method of differential spectrophotometry and photocolorimetry is included in the SP XI, no. 1 (p. 40). Its essence lies in measuring the light absorption of the analyzed solution relative to the reference solution containing a certain amount of the test substance. This leads to a change in the working area of ​​the instrument scale and a decrease in the relative analysis error to 0.5–1%, i.e. the same as for titrimetric methods. Good results were obtained when using neutral color filters with known optical density instead of reference solutions; spectrophotometers and photocolorimeters included in the set (V.G.Belikov).

The differential method has found application not only in spectrophotometry and photocolorimetry, but also in phototurbidimetry, photonephelometry, and interferometry. Differential methods can be extended to other physicochemical methods. The methods of chemical differential analysis based on the use of such chemical influences on the state of a drug substance in solution as a change in the pH of the medium, a change in the solvent, a change in temperature, the influence of electric, magnetic, ultrasonic fields, etc., also have great prospects for the analysis of drugs.

One of the variants of differential spectrophotometry, the ΔE method, opens up wide possibilities in quantitative spectrophotometric analysis. It is based on the transformation of the analyte into a tautomeric (or other) form, which differs in the nature of light absorption.

New opportunities in the field of identification and quantification organic matter opens up the use of derivative UV spectrophotometry. The method is based on the selection of individual bands from UV spectra, which are the sum of overlapping absorption bands or bands that do not have a clearly defined absorption maximum.

Derivative spectrophotometry makes it possible to identify medicinal substances similar in chemical structure or mixtures thereof. To increase the selectivity of qualitative spectrophotometric analysis, a method for constructing second derivatives of UV spectra is used. The second derivative can be calculated by numerical differentiation.

A unified method for obtaining derivatives of absorption spectra has been developed, which takes into account the features of the nature of the spectrum. It is shown that the second derivative has a resolution approximately 1.3 times greater than that of direct spectrophotometry. This made it possible to use this method for the identification of caffeine, theobromine, theophylline, papaverine hydrochloride and dibazole in dosage forms. The second and fourth derivatives are more effective in quantitative analysis compared to titrimetric methods. The duration of the determination is reduced by 3-4 times. The determination of these preparations in mixtures turned out to be possible regardless of the nature of the absorption of accompanying substances or with a significant decrease in the effect of their light absorption. This eliminates time-consuming operations for the separation of mixtures.

The use of a combined polynomial in spectrophotometric analysis made it possible to exclude the influence of a nonlinear background and develop methods for the quantitative determination of a number of drugs in dosage forms that do not require complex calculations of the analysis results. The combined polynomial has been successfully used in the study of processes occurring during the storage of medicinal substances and in chemical and toxicological studies, as it allows to reduce the effect of light-absorbing impurities (E.N. Vergeichik).

Raman spectroscopy (Raman spectroscopy) differs from other spectroscopic methods in sensitivity, a large choice of solvents, and temperature ranges. The presence of a domestic Raman spectrometer of the DSF-24 brand makes it possible to use this method not only for determining the chemical structure, but also in pharmaceutical analysis.

The method of spectrophotometric titration has not yet received due development in the practice of pharmaceutical analysis. This method makes it possible to perform indicator-free titration of multicomponent mixtures with close values RK based on the successive change in optical density during the titration process depending on the volume of the added titrant.

The photocolorimetric method is widely used in pharmaceutical analysis. Quantification by this method, in contrast to UV spbktrofotometry carried out in the visible region of the spectrum. The substance to be determined is converted into a colored compound with the help of some reagent, and then the color intensity of the solution is measured on a photocolorimeter. The accuracy of determinations depends on the choice of optimal conditions for the course of a chemical reaction.

Methods for the analysis of preparations derived from primary aromatic amines based on the use of diazotization and azo coupling reactions are widely used in photometric analysis. Widely used as an azo component N-(1-naphthyl)-ethylenediamine. The azo dye formation reaction underlies the photometric determination of many preparations derived from phenols.

The photocolorimetric method is included in the NTD for the quantitative determination of a number of nitro derivatives (nitroglycerin, furadonin, furazolidone), as well as vitamin preparations (riboflavin, folic acid) and cardiac glycosides (celanide). Numerous methods have been developed for the photocolorimetric determination of drugs in dosage forms. There are various modifications of photocolorimetry and methods for calculating the concentration in photocolorimetric analysis.

Polycarbonyl compounds such as bindone (anhydro-bis-indanedione-1,3), alloxan (tetraoxohexa-hydropyrimidine), sodium salt of 2-carbethoxyindanedione-1,3 and some of its derivatives proved to be promising for use as color reagents in photometric analysis. Optimal conditions have been established and unified methods for the identification and spectrophotometric determination in the visible region of medicinal substances containing a primary aromatic or aliphatic amino group, a sulfonyl urea residue or being nitrogen-containing organic bases and their salts have been developed (V.V. Petrenko).

Widely used in photocolorimetry are staining reactions based on the formation of polymethine dyes, which are obtained by breaking the pyridine or furan rings or by some condensation reactions with primary aromatic amines (A.S. Beisenbekov).

