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
Principle

31. Titration of Phenobarbitals
Add 3 drop of ph.ph 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 ph.ph 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