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Impurities Source of impurities: During synthesis During manufacturing

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Presentation on theme: "Impurities Source of impurities: During synthesis During manufacturing"— Presentation transcript:


2 Impurities Source of impurities: During synthesis During manufacturing
During storage

3 Impurities Classification of chemicals : Commercial chemicals
Pure chemicals Analytical chemicals Pharmaceutical chemicals

4 official = obey the requirement
Pharmacopoeia A description of the article Tests for identity Physical constants Quantitative assay Limit test Storage conditions official = obey the requirement

5 Pharmacopoeia British pharmacopoeia (BP)
European pharmacopoeia (Eu.Ph) United state pharmacopoeia (USP)

6 Limit test They are quantitative or semi-quantitative test designed to identify or control small quantities of impurity ,these test should be specific and sensitive

7 Limit test Type: Comparison method Quantitative determination
Test in which there is no visible reaction

8 Limit test General principle
If the sample is lighter than the standard solution then it is within the pharmacopeial limit (accepted) If the sample is darker/heavier than the standard solution then it is above the pharmacopeial limit (rejected)

9 Limit test NESSLER cylinder ( appendix VII A127)
clear glasses with normal capacity 50ml, the overall height is about 15cm, the external height to the 50ml mark 11.0 to 12.4 cm ,the thickness of the wall 1.0 to 1.5 mm and the thickness of the base 1.0 to 3.0mm the external heights to the 50 mark of cylinders used to test must not differ by more than 1 mm

10 Limit test General precaution
The liquid used must be clean and filtered if necessary The Nessler cylinder must be made of colorless glass and of the same inner diameter Detecting opalescence or color development must be performed in daylight When comparing turbidity it should be done against black background When comparing color it should be done against white background

11 Limit test

12 Limit Test for Ammonium
Principle NH4+ + K2HgI NH2Hg2I3 0.3ml Nessler reagent 0.3ml Nessler reagent Add dis. water to 50 ml Add dist. water to 50 ml 10ml of standard NH4+ (1ppm) +5ml H2O 15ml sample solution

13 Limit Test for Chloride
Principle: AgCl Cl- + AgNO3 1ml AgNO3 1ml AgNO3 Dist. H2O to 50ml Dist. H2O to 50 ml 1ml HNO3 1ml HNO3 10ml St Cl- (5ppm) +5ml H2O 15ml sample

14 Limit Test of Sulphate Principle: SO4-2 + BaCl2 BaSO4
Complete volume with Dil.water to 50ml MIX by rotation & wait for 1 minute 1.5ml ethanolic SO4standard 15ml water Mix by rotation 1ml 25%BaCl2 Add 0.5ml acetic acid(5M 15ml sample 15ml Standard

15 Limit Test for Iron Principle: Fe+3 + NH4SCN Fe(SCN)3 Procedure:
5ml NH4SCN H2O to 50ml 5ml HNO3 10ml sample 5ml NH4SCN H2O to 50ml 5ml HNO3 10ml standard Why we use nitric acid?

16 10ml calcium stander (10ppm) 2ml calcium stander (100ppm)
Limit Test of Calcium Principle: Ca+2 + (NH4)2C2O CaC2O4 Procedure 0.2ml alcoholic calcium stander(100ppm) 1ml ammonium oxalate 1ml acetic acid to 50ml with dist water 1 MIN 10ml calcium stander (10ppm) 5 ml dist water 2ml calcium stander (100ppm) 20 ml dist water Pipette 15 ml

17 Aspirin Limit Test of Salicylic Acid
0.05 ml FeCl3 to 50ml H2O 15 ml iced H2O 0.1ml acetic acid 1ml salicylic acid 4ml ethanol 0.05 ml FeCl3 to 50ml H2O 15 ml iced H2O 0.1ml acetic acid 0.1gm sample 5ml ethanol

18 Limit Test of Heavy Metal
Principle: Pb+2 +NaS PbS 1.2ml thioacetamide mix 2ml acetate buffer 12ml sample 1.2ml thioacetamide mix 2ml acetate buffer 10ml standard Pb 2ml sample Sample preparation 2.5g aspirin dissolve in 30ml acetone then complete to 50 ml with H2O