For identification and spectrophotometric determination in the visible region of the spectrum of medicinal substances, derivatives of aromatic amines, thiols, thioamides and other mercapto compounds were used as color reagents N-chlorine-, N-benzenesulfonyl- and N-benzenesulfonyl-2-chloro-1,4-benzoquinone imine.

One of the options for unifying the methods of photometric analysis is based on indirect determination by the residue of sodium nitrite introduced into the reaction mixture in the form of a standard solution taken in excess. The excess nitrite is then determined photometrically by a diazotization reaction with ethacridine lactate. This technique is used for indirect photometric determination of nitrogen-containing medicinal substances by the nitrite ion formed as a result of their transformations (hydrolysis, thermal decomposition). The unified methodology allows for quality control of more than 30 such medicinal substances in numerous dosage forms (P.N. Ivakhnenko).

Phototurbidimetry and photonephelometry are methods that have great potential, but are still of limited use in pharmaceutical analysis. Based on the measurement of light absorbed (turbidimetry) or scattered (nephelometry) by suspended particles of the analyte. Every year the methods are improved. Recommend, for example, chronophototurbidimetry in the analysis of medicinal substances. The essence of the method is to establish changes in light extinguishing over time. Also described is the use of thermonephelometry, based on establishing the dependence of the concentration of a substance on the temperature at which the drug solution becomes cloudy.

Systematic studies in the field of phototurbidimetry, chronophototurbidimetry and phototurbidimetric titration have shown the possibility of using phosphotungstic acid for the quantitative determination of nitrogen-containing drugs. In phototurbidimetric analysis, both direct and differential methods were used, as well as automatic phototurbidimetric titration and chronophototurbidimetric determination of two-component dosage forms (A.I. Sichko).

Infrared (IR) spectroscopy is characterized by a wide information content, which creates the possibility of an objective assessment of the authenticity and quantitative determination of medicinal substances. The IR spectrum unambiguously characterizes the entire structure of the molecule. Differences in chemical structure change the nature of the IR spectrum. Important advantages of IR spectrophotometry are specificity, speed of analysis, high sensitivity, objectivity of the results obtained, and the possibility of analyzing a substance in a crystalline state.

IR spectra are measured using usually suspensions of drugs in liquid paraffin, the intrinsic absorption of which does not interfere with the identification of the analyte. To establish authenticity, as a rule, the so-called "fingerprint" region (650-1500 cm -1), located in the frequency range from 650 to 1800 cm -1, as well as stretching vibrations of chemical bonds

C=0, C=C, C=N

SP XI recommends two methods for establishing the authenticity of medicinal substances using IR spectra. One of them is based on a comparison of the IR spectra of the test substance and its standard sample. The spectra must be taken under identical conditions, i.e. the samples must be in the same state of aggregation, in the same concentration, the registration rate must be the same, etc. The second method is to compare the IR spectrum of the test substance with its standard spectrum. In this case, it is necessary to strictly observe the conditions provided for the removal of the standard spectrum, given in the relevant NTD (GF, VFS, FS). The complete coincidence of the absorption bands indicates the identity of the substances. However, polymorphic modifications can give different IR spectra. In this case, to confirm the identity, it is necessary to recrystallize the test substances from the same solvent and take the spectra again.

Absorption intensity can also serve as a confirmation of the authenticity of a medicinal substance. For this purpose, such constants as the absorption index or the value of the integrated absorption intensity, equal to the area that the curve envelops in the absorption spectrum, are used.

The possibility of using IR spectroscopy to identify a large group of medicinal substances containing carbonyl groups in the molecule has been established. Authenticity is established by the characteristic absorption bands in the following areas: 1720-1760, 1424-1418, 950-00 cm -1 for carboxylic acids; 1596-1582, 1430-1400, 1630-1612, 1528-1518 cm -1 for amino acids; 1690-1670, 1615-1580 cm -1 for amides; 1770--1670 cm -1 for derivatives of barbituric acid; 1384-1370, 1742-1740, 1050 cm -1 for terpenoids; 1680-1540, 1380-1278 cm -1 for tetracycline antibiotics; 3580-3100, 3050-2870, 1742-1630, 903-390 cm -1 for steroids (A.F. Mynka).

The method of IR spectroscopy is included in the pharmacopoeias of many foreign countries and in MF III, where it is used to identify more than 40 medicinal substances. IR spectrophotometry can be used not only to quantify medicinal substances, but also to study such chemical transformations as dissociation, solvolysis, metabolism, polymorphism, etc.

4.4 Methods based on emission of radiation

This group of methods includes flame photometry, fluorescent and radiochemical methods.

SP XI includes emission and flame spectrometry for the purposes of qualitative and quantitative determination of chemical elements and their impurities in medicinal substances. Measurement of the radiation intensity of the spectral lines of the tested elements is performed on domestic flame photometers PFL-1, PFM, PAZH-1. The recording systems are photocells associated with digital and printing devices. The accuracy of determinations by methods of emission, as well as atomic absorption, flame spectrometry is within 1--4%, the detection limit can reach 0.001 μg/ml.

