impurities source of impurities: 1.during synthesis 2.during manufacturing 3.during storage

Impurities

Source of impurities:1. During synthesis

2. During manufacturing

3. During storage

Impurities

Classification of chemicals :

1. Commercial chemicals

2. Pure chemicals

3. Analytical chemicals

4. Pharmaceutical chemicals

Pharmacopoeia

• A description of the article• Tests for identity• Physical constants• Quantitative assay• Limit test Storage conditions

official = obey the requirement

Pharmacopoeia

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

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

Limit test

Type:

1. Comparison method

2. Quantitative determination

3. Test in which there is no visible reaction

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)

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

Limit test

General precaution1. The liquid used must be clean and filtered if

necessary 2. The Nessler cylinder must be made of colorless

glass and of the same inner diameter3. Detecting opalescence or color development must

be performed in daylight 4. When comparing turbidity it should be done

against black background5. When comparing color it should be done against

white background

Limit test

Limit Test for Ammonium

Principle

NH4+ + K2HgI4 NH2Hg2I3

10ml of standard NH4+ (1ppm)

+5ml H2O

Add dis. water to 50 ml

0.3ml Nessler reagent

15ml sample solution

Add dist. water to 50 ml

0.3ml Nessler reagent

Limit Test for Chloride

Principle:

AgClCl- + AgNO3

15ml sample

1ml HNO3

Dist. H2O to 50 ml

1ml AgNO3

10ml St Cl- (5ppm) +5ml H2O

1ml HNO3

Dist. H2O to 50ml

1ml AgNO3

Limit Test of Sulphate

Principle:

SO4-2 + BaCl2 BaSO4

1ml 25%BaCl2

1.5ml ethanolic SO4standardMIX by rotation&

wait for 1 minute

15ml Standard 15ml sample

15ml water

Mix by rotation

Add 0.5ml acetic acid(5M

Complete volume with Dil.water to 50ml

Limit Test for Iron

5ml NH4SCN

H2O to 50ml

5ml HNO3

10ml sample

5ml NH4SCN

H2O to 50ml

5ml HNO3

10ml standard

Principle:

Fe+3 + NH4SCN Fe(SCN)3

Procedure:

Why we use nitric acid?

Limit Test of CalciumPrinciple:

Ca+2 + (NH4)2C2O4 CaC2O4

Procedure • 0.2ml alcoholic calcium stander(100ppm)

• 1ml ammonium oxalate 1 MIN

2ml calcium stander )100ppm(

20 ml dist water

Pipette 15 ml

1ml acetic acid

to 50ml with dist water

10ml calcium stander )10ppm(

5 ml dist water

Aspirin Limit Test of Salicylic Acid

• 0.05 ml FeCl3• to 50ml H2O

• 15 ml iced H2O • 0.1ml acetic acid

• 0.1gm sample • 5ml ethanol

•0.05 ml FeCl3• to 50ml H2O

•15 ml iced H2O •0.1ml acetic acid•1ml salicylic acid

•4ml ethanol

Limit Test of Heavy Metal

• 1.2ml thioacetamide • mix• 2ml acetate buffer • 12ml sample

•1.2ml thioacetamide

• mix •2ml acetate buffer• 10ml standard Pb•2ml sample

Principle:

Pb+2 +NaS PbS

Sample preparation

2.5g aspirin dissolve in 30ml

acetone then complete to 50

ml with H2O

Quantitative Limit Test

Determination of lead concentration in a sample of heavy metals

Primary solution Auxiliary solution

1ml sample

2ml standard

3ml standard4ml standard

3ml sample

5ml standard

1 ml NH4OH1 ml NH4OH

5drops thioacetmide5drops thioacetmide

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


Inert neutral substance as

:benzene , chloroform and

hydrocarbon

Non Aqueous Acid-Base TitrationProtic 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-


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-


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


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

Titration of Adrenaline

PrincipleHClO4 + CH3COOH CH3COOH2

+ + ClO4-

+ CH3COOH CH3COO- +

+ HClO4 + ClO4-


Volumetric:

1. In dry conical flask weigh 0.2g adrenaline2. Add 25ml glacial acetic acid3. One drop crystal violet indicator4. Titrate against perchloric acidPoteatiometric5. In dry beaker 0.2g adrenaline6. 25ml glecial acetic acid7. Titate against perchloric acid

End point when greenish blue appear

Add 0.5ml until near the E.P add 0.1ml


CalculationFrom the equivalent factor each ml of perchloric acid react

with 0.01832 of C9H13NO3

F= (molecular weight of sample*molarities of standard) 1000

• Theoretical (equivalent point) 1ml of 0.1M HClO4 0.01832g adrenaline X ml the weighted amount of

sample

X= equivalent point

0.2g adrenaline


Calculation

%of deviation= end point from the graph*100

equivalent point

Limitation 101% -98,5%

Titration of Phenobarbitals

• Principle

Titration of Phenobarbitals

• Volumetric titration 1. In dry conical flask weight 0.5g Phenobarbital

2. Add 40ml neutralized alcohol

3. Add 20 ml water

4. Titrate against 0.1N NaOH using ph.ph as indicator

• Potentiometric titration1. In a dry beaker weight 0.5g Phenobarbital

2. Add 40ml neutralized alcohol

3. Add 20 ml water

4. Titrate against 0.1N NaOH

End point when fine pink color appear

Add 3 drop of ph.ph to the alcohol then add sufficient

amount of NaOH (0.02 or0.1N) TO produce PINK

COLOR


• Calculation 1ml 0.1N NaOH 23.22mg Phenobarbitals

Limitation 101% -98,5%

potentiometric curve

Safety

• Crystal violet 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

impurities source of impurities: 1.during synthesis 2.during manufacturing 3.during storage

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