كمص 428

يحتوي المقرر على دراسة المعالجة الكيماوية للأمراض التي تسببها الطفيليات والخلايا السرطانية وطرق التحضير والتسمية والعلاقة بين التركيب البنائي والفاعلية الحيوية لهذه المركبات العلاجية. ويشتمل الجزء العملي على طرق التشييد والتحليل الدوائي و التنقية والتأكد من التركيب البنائى باستخدام طرق دساتير الأدوية العالمية والطرق   الطيفية التطبيقية الأخرى.

 

References

 

1- Williams, D.A. and Lemeke, T.L., Foye’s Principle of Medicinal Chemistry, Lippincott Williams & Wilkins, Philadelphia, PA., Latest edition.

 2- Gareth Thomas. Medicinal Chemistry, An Introduction, John Wiley & Sons, Ltd, Latest edition.

 Ingredients of the course:-

 Part I:

-     

 Practical Lab I : Assay of Aspirin 

-     

 Practical Lab II : Assay of Sandoz ampule + Vitc tablet 

-     

Practical Lab III : Assay of Eye Drop Sample 

-     

Practical Lab  IV: Assay of Indomethacin 

-     

Practical Lab V: Assay of Rehydrate Solution 

 Part II:

-     

Practical Lab I :Assay of Eye lotion Mixture

-     

Practical Lab II :Assay of Scalp Mixture

-     

Practical Lab III: Assay For Furosemide (Lazix ®)

-     

Practical Lab IV: Assay of Paracetamol

-     

Practical Lab V: Assay of Ear drops

 INTRODUCTION:

In this course you will learn about drug analysis which is a very important step in drug quality control to determine the concentration of active constituents used in different dosage forms that are administered to humane body.

In each lab. we will determine the percentage of content of active constituent  in a given dosage form by different analytical methods in the pharmacopeia.

Two chemical methods will be used in this course:

1)   

 Titerimetric methods.

2)   

 Spectrophotometric methods.

1)Titerimetric methods:

In this method the tested substance (analyte or sample) react with a reagent added as a solution of known concentration ( standard or titrant) and when the reaction is complete,  the end point will be observed.

Classification of titration according to the method used:

a)    

 Direct titration:

The sample react with the standard until the end point appears .

b)   

 Indirect titration:

Addition of a reagent to the sample leading to formation of intermediate that have an equivalent amount to the sample followed by titration of this intermediate with a suitable titrant .

c)    

 Back titration:

By first adding to the sample a measured volume of standard solution more than sufficient to bring a known chemical reaction the determine the excess by another titrant.

Classification of titration according to the nature of the chemical reaction:

1)   

 Acid-base titration

2)   

 Redox titration

3)   

 Preceptation titration

4)   

 Complex formation titration

 LAB 1: Assay of Aspirin Tablet

                                Aspirin is an acid and the active ingredient of it is acetyl salicylic acid.

Uses:

 I-Direct acid-base titration:

Direct titration is a way to determine how much acid is in a solution by adding just enough base of a known concentration to neutralize the acid. In a neutralization, the number of moles of acid, H+, are combined with an equal number of moles of base, OH-. In the titration you will be performing, you will dispense base into a known amount of acid solution to find the unknown concentration.

Procedure:

-        

 In a conical flask dissolve a quantity of powdered aspirin equivalent to 0.2 gm in 10 ml ethanol.

-        

 Add 3 drops of phenol red indicator .

-        

 Titrate with N/10 NaOH.

 Principle & calculations: 

 II-Indirect acid-base titration:

Aspirin is reacted with an excess of Alkali which produces a water soluble salt of aspirin and the excess alkali  may then be determined by titration with an acid 

Procedure:

-        

 In a conical flask add a quantity equivalent to 0.3 gm aspirin

-        

  add 20 ml N/2 NaOH

-        

 Boil for 5min., cool and titrate with N/2 H2SO4 using phenol red as an indicator.