Quantitative determination of elements by flame emission spectrometry (flame photometry) is based on establishing the relationship between the intensity of the spectral line and the concentration of the element in solution. The essence of the test is to spray the analyzed solution to the state of an aerosol in a burner flame. Under the influence of the flame temperature, evaporation of the solvent and solid particles from aerosol droplets, dissociation of molecules, excitation of atoms and the appearance of their characteristic radiation occur. With the help of a light filter or a monochromator, the radiation of the analyzed element is separated from the others and, falling on the photocell, causes a photocurrent, which is measured using a galvanometer or potentiometer.

Flame photometry has been used for the quantitative analysis of sodium-, potassium- and calcium-containing drugs in dosage forms. Based on the study of the influence on the emission of determined cations, organic anions, auxiliary and accompanying components, methods were developed for the quantitative determination of sodium bicarbonate, sodium salicylate, PASA-sodium, bylignost, hexenal, sodium nucleinate, calcium chloride and gluconate, bepaska, etc. Methods for the simultaneous determination of two salts with different cations in dosage forms, for example, potassium iodide - sodium bicarbonate, calcium chloride - potassium bromide, potassium iodide - sodium salicylate, etc.

Luminescent methods are based on the measurement of secondary radiation resulting from the action of light on the analyte. These include fluorescent methods, chemiluminescence, X-ray fluorescence, etc.

Fluorescent methods are based on the ability of substances to fluoresce in UV light. This ability is due to the structure of either the organic compounds themselves or the products of their dissociation, solvolysis and other transformations caused by the action of various reagents.

Fluorescent properties are usually possessed by organic compounds with a symmetrical molecular structure, in which there are conjugated bonds, nitro-, nitroso-, azo-, amido-, carboxyl or carbonyl groups. Fluorescence intensity depends on the chemical structure and concentration of the substance, as well as other factors.

Fluorimetry can be used for both qualitative and quantitative analysis. Quantitative analysis is performed on spectrofluorimeters. The principle of their operation is that the light from a mercury-quartz lamp falls through a primary light filter and a condenser onto a cuvette with a solution of the test substance. The calculation of the concentration is carried out on a scale of standard samples of a fluorescent substance of known concentration.

Unified methods have been developed for the quantitative spectrofluorimetric determination of p-aminobenzenesulfamide derivatives (streptocid, sodium sulfacyl, sulgin, urosulfan, etc.) and p-aminobenzoic acid (anesthesin, novocaine, novocainamide). Aqueous-alkaline solutions of sulfonamides have the highest fluorescence at pH b--8 and 10--12. In addition, sulfonamides containing an unsubstituted primary aromatic amino group in the molecule, after heating with o-phthalaldehyde in the presence of sulfuric acid, acquire intense fluorescence in the region of 320–540 nm. Barbituric acid derivatives (barbital, barbital sodium, phenobarbital, etaminal sodium) fluoresce in the same region. alkaline environment(pH 12--13) with a fluorescence maximum at 400 nm. Highly sensitive and specific methods for the spectrofluorimetric determination of antibiotics were proposed: tetracycline, oxytetracycline hydrochloride, streptomycin sulfate, passomycin, florimycin sulfate, griseofulvin and cardiac glycoside celanide (F.V. Babilev). Studies of the fluorescence spectra of a number of drugs containing natural compounds: derivatives of coumarin, anthraquinone, flavonoids were carried out (V.P. Georgievsky).

Complex-forming groups have been identified in 120 medicinal substances, derivatives of oxybenzoic, hydroxynaphthoic, anthranilic acids, 8-hydroxyquinoline, oxypyridine, 3- and 5-hydroxyflavone, pteridine, etc. These groups are capable of forming fluorescent complexes with magnesium, aluminum, boron, zinc, scandium cations upon excitation of fluorescence from 330 nm and above and its emission at wavelengths exceeding 400 nm. The studies carried out made it possible to develop methods for fluorimetry of 85 drugs (A.A. Khabarov).

Along with derivative spectrophotometry in pharmaceutical analysis, the possibility of using derivative spectrofluorimetry has been substantiated. The spectra are taken on an MPF-4 fluorescent spectrophotometer with a thermostatic cell, and the derivatives are found by analogous differentiation using a computer. The method was used to develop simple, accurate and highly sensitive methods for the quantitative determination of pyridoxine and ephedrine hydrochlorides in dosage forms in the presence of degradation products.

Perspective of use x-ray fluorescence for the determination of small amounts of impurities in medicinal products due to high sensitivity and the ability to perform analysis without prior destruction of the substance. Method X-ray fluorescence spectrometry turned out to be promising for the quantitative analysis of substances that have heteroatoms such as iron, cobalt, bromine, silver, etc. in the molecule. The principle of the method is to compare the secondary X-ray radiation of the element in the analyzed and standard sample. X-ray fluorescence spectrometry is one of the methods that do not require preliminary destructive changes. The analysis is carried out on a domestic RS-5700 spectrometer. The duration of the analysis is 15 min.

Chemiluminescence is a method that uses the energy generated during chemical reactions.

