1st Year • ER20-12T
Pharmaceutical Chemistry: Inorganic & Organic Drug Guide
Compiled by Dr. Sunita Sharma, M.Pharm (Ph.D)
Chapter 1: Impurities in Pharmaceutical Substances
An impurity is any chemical substance present in a pharmaceutical product that is not the active therapeutic