Principle & calculation:LAB 2:

Assay of Calcium Sandoz ampule & vitamine C Tablet

Each ampoule contains

Rx

          Ascorbic acid                 1 g 

Calcium Gluconate        1 g 

A. Assay of Vitamin C (Ascorbic acid) content in the Ampoule: 

 

It is a water soluble vitamin with antioxidant activity.

Uses: 

I. By lodimetry Method:

This method determines the vitamin C concentration in a solution by a redox titration using iodine. As the iodine is added during the titration, the ascorbic acid is oxidised to dehydroascorbic acid, while the iodine is reduced to iodide ions.

ascorbic acid + I₂ --> 2 I^- + dehydroascorbic acid

Due to this reaction, the iodine formed is immediately reduced to iodide as long as there is any ascorbic acid present. Once all the ascorbic acid has been oxidised, the excess iodine is free to react with the starch indicator, forming the blue-black starch-iodine complex. This is the endpoint of the titration.

Principle:

 

Procedure:

- Pipette 20 ml of vitamin C sample to a glass Stoppard conical flask (G.S.C.F.)

- dilute with 20 ml distilled water

- add 5 ml dil. H₂S0₄

- Titrate with N/20 I₂ using starch as indicator (add starch from the beginning of the titration)

Calculation:

B. Assay of calcium gluconate content of the ampule

II. By Compleximetry Method (EDTA Method):

The technique involves titrating metal ions with a complexing agent or chelating agent (Ligand) and is commonly referred to as complexometric titration. In this method, a simple ion is transformed into a complex ion and the equivalence point is determined by using metal indicators 

Principle:

Procedure:

-Transfer 10 ml of Ca gluconate To a conical flask

-dilute with 20 ml distilled water

- add 5 ml ammonia buffer

-Titrate with M/l00 EDTA using Eriochrorne Black T [EBT] as indicator. 

Calculation:

 C. Assay of Ascorbic Acid tablet:

Each tablet contains 500 mg of Ascorbic acid:

I. By Potassium lodate Method (Andrew’s reaction):

Principle:

6C₆H₈O₆ + 2KIO₃                 6C₆H₆O₆ + 2KI + 6H₂O

5KI + KIO₃ + 6HCL                 3I₂ + 6KCL + 3H₂O

(Brown)

KIO₃ + 2I₂ + 6HCL                 5ICL + KCL + 3H₂O  

  (Yellow)

                             

 6C₆H₈O₆ + 3KIO₃ + 6HCL                6C₆H₆O₆ + 3ICL + 3KCL + 9H₂O

Procedure:

-Weight and powder 10 tablets.

-Transfer a quantity of the powdered tablet equivalent to 0.15 gm ascorbic acid to G.S.C.F.

-Add 20 ml distilled water, 20 ml conc. HCI and 5 ml CHCI₃ (as indicator).

-Titrate with M/20 KIO3 till the violet color disappears from the chloroform layer.

Calculation:Lab 3: Assay of Eye Drop  Sample

Rx

          Zinc Sulphate

Boric acid

Phenazone

I. Assay of Zinc sulphate content  by compleximetry method:

- Principle:

- Procedure:

Transfer 10 ml of the sample to a conical flask, add 20 ml distilled water and 5 ml ammonia buffer. Titrate with M/100 EDTA using E.B.T as indicator.

- Calculation:

II. Assay of Phenazone content by Iodometry method:

- Principle:

 - Procedure:

Transfers 10 ml of the sample to a G.S.C.F. add 10 ml of 10% sodium acetate solution and 25 ml of N/20 I2 solution. Allow to stand for 15mim. with occasional shaking. Add 5ml chloroform, shake gently to dissolve the precipitate and then titrate with N/20 Na₂S₂O₃ using starch as indicator. A blank experiment must be carried out.

- Calculation:

 III Assay of Boric acid content by acid-base titration:

- Principle:

- Procedure:

Transfer 10 ml of the sample to a conical flask. Dilute with 20 ml distilled water and then add 20 ml neutral glycerol and titrate with N/10 NaoH using ph.ph. as indicator (8-10 drops).