This energy serves as a source of excitation. It is emitted during oxidation by some barbiturates (especially phenobarbital), aromatic acid hydrazides and other compounds. This creates great opportunities for using the method to determine very low concentrations of substances in biological material.

Radiochemical methods are increasingly used in pharmaceutical analysis. Radiometric analysis, based on the measurement of? - or? - radiation using spectrometers, is used (along with other parameters to assess the quality of pharmacopoeial radioactive preparations. Highly sensitive methods of analysis using radioactive isotopes (labeled atoms) are widely used in various fields of technology, and especially in analytical chemistry ).To detect traces of impurities in substances, activation analysis is used; to determine in mixtures of difficult-to-separate components similar in properties, the isotope dilution method is also used. Radiometric titration and radioactive indicators are also used. An original version of the combination of radioisotope and chromatographic methods is the study of diffusion-sedimentary chromatograms in thin layer of gelatin gel using radioactive tracers.

4.5 Methods based on the use of a magnetic field

The methods of NMR and PMR spectroscopy, as well as mass spectrometry, are characterized by high specificity and sensitivity and are used to analyze multicomponent mixtures, including dosage forms, without their preliminary separation.

NMR spectroscopy is used to test the authenticity of medicinal substances, which can be confirmed either by the full set of spectral parameters characterizing the structure of a given compound, or by the most characteristic spectral signals. Authenticity can also be established using a standard sample by adding a certain amount of it to the analyzed solution. Full coincidence of the spectra of the analyte and its mixture with the standard sample indicates their identity.

Registration of NMR spectra is performed on spectrometers with operating frequencies of 60 MHz or more, using such basic spectral characteristics as chemical shift, resonance signal multiplicity, spin-spin interaction constant, and resonance signal area. The most extensive information on the molecular structure of the analyte is provided by 13C and 1H NMR spectra.

Reliable identification of preparations of gestagenic and estrogenic hormones, as well as their synthetic analogues: progesterone, pregnin, ethinylestradiol, methylestradiol, estradiol dipropionate, etc. - can be carried out by 1H NMR spectroscopy in deuterated chloroform on a UN-90 spectrometer with an operating frequency of 90 MHz (internal standard - tetramethylsilane).

Systematic studies have made it possible to establish the possibility of using 13C NMR spectroscopy for the identification of medicinal substances of 10-acyl derivatives of phenothiazine (chloracizine, fluorocyzine, ethmosine, etacizine), 1,4-benzodiazepine (chlorine, bromo, and nitro derivatives), etc. Using 1H NMR spectroscopy and 13 C, identification, quantitative assessment of the main components and impurities in preparations and standard samples of natural and semi-synthetic antibiotics of aminoglycosides, penicillins, cephalosporins, macrolides, etc. was carried out. This method was used to identify a number of vitamins under unified conditions: lipoic and ascorbic acids, lipamide, choline and methylmethioninesulfonium chlorides, retinol palmitate, calcium pantothenate, ergocalciferol. The method of 1H NMR spectroscopy made it possible to reliably identify such natural compounds with complex chemical structures as cardiac glycosides (digoxin, digitoxin, celanide, dezlanoside, neriolin, cymarin, etc.). A computer was used to speed up the processing of spectral information. A number of identification methods are included in the FS and VFS (V.S. Kartashov).

Quantification of the drug substance can also be performed using NMR spectra. The relative error of quantitative determinations by the NMR method depends on the accuracy of measurements of the areas of resonant signals and is ± 2--5%. When determining the relative content of a substance or its impurity, the areas of the resonance signals of the test substance and the standard sample are measured. The amount of the test substance is then calculated. To determine the absolute content of a drug substance or impurity, the analyzed samples are prepared quantitatively and an accurately weighed mass of the internal standard is added to the sample. After that, the spectrum is recorded, the areas of the signals of the analyte (impurity) and the internal standard are measured, and then the absolute content is calculated.

The development of pulsed Fourier spectroscopy techniques and the use of computers made it possible to sharply increase the sensitivity of the 13C NMR method and extend it to the quantitative analysis of multicomponent mixtures of bioorganic compounds, including medicinal substances, without their preliminary separation.

The spectroscopic parameters of the NMR spectra provide a whole range of diverse and highly selective information that can be used in pharmaceutical analysis. The conditions for recording spectra should be strictly observed, since the values ​​of chemical shifts and other parameters are affected by the type of solvent, temperature, pH of the solution, and concentration of the substance.

If a complete interpretation of the PMR spectra is difficult, then only characteristic signals are isolated, by which the test substance is identified. NMR spectroscopy has been used to test the authenticity of many medicinal substances, including barbiturates, hormonal agents, antibiotics, etc.

Since the method provides information about the presence or absence of impurities in the base substance, it is important practical value has NMR spectroscopy for testing medicinal substances for purity. Differences in the values ​​of certain constants allow us to conclude that there are impurities of the degradation products of the medicinal substance. The sensitivity of the method to impurities varies widely and depends on the spectrum of the main substance, the presence of various groups containing protons in the molecules, and the solubility in the corresponding solvents. The minimum impurity content that can be set is usually 1--2%. Especially valuable is the possibility of detecting isomer impurities, the presence of which cannot be confirmed by other methods. For example, an admixture of salicylic acid in acetylsalicylic acid, morphine in codeine, etc. was found.

