Download - Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage
![Page 1: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/1.jpg)
![Page 2: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/2.jpg)
Impurities
Source of impurities:1. During synthesis
2. During manufacturing
3. During storage
![Page 3: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/3.jpg)
Impurities
Classification of chemicals :
1. Commercial chemicals
2. Pure chemicals
3. Analytical chemicals
4. Pharmaceutical chemicals
![Page 4: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/4.jpg)
Pharmacopoeia
• A description of the article• Tests for identity• Physical constants• Quantitative assay• Limit test Storage conditions
official = obey the requirement
![Page 5: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/5.jpg)
Pharmacopoeia
• British pharmacopoeia (BP)• European pharmacopoeia (Eu.Ph)• United state pharmacopoeia (USP)
![Page 6: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/6.jpg)
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
![Page 7: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/7.jpg)
Limit test
Type:
1. Comparison method
2. Quantitative determination
3. Test in which there is no visible reaction
![Page 8: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/8.jpg)
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)
![Page 9: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/9.jpg)
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
![Page 10: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/10.jpg)
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
![Page 11: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/11.jpg)
Limit test
![Page 12: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/12.jpg)
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
![Page 13: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/13.jpg)
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
![Page 14: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/14.jpg)
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
![Page 15: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/15.jpg)
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?
![Page 16: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/16.jpg)
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
![Page 17: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/17.jpg)
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
![Page 18: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/18.jpg)
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
![Page 19: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/19.jpg)
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
![Page 20: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/20.jpg)
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
![Page 21: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/21.jpg)
Non Aqueous Acid-Base Titration
Inert neutral substance as
:benzene , chloroform and
hydrocarbon
![Page 22: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/22.jpg)
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-
![Page 23: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/23.jpg)
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-
![Page 24: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/24.jpg)
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
![Page 25: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/25.jpg)
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
![Page 26: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/26.jpg)
Titration of Adrenaline
PrincipleHClO4 + CH3COOH CH3COOH2
+ + ClO4-
+ CH3COOH CH3COO- +
+ HClO4 + ClO4-
![Page 27: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/27.jpg)
Titration of Adrenaline
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
![Page 28: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/28.jpg)
Titration of Adrenaline
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
![Page 29: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/29.jpg)
Titration of Adrenaline
Calculation
%of deviation= end point from the graph*100
equivalent point
Limitation 101% -98,5%
![Page 30: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/30.jpg)
Titration of Phenobarbitals
• Principle
![Page 31: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/31.jpg)
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
![Page 32: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/32.jpg)
Titration of Adrenaline
• Calculation 1ml 0.1N NaOH 23.22mg Phenobarbitals
Limitation 101% -98,5%
![Page 33: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/33.jpg)
potentiometric curve
![Page 34: Impurities Source of impurities: 1.During synthesis 2.During manufacturing 3.During storage](https://reader038.vdocuments.mx/reader038/viewer/2022102900/5518c670550346b31f8b57f8/html5/thumbnails/34.jpg)
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