- Calculation.

lab 4 Assay of Rehydrate Solution

Rx  

            Sodium hydrogen Carbonate

Sodium Chloride

Potassium Chloride

Glucose

Dist. H2O

I. Assay for NaHCO3:

- Principle:

 - Procedure:

Transfer 10 ml of the sample into a conical flask, dilute with 20 ml distilled water and titrate with N/10 H₂S0₄ using methyl orange as an indicator (one drop).

- Calculation:

 II. Assay for Total Chloride:

A]. By (Mohr’s Method):

- Principle:

 - Procedure:

Transfer 10 ml of the sample to a G.S.C.F, add the same volume of N/10 H₂SO₄ consumed in the first titration. Boil for 1min. to get rid of CO₂.

Cool, dilute with 20 ml distilled water and then titrate with N/10 AgNO₃ using K₂Cr₂O₄ as indicator (0.5 ml).

- Calculation:

 B]. By (Volhard’s Method):

- Principle:

 - Procedure:

Transfer 10 ml of the sample into a beaker. Add 10 ml dil. HNO₃ followed by 20 ml N/10 AgNO₃. mix well and filter into a conical flask. Wash the beaker and the filter paper three times each with 10 ml distilled water. Titrate the combined filtrate and washing with N/10 NH4SCN using ferric alum as indicator (1-2 ml).

- Calculation:

II Assay for Glucose:

- Principle:

- Procedure:

Transfer 10 ml of the sample to G.S.C.F., add 25 ml of N/l0 I2 solution followed by drop-wise addition of 10% NaOH solution until a yellow color is obtained (about 2-2.5 ml). Allow standing for 10 min then adding 10 ml dil. H₂SO₄ and titrate the librated Iodine with N/10 Na2S2O3 using starch mucilage as indicator (1 ml added near the end point). A blank experiment must be carried out.

- Calculation:

LAB 5

ASSAY OF SCALP MIXTURE

R_x 

        Salicylic acid

       Chloral Hydrate

       Resorcinol

1) Assay for Salicylic acid:

-Principle:

 -Procedure:

Transfer 10ml of the sample to a conical flask, dilute with 20ml of distilled water and titrate with N/l0 NaOH using phenol red as an indicator.

-Calculation:2) Assay for chloral hydrate:

-Principle:

-Procedure:

To the above neutral solution, add 25 ml N/1 NaOH, allow standing for 10 minutes and titrating with N/1 H₂ SO₄ acid until the red colour changes to yellow.

-Calculation:

 3) Assay for Resorcinol + Salicylic Acids:

-Principle:

 -Procedure:

Transfer 10 ml the sample to a measuring flask 100 ml, complete to the mark with distilled water. Transfer 10 ml of this dilute solution to a glass Stoppard conical flask, add 25 ml of N/10 Br₂ and 5ml of conc. HCL and allow standing for 30 minutes. Add 10 ml KI solution and 5 ml CHCI₃ Shake gently and titrate with N/l0 Na₂S₂O₃ using starch as an indicator.

-Calculation:

 lab 6

Assay of eye Lotion

R_x     

           NaHCO₃

Boric Acid

NaC1

H₂O

 

1) ASSAY FOR NaHCO₃

- 

Principle:

 -  Procedure:

For NaHCO3 :Transfer 10 ml of the sample to a conical flask, dilute with 20 ml of distilled water and titrate with N/10 H₂SO₄ acid using methyl orange as an indicator (1-2 drops).

For Boric acid: Boil for 4 min. to drive off CO₂ and then cool. Add 20 ml of neutral glycerol and titrate with N/l0 NaOH using ph.ph as indicator (10 drops).

-Calculation:

2) Assay for Boric acid (H₃Bo₃):

- 

Principle:

-  Procedure: see the first procedure.

-  -Calculation:

 

 

3) Assay for NaCL: (Mohor’s Method)

- Principle:

-  Procedure:

Transfer 10 ml of the sample into a glass Stoppard conical flask, then add the same volume of N/l0 H₂SO₄ acid used in the first titration and boil for 3 min to drive off CO₂ Allow to cool, dilute with 20 ml of distilled water and titrate with N/l0 AgNO₃ using K₂CrO₄ as an indicator (0.5-0.7 ml).

-Calculation: