METHODICAL INSTRUCTION FOR STUDENTS OF THE 3rd COURSE
Pharmaceutical Faculty
LESSON № 17 (PRACTICAL – 6 HOURS)
Theme: Pharmaceutical analysis of pyrazole (pyrazolone-3, pyrazolidine-3,5-dione) derivatives as drug substances: synthesis, properties, analysis, storage, action and use.
Aim: to acquire theoretical knowledge and practical skills for quality analysis, tests and quantitative definition of five-membered heterocycles.
Professional orientation of students:
The five-membered heterocycles with two heteroatoms of Nitrogen are:
Pyrazole Imidazole
In the medicinal practice use such derivatives of pyrazole:
pyrazolone-3 derivatives pyrazolidine-3,5-dione derivatives
They are popular an anti-inflammatory; analgesic and antipyretic drugs. The most important derivatives of pyrazolone-3 are phenazone, dipyrone, propyphenazone; pyrazolidine-3,5-dione derivatives – phenylbutazone, tribuzone.
Considering the theoretical material, concerning methods of synthesis, physical and chemical properties, techniques of identification, tests and quantitative definition of drug substances, their storage conditions and application in the medical practice and pharmaceutical analysis, students acquire knowledge which are necessary in future for professional work.
Performing practical work, students get new practical skills and improve earlier ones from the quality control of drugs and pharmaceuticals.
Performing practical work, students get new practical skills and improve earlier ones from the quality control of drugs and pharmaceuticals.
Methodology of Practical Class
Phenazone
Phenazonum
C11H12N2O
188.2
DEFINITION
1,5-Dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one.
Content
99.0 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder or colourless crystals.
Solubility
Very soluble in water, in ethanol (96 per cent) and in methylene chloride.
IDENTIFICATION
C. (BP, SPU, suppl. 2). Reaction with sodium nitrite solution
To 1 ml of solution S (see Tests) add 4 ml of water R and 0.25 ml of dilute sulphuric acid R. Add 1 ml of sodium nitrite solution R. A green colour develops.
green colour
D. (BP, SPU, suppl. 2). Reaction with ferric chloride solution
To 1 ml of solution S add 4 ml of water R and 0.5 ml of ferric chloride solution R2. A red colour develops which is discharged on the addition of dilute sulphuric acid R.
red colour
TESTS
Solution S
Dissolve
ASSAY
(BP, SPU, suppl. 2). Iodometry, back titration
Dissolve
Carry out a blank titration.
1 ml of
1 mol 2 equivalents
HI + CH3COONa → NaI + CH3COOH
I2 + 2Na2S2O3 → 2NaI + Na2S4O6
Еm(C11H12N2O) = М.m/2
STORAGE
Protected from light.
Action and use
Analgesic; used to test hepatic drug-metabolizing activity.
Ph Eur
Individual Students Program
1. Latin names and synonyms, structural formulas and chemical names of Phenazone, Dipyrone (Metamizole Sodium), Propyphenazone, Phenylbutazone, Tribuzone.