Quantitative analysis based on the use of NMR spectroscopy has advantages over other methods in that when analyzing multicomponent mixtures, there is no need to isolate individual components for instrument calibration. Therefore, the method is widely applicable for the quantitative analysis of both individual medicinal substances and solutions, tablets, capsules, suspensions and other dosage forms containing one or more ingredients. The standard deviation does not exceed ±2.76%. Methods for analyzing tablets of furosemide, meprobamate, quinidine, prednisolone, etc. are described.

The range of application of mass spectrometry in the analysis of medicinal substances for identification and quantitative analysis is expanding. The method is based on the ionization of molecules of organic compounds. It is highly informative and extremely sensitive. Mass spectrometry is used to determine antibiotics, vitamins, purine bases, steroids, amino acids and other medicinal substances, as well as their metabolic products.

The use of lasers in analytical instruments significantly expands the practical application of UV and IR spectrophotometry, as well as fluorescence and mass spectroscopy, Raman spectroscopy, nephelometry, and other methods. Laser sources of excitation make it possible to increase the sensitivity of many methods of analysis and reduce the duration of their execution. Lasers are used in remote analysis as detectors in chromatography, bioanalytical chemistry, etc.

4.6 Electrochemical methods

This group of methods for qualitative and quantitative analysis is based on electrochemical phenomena occurring in the medium under study and associated with changes in the chemical structure, physical properties or concentration of substances.

Potentiometry is a method based on measuring the equilibrium potentials that arise at the boundary between the test solution and an electrode immersed in it. SP XI includes the method of potentiometric titration, which consists in establishing the equivalent volume of the titrant by measuring the EMF of the indicator electrode and the reference electrode immersed in the analyzed solution. The method of direct potentiometry is used to determine the pH (pH-metry) and establish the concentration of individual ions. Potentiometric titration differs from indicator titration in the ability to analyze strongly colored, colloidal and turbid solutions, as well as solutions containing oxidizing agents. In addition, it is possible to sequentially titrate several components in a mixture in aqueous and non-aqueous media. The potentiometric method is used for titration based on reactions of neutralization, precipitation, complex formation, oxidation - reduction. The reference electrode in all these methods is calomel, silver chloride or glass (the latter is not used in the analysis by the neutralization method). Indicator in acid-base titration is a glass electrode, in complexometric - mercury or ion-selective, in the deposition method - silver, in redox - platinum.

The measurement of the EMF that occurs during titration due to the potential difference between the indicator electrode and the reference electrode is carried out using high-resistance pH meters. The titrant is added from the buret in equal volumes, constantly stirring the liquid to be titrated. Near the equivalence point, the titrant is added in 0.1--0.05 ml. The EMF value at this point changes most strongly, since the absolute value of the ratio of the change in EMF to the increment in the volume of the added titrant will be maximum in this case. Titration results are presented either graphically by setting the equivalence point on the titration curve, or by calculation. Then the equivalent volume of the titrant is calculated using the formulas (see SP XI, issue 1, p. 121).

Amperometric titration with two indicator electrodes, or titration "until the current stops completely", is based on the use of a pair of identical inert electrodes (platinum, gold), which are under a small voltage. The method is most often used for nitrite and iodometric titration. The equivalence point is found by a sharp increase in the current passing through the cell (within 30 s) after the addition of the last portion of the reagent. This point can be established graphically by the dependence of the current strength on the volume of the added reagent, just as in potentiometric titration (SP XI, issue 1, p. 123). Methods for biamperometric titration of medicinal substances have also been developed using nitritemetry, precipitation and oxidation-reduction methods.

Particularly promising is ionometry, which uses the relationship between the EMF of a galvanic network with an ion-selective electrode and the concentration of the analyzed ion in the electrode cell of the circuit. The determination of inorganic and organic (nitrogen-containing) medicinal substances using ion-selective electrodes differs from other methods in high sensitivity, rapidity, good reproducibility of results, simple equipment, available reagents, suitability for automated control and study of the mechanism of drug action. As an example, methods for the ionometric determination of potassium, sodium, halides and calcium-containing medicinal substances in tablets and in saline blood-substituting liquids can be cited. With the help of domestic pH meters (pH-121, pH-673), an I-115 ionometer and potassium selective electrodes, potassium salts of various acids (orotic, aspartic, etc.) are determined.

