this slide is on common knowledge about impurities and its source in organic synthesis

1. Wait……

2. TOPIC:
IMPURITIES AND IT’S SOURCES IN
ORGANIC SYNTHESIS
Presented for:
Ph.D Course work
Presented by:
Subhash Vinod Jha

3. INTRODUCTION
This presentation is made to know about the impurities and
its impact in organic synthesis.
 Impurities are undesired which is obvious to generate
during synthesis.
 Impurities reduces the possibility of crystallization.
 Generally impurities have no value (waste).
 But in pharmaceutical field, isolated impurities have
higher value to identify the percentage and it impact on
human life while presence in drug substance.

4. Classification of impurities
Impurities can be classified in the following categories:
1. Organic impurities.
2. Inorganic impurities.
3. Residual solvents.

5. 1. Organic Impurities
Organic impurities can arise during the synthesis process
and storage of the substance. They can be identified or
unidentified, Volatile or Non volatile, are includes:
 Starting materials.
 By products.
 Intermediates.
 Reagents, ligands and Catalyst.

6. 2. Inorganic Impurities
Inorganic impurities can result in the manufacturing
process:
 Reagents, ligands and metal catalysts.
 Heavy metals or other residual metals.
 Inorganic slats
 Other materials (filter aids and charcols)

7. 3. Residual solvents
Residual solvents are define as a organic volatile or
Non volatile chemicals that may trapped in very small
quantity in the compound though it was concentrated.
• Residual solvents limitation for pharmaceutical
molecules are mentioned in ICH Q3C guideline.
• It may effect the stability of the compound and leads
for the compound degradation.

8. Source of impurities
 Things we added during preparation (Intentional):
Solvent, metal catalysts, Starting materials and reagents.
 Things we unintentionally add during Preparation:
Starting material impurities, Solvents impurities, reagents
impurities…
 Unwanted things that are made during preparation.
Reaction intermediates and related substances.
 Things that are formed after Preparation.
Degradation products.

9. Flow chart:
Potential impurities.
Reaction stages.
SM
Reaction
intermediate
Final
product
Reagents
Solvents
Catalysts
Degradation
By-products
By-products
SM
impurities
Reagents
Solvents
Catalysts

10. Classification of impurities as per pharma aspects.
Impurities further classified and its terminology used
for pharma aspects are:
 Impurity profile.
 Potential impurity.
 Identified impurity.
 Unidentified impurity.
 Specified impurity.
 Unspecified impurity.
 Stereospecific impurity.

11. Impurities Removing techniques.
Impurities can be remover by various techniques like:
 Filtration/Separation
 Distillation/Drying
 Isolation/precipitation
 Chromatography

12. Rough Idea about work-up of reaction mass.
Quenching (reagents and catalyst deactivate)
If any precipitation observe then filter it other wise
concentration (volatile impurity remove)
Extract compound in hydrophobic solvent and wash with
water, brine and bicarbonate wash, sodium sulphate
treatment and concentration (water soluble impurities
remove)
Purification by column chromatography/ Crystallization/
acid-base precipitation/ if product is liquid the high
vacuum distillation is preferable (to remove organic
impurities)
Dry the product under vacuum and store in airtight
container 2-8°C.
Reaction mass
Reaction mass
Organic mass
Crude mass
Pure prod.