19 Quantitative Limit Test
Determination of lead concentration in a sample of heavy metals Primary solution Auxiliary solution 5ml standard 4ml standard 3ml standard 2ml standard 5drops thioacetmide 5drops thioacetmide 1 ml NH4OH 1 ml NH4OH 3ml sample 1ml sample

20 Non Aqueous Acid-Base Titration
Main reasons for non aqueous titration : Solubility: many organic compound (acid or base) sparingly soluble in water but readily soluble in organic solvent Too weak acid or base : they didn’t give sharp end point in aqueous titration but can titrated accurately in suitable non aqueous solvent

21 Non Aqueous Acid-Base Titration
Inert neutral substance as :benzene , chloroform and hydrocarbon

22 Non Aqueous Acid-Base Titration
Protic solvent : Amphiprotic :it self dissociation (autoprotolysis) which process acidic and basic properties e,g:H2O,AcOH, ALCOHOL and liquid ammonia 2H2O H3O+ + OH- 2C2H5OH C2H5OH2+ +C2H5O- Protogenic: they have stronger acidic than basic properties (more acidic than water) E,g: CH3COOH & H2SO4 B + CH3COOH BH+ + CH3COO-

23 Non Aqueous Acid-Base Titration
Protic solvent : Protophilic : basic substance and react with acidic solute with the formation of solvated proton and conjugated base of acid (more basic than water) E,g :ether ,ketone & amine HB +S HS+ + B-

24 Non Aqueous Acid-Base Titration
Type of Titrant: Perchloric acid (HClO4)Used for titration in acetic acid media , it is commonly use for titration of weak media Alkali metal bases: alcoholic potassium hydroxide or alcoholic sodium hydroxide they used for titration of moderately weak acid Quaternary ammonium hydroxide: tetra butyl ammonium hydroxide the most widely used titrant for acid in non aqueous titration

25 Non Aqueous Acid-Base Titration
Advantage of These Titrant Excellent potentiometric curve using ordinary glass or calomel electrode The salt formed from this titration are soluble in the solvent commonly used

26 Titration of Adrenaline
Principle HClO4 + CH3COOH CH3COOH2+ + ClO4- + CH3COOH CH3COO + HClO ClO4-

27 Titration of Adrenaline
Volumetric: In dry conical flask weigh 0.2g adrenaline Add 25ml glacial acetic acid One drop crystal violet indicator Titrate against perchloric acid Poteatiometric In dry beaker 0.2g adrenaline 25ml glecial acetic acid Titate against perchloric acid End point when greenish blue appear Add 0.5ml until near the E.P add 0.1ml

28 Titration of Adrenaline
Calculation From the equivalent factor each ml of perchloric acid react with of C9H13NO3 F= (molecular weight of sample*molarities of standard) 1000 Theoretical (equivalent point) 1ml of 0.1M HClO g adrenaline X ml the weighted amount of sample X= equivalent point 0.2g adrenaline

29 Titration of Adrenaline
Calculation %of deviation= end point from the graph*100 equivalent point Limitation 101% -98,5%

30 Titration of Phenobarbitals

31 Titration of Phenobarbitals
Add 3 drop of to the alcohol then add sufficient amount of NaOH (0.02 or0.1N) TO produce PINK COLOR Volumetric titration In dry conical flask weight 0.5g Phenobarbital Add 40ml neutralized alcohol Add 20 ml water Titrate against 0.1N NaOH using as indicator Potentiometric titration In a dry beaker weight 0.5g Phenobarbital Titrate against 0.1N NaOH End point when fine pink color appear

32 Titration of Adrenaline
Calculation 1ml 0.1N NaOH mg Phenobarbitals Limitation 101% -98,5%

33 potentiometric curve

34 Safety Crystal violet glacial acetic acid
may cause cancer. Severe eye irritant. Harmful by inhalation, ingestion and through skin contact. Perchloric acid It is very corrosive to skin and eyes, It can also ignite or explode upon contact with organic material such as cloth or wood also Causes hypothyroidism digestive and respiratory tract burns& it is Corrosive to metal glacial acetic acid This material is strongly corrosive and causes serious burns. Very harmful if swallowed. Lachrymator

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