Polarography is an analysis method based on measuring the strength of the current that occurs on the microelectrode during electroreduction or electrooxidation of the analyte in solution. Electrolysis is carried out in a polarographic cell, which consists of an electrolyzer (vessel) and two electrodes. One is a dropping mercury microelectrode, and the other is a macroelectrode, which is either a mercury layer on the cell or an external saturated calomel electrode. Polarographic analysis can be performed in an aqueous medium, in mixed solvents (water - ethanol, water - acetone), in non-aqueous media (ethanol, acetone, dimethylformamide, etc.). Under identical measurement conditions, the half-wave potential is used to identify the substance. Quantification is based on the measurement of the limiting diffuse current of the tested medicinal substance (wave height). To determine the content, the method of calibration curves, the method of standard solutions and the method of additives are used (GF XI, issue 1, p. 154). Polarography is widely used in the analysis inorganic substances, as well as alkaloids, vitamins, hormones, antibiotics, cardiac glycosides. Due to the high sensitivity, modern methods are very promising: differential pulse polarography, oscillographic polarography, etc.

The possibilities of electrochemical methods in pharmaceutical analysis are far from being exhausted. New variants of potentiometry are being developed: inversion currentless chronopotentiometry, direct potentiometry using a gaseous ammonium-selective electrode, etc. Research is being expanded in the field of application in pharmaceutical analysis of such methods as conductometry, based on the study of the electrical conductivity of solutions of analytes; coulometry, which consists in measuring the amount of electricity spent on the electrochemical reduction or oxidation of the ions being determined.

Coulometry has a number of advantages over other physicochemical and chemical methods. Since this method is based on measuring the amount of electricity, it makes it possible to directly determine the mass of a substance, and not any property proportional to the concentration. That is why coulometry eliminates the need to use not only standard, but also titrated solutions. As for coulometric titration, it expands the field of titrimetry through the use of various unstable electrogenerated titrants. The same electrochemical cell can be used to carry out titration using different types of chemical reactions. Thus, the neutralization method can determine acids and bases even in millimolar solutions with an error of no more than 0.5%.

The coulometric method is used in the determination of small amounts of anabolic steroids, local anesthetics and other medicinal substances. The determination is not interfered with by tablet excipients. The methods are characterized by simplicity, rapidity, speed and sensitivity.

The method of dielectric measurements in the range of electromagnetic waves is widely used for express analysis in chemical technology, food industry and other areas. One of the promising areas is dielcometric control of enzyme and other biological products. It allows for a quick, accurate, reagent-free assessment of parameters such as moisture, degree of homogeneity and purity of the drug. The dielcometric control is multi-parameter, the test solutions can be opaque, and the measurements can be performed in a non-contact way with the results recorded on a computer.

4.7 Separation methods

Of the physicochemical separation methods in pharmaceutical analysis, chromatography, electrophoresis and extraction are mainly used.

Chromatographic methods for the separation of substances are based on their distribution between two phases: mobile and stationary. The mobile phase can be a liquid or a gas, while the stationary phase can be a solid or a liquid adsorbed on a solid carrier. The relative speed of movement of particles along the separation path depends on their interaction with the stationary phase. This leads to the fact that each of the substances passes a certain path length on the carrier. The ratio of the rate of movement of the substance to the rate of movement of the solvent denote This value is a constant of the substance for given separation conditions and is used for identification.

Chromatography makes it possible to most effectively carry out the selective distribution of the components of the analyzed sample. This is of essential importance for pharmaceutical analysis, in which the objects of study are usually mixtures of several substances.

According to the mechanism of the separation process, chromatographic methods are classified into ion-exchange, adsorption, sedimentary, distribution, redox chromatography. According to the form of the process, column, capillary and planar chromatography can be distinguished. The latter can be performed on paper and in a thin (fixed or unfixed) sorbent layer. Chromatographic methods are also classified according to the state of aggregation of the analyte. These include various methods of gas and liquid chromatography.

Adsorption chromatography is based on the selective adsorption of individual components from a solution of a mixture of substances. The stationary phase is adsorbents such as aluminum oxide, activated carbon, etc.

Ion exchange chromatography uses ion exchange processes occurring between the adsorbent and electrolyte ions in the analyzed solution. Cation-exchange or anion-exchange resins serve as the stationary phase; the ions contained in them are capable of being exchanged for like-charged counterions.

Sedimentary chromatography is based on the difference in the solubility of substances formed during the interaction of the components of the mixture being separated with a precipitant.

Partition chromatography consists in the distribution of the components of the mixture between two immiscible liquid phases (mobile and stationary). The stationary phase is a solvent-impregnated carrier, and the mobile phase is an organic solvent that is practically immiscible with the first solvent. When the process is performed in the column, the mixture is separated into zones containing one component each. Partition chromatography can also be performed in a thin layer of sorbent (thin layer chromatography) and on chromatographic paper (paper chromatography).

Earlier than other separation methods in pharmaceutical analysis, ion-exchange chromatography began to be used for the quantitative determination of drugs: salts of sulfuric, citric and other acids. In this case, ion-exchange chromatography is combined with acid-base titration. The improvement of the method made it possible, using reverse phase ion pair chromatography, to separate some hydrophilic organic compounds. It is possible to combine complexometry with the use of cation exchangers in Zn 2+ -form for the analysis of amine derivatives in mixtures and alkaloids in extracts and tinctures. Thus, the combination of ion-exchange chromatography with other methods expands the scope of its application.