2. Synthesis of afore-mentioned preparations.
3. Physical properties of investigated medical products.
4. Identification of Phenazone, Dipyrone (Metamizole Sodium), Phenylbutazone, Propyphenazone, Tribuzone.
5. Tests of above-mentioned substances.
6. The pharmacopoeial and other methods of quantitative definition of drug substances.
7. Storage conditions of above-mentioned drugs, according to their physical and chemical properties.
8. Application of drugs in the medical practice and pharmaceutical analysis.
Seminar discussion of theoretical issues
1. What are latiames of Phenazone, Dipyrone (Metamizole Sodium), Phenylbutazone, Propyphenazone, Tribuzone?
2. What are structures of Phenazone, Dipyrone (Metamizole Sodium), Phenylbutazone, Propyphenazone, Tribuzone?
3. What are methods of synthesis of drugs?
4. What reactions of identification of afore-mentioned preparations do you know?
5. What pharmacopoeial methods of assay of afore-mentioned preparations do you know?
6. What storage conditions of drugs do you know?
7. What are actions and use in the medical practice of given drugs?
Test evaluation and situational tasks
1. The initial substances for synthesis of Phenazone are:
A. Acetic acid and benzene
B. Benzene and water
C. Pyrazolone and benzene
D. Phenylhydrazine and acetacetic ester
E. Imidazole and ethanol
2. The other name of Dipyrone is:
A. Metamizole sodium
B. Phenazone
C. Phenylbutazone
D. Antipyrine
E. Budirol
3. The Pharmacopoeial method of assay for Phenylbutazone is:
A. Acidimetry, direct not water titration
B. Acidimetry, back titration in the presence of acetone
C. Alkalimetry, direct titration in the presence of acetone
D. Alkalimetry, direct not water titration
E. Acidimetry, direct titration in the presence of ether
4. For identification of Propyphenazone can be used silver nitrate solution. What colour of precipitate is formed?
A. White
B. Black
C. Yellow
D. Blue
E. Green
5. The appearance of Dipyrone is:
A. A white or almost white, crystalline powder
B. A white amorphus powder
C. A yellow crystalline powder
D. Light green, crystalline powder or bluish-green crystals
E. A clear, colourless liquid
6. This structure corresponds to the drug substance:
A. Dipyrone
B. Phenazone
C. Thiotriazoline
D. Polyvinylpyrrolidone
E. Nitrofurazone
7. This structure corresponds to the drug substance:
A. Dipyrone
B. Phenazone
C. Propyphenazone
D. Thiotriazoline
E. Polyvinylpyrrolidone
8. This structure corresponds to the drug substance:
A. Dipyrone
B. Phenylbutazone
C. Propiophenazone
D. Phenazone
E. Polyvinylpyrrolidone
9. This structure corresponds to the drug substance:
A. Dipyrone
B. Propiophenazone
C. Phenazone
D. Polyvinylpyrrolidone
E. Tribuzone
10. Phenazone can be used in the medical practice as:
A. Anthelmintic.
B. Antiseptic
C. Antithyroid
D. Analgesic
E. Sedative
- Calculate the loss in weight at drying of Dipyrone substance. For titration
0,1946 g of Dipyrone substance (M = 351,4 g/mol) was used 10,7 ml of0,05 M iodine (f = 1,0018). The percentage content of Dipyrone in a preparation is 100,2 %. - Calculate the percentage content of Phenazone in preparation. For this purpose was dissolve
0.1535 g of Phenazone substance (M = 188,23 g/mol) in some solvent, was added needing reagents, standard solution of iodine and was titrated with0.1 M sodium thisulphate (f = 1,0000). For titration of the exact shot of Phenazone substance was used 8,8 ml of0.1 M sodium thisulphate; for blank titration – 25,1 ml.
Initial level of knowledge and skills are checked by solving situational tasks for each topic, answers in test evaluations and constructive questions.
(the instructor has tests & situational tasks)
Student should know:
1. Latin names and synonyms, structure formulas and chemical names of Phenazone, Dipyrone (Metamizole Sodium), Phenylbutazone, Propyphenazone, Tribuzone.
2. Methods of synthesis of given drug substances.
3. Physical and chemical characteristics, methods of identification, establishment of high quality and quantitative definition of afore-mentioned drugs.
4. Storage conditions and application of drugs in medical practice and the pharmaceutical analysis.
Student should be able to:
1. To write reactions of identifications and assay of Phenazone, Dipyrone (Metamizole Sodium), Phenylbutazone, Propyphenazone, Tribuzone.
2. To calculate equivalent mass and mass fraction of active ingredients in investigated substances by different methods.
3. After analysis carrying out a conclusion about the hight quality of the drug substances.
Correct answers of test evaluations and situational tasks:
1. D;
1. 3,4 %; 2. 99,93 %.
References:
А – Basic:
1. The International Pharmacopoeia / World Health Organization. – 3rd Edition, Volume 5. Tests and general requirements for dosage forms; Quality specifications for pharmaceutical substances and dosage forms. –
2. European Pharmacopoeia /Directorate for the Quality of Medicines & HealthCare of the Council of
3. British Pharmacopoeia /published by The Stationery Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA). – Volumes I–IV. –
4. Sarker S.D. Chemistry for pharmacy students: general, organic, and natural product chemistry / S.D. Sarker, L. Nahar. –
5. Kar A. Pharmaceutical drug analysis. – Revised second edition. –
6. Lecture materials.
В – Additional:
1. David G. Watson. Pharmaceutical analysis. –
2. Cairns D. Essentials of Pharmaceutical Chemistry. – Third edition. –
Methodical instruction has been worked out by: associate professor L.M. Mosula
Methodical instruction was discussed and adopted at the Department sitting
on the 7-th of June 2012. Minute № 17