In 1975 proposed new version chromatography, used to determine ions and called ion chromatography. Columns of 25 x 0.4 cm in size are used to perform the analysis. Two-column and single-column ion chromatography has been developed. The first one is based on ion-exchange separation of ions on one column followed by a decrease in the background signal of the eluent on the second column and conductometric detection, and the second one (without suppression of the background signal of the eluent) is combined with photometric, atomic absorption, and other methods for detecting the ions to be determined.

Despite the limited number of works on the use of ion chromatography in pharmaceutical analysis, this method is obviously promising for the simultaneous determination of the anionic composition of multicomponent dosage forms and saline solutions for injection (containing sulfate, chloride, carbonate, phosphate ions), for the quantitative determination of heteroelements in organic medicinal substances (containing halogens, sulfur, phosphorus, arsenic), to determine the level of contamination of water used in the pharmaceutical industry with various anions, to determine some organic ions in dosage forms.

The advantages of ion chromatography are the high selectivity of ion determination, the possibility of simultaneous determination of organic and inorganic ions, a low limit detected (up to 10 -3 and even 10 min, separation of up to 10 ions is possible), simplicity of hardware, the possibility of combining with other analytical methods and expanding the scope of chromatography in relation to objects similar in chemical structure and difficult to separate by TLC, GLC, HPLC.

The most widely used in pharmaceutical analysis are paper chromatography and chromatography in a thin layer of a sorbent.

In paper chromatography, the stationary phase is the surface of a special chromatographic paper. The distribution of substances occurs between the water on the surface of the paper and the mobile phase. The latter is a system that includes several solvents.

In pharmaceutical analysis, when performing tests by paper chromatography, they are guided by the instructions of the Global Fund XI, vol. 1 (p. 98) and private pharmacopoeial articles on the corresponding medicinal substances (dosage forms). In identity tests, the test substance and the corresponding reference standard are chromatographed on the same sheet of chromatographic paper at the same time. If both substances are identical, then the corresponding spots on the chromatograms have the same appearance and equal values ​​of R f . If a mixture of test substance and standard sample is chromatographed, then only one spot should appear on the chromatogram if they are identical. To eliminate the influence of chromatographic conditions on the obtained values ​​of R f , you can use a more objective value of R S , which is the ratio of the R f values ​​of the test and standard samples.

When testing for purity, the presence of impurities is judged by the size and color intensity of the spots on the chromatogram. The impurity and the main substance must have different Rf values. For semi-quantitative determination of the impurity content on one sheet of paper, a chromatogram of the test substance taken in a certain amount and several chromatograms of a standard sample taken in exactly measured quantities are simultaneously obtained under the same conditions. Then, the chromatograms of the tested and standard samples are compared with each other. The conclusion about the amount of impurities is made by the size of the spots and their intensity.

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Introduction

1.2 Errors in Pharmaceutical Analysis

1.3 General principles authenticity testing of medicinal substances

1.4 Sources and causes of poor quality of medicinal substances

1.5 General requirements for purity testing

1.6 Methods of pharmaceutical analysis and their classification

Chapter 2. Physical Methods of Analysis

2.1 Verification of physical properties or measurement of physical constants of drug substances

2.2 Setting the pH of the medium

2.3 Determination of clarity and turbidity of solutions

2.4 Estimation of chemical constants

Chapter 3. Chemical Methods of Analysis

3.1 Features of chemical methods of analysis

3.2 Gravimetric (weight) method

3.3 Titrimetric (volumetric) methods

3.4 Gasometric analysis

3.5 Quantitative elemental analysis

Chapter 4. Physical and chemical methods of analysis

4.1 Features of physicochemical methods of analysis

4.2 Optical methods

4.3 Absorption methods

4.4 Methods based on emission of radiation

4.5 Methods based on the use of a magnetic field

4.6 Electrochemical methods

4.7 Separation methods

4.8 Thermal methods of analysis

Chapter 5

5.1 Biological quality control of medicines

5.2 Microbiological control of medicinal products

List of used literature

Introduction

Pharmaceutical analysis is the science of chemical characterization and measurement of biologically active substances at all stages of production: from the control of raw materials to the assessment of the quality of the resulting medicinal substance, the study of its stability, the establishment of expiration dates and the standardization of the finished dosage form. Pharmaceutical analysis has its own specific features that distinguish it from other types of analysis. These features lie in the fact that substances of various chemical nature are subjected to analysis: inorganic, organoelement, radioactive, organic compounds from simple aliphatic to complex natural biologically active substances. The range of concentrations of analytes is extremely wide. The objects of pharmaceutical analysis are not only individual medicinal substances, but also mixtures containing a different number of components. The number of medicines is increasing every year. This necessitates the development of new methods of analysis.

Methods of pharmaceutical analysis need to be systematically improved due to the continuous increase in the requirements for the quality of drugs, and the requirements for both the degree of purity of medicinal substances and the quantitative content are growing. Therefore, it is necessary to widely use not only chemical, but also more sensitive physical and chemical methods for assessing the quality of drugs.

The requirements for pharmaceutical analysis are high. It should be sufficiently specific and sensitive, accurate in relation to the standards stipulated by GF XI, VFS, FS and other scientific and technical documentation, carried out in short periods of time using minimal quantities of tested drugs and reagents.

Pharmaceutical analysis, depending on the tasks, includes various forms of drug quality control: pharmacopoeial analysis, step-by-step control of the production of medicines, analysis of individual dosage forms, express analysis in a pharmacy, and biopharmaceutical analysis.

Pharmacopoeial analysis is an integral part of pharmaceutical analysis. It is a set of methods for the study of drugs and dosage forms set forth in the State Pharmacopoeia or other regulatory and technical documentation (VFS, FS). Based on the results obtained during the pharmacopoeial analysis, a conclusion is made on the compliance of the medicinal product with the requirements of the Global Fund or other regulatory and technical documentation. In case of deviation from these requirements, the drug is not allowed to be used.

The conclusion about the quality of the medicinal product can only be made on the basis of the analysis of the sample (sample). The procedure for its selection is indicated either in a private article or in a general article of the Global Fund XI (issue 2). Sampling is carried out only from undamaged sealed and packed in accordance with the requirements of the NTD packaging units. At the same time, the requirements for precautionary measures for working with poisonous and narcotic drugs, as well as for toxicity, flammability, explosiveness, hygroscopicity and other properties of drugs, must be strictly observed. To test for compliance with the requirements of the NTD, multi-stage sampling is carried out. The number of steps is determined by the type of packaging. At the last stage (after control by appearance), a sample is taken in the amount necessary for four complete physical and chemical analyzes (if the sample is taken for controlling organizations, then for six such analyzes).

From the "angro" packaging, point samples are taken, taken in equal quantities from the top, middle and bottom layers of each packaging unit. After establishing homogeneity, all these samples are mixed. Loose and viscous drugs are taken with a sampler made of an inert material. Liquid medicinal products are thoroughly mixed before sampling. If this is difficult to do, then point samples are taken from different layers. The selection of samples of finished medicinal products is carried out in accordance with the requirements of private articles or control instructions approved by the Ministry of Health of the Russian Federation.

Performing a pharmacopoeial analysis allows you to establish the authenticity of the drug, its purity, determine the quantitative content of pharmacologically active substance or ingredients that make up the dosage form. While each of these stages has a specific purpose, they cannot be viewed in isolation. They are interrelated and complement each other. For example, melting point, solubility, pH of an aqueous solution, etc. are criteria for both authenticity and purity of a medicinal substance.

Chapter 1. Basic Principles of Pharmaceutical Analysis

1.1 Pharmaceutical analysis criteria

At various stages of pharmaceutical analysis, depending on the tasks set, such criteria as selectivity, sensitivity, accuracy, time spent on the analysis, and the amount of the analyzed drug (dosage form) are important.

The selectivity of the method is very important when analyzing mixtures of substances, since it makes it possible to obtain the true values ​​of each of the components. Only selective methods of analysis make it possible to determine the content of the main component in the presence of decomposition products and other impurities.

Requirements for the accuracy and sensitivity of pharmaceutical analysis depend on the object and purpose of the study. When testing the degree of purity of the drug, methods are used that are highly sensitive, allowing you to set the minimum content of impurities.

When performing step-by-step production control, as well as when conducting express analysis in a pharmacy, an important role is played by the time factor spent on the analysis. For this, methods are chosen that allow the analysis to be carried out in the shortest time intervals and at the same time with sufficient accuracy.

In the quantitative determination of a medicinal substance, a method is used that is distinguished by selectivity and high accuracy. The sensitivity of the method is neglected, given the possibility of performing an analysis with a large sample of the drug.

A measure of the sensitivity of a reaction is the limit of detection. It means the lowest content at which the presence of the determined component can be detected by this method with a given confidence level. The term "limit of detection" was introduced instead of such a concept as "discovered minimum", it is also used instead of the term "sensitivity". qualitative reactions factors such as volumes of solutions of reacting components, concentrations of reagents, pH of the medium, temperature, and duration of the experiment influence. This should be taken into account when developing methods for qualitative pharmaceutical analysis. To establish the sensitivity of reactions, the absorption index (specific or molar) is increasingly used, which is established by the spectrophotometric method. In chemical analysis, the sensitivity is set by the value of the limit of detection of a given reaction. Physicochemical methods of analysis are distinguished by high sensitivity. The most highly sensitive are radiochemical and mass spectral methods, which make it possible to determine 10 -8 -10 -9% of the analyte, polarographic and fluorimetric 10 -6 -10 -9%; sensitivity of spectrophotometric methods Yu -3 -10 -6%, potentiometric methods 10 -2%.

The term "analysis accuracy" simultaneously includes two concepts: reproducibility and correctness of the obtained results. Reproducibility characterizes the scatter of the results of an analysis compared to the mean. Correctness reflects the difference between the actual and found content of the substance. The accuracy of the analysis for each method is different and depends on many factors: the calibration of measuring instruments, the accuracy of weighing or measuring, the experience of the analyst, etc. The accuracy of the analysis result cannot be higher than the accuracy of the least accurate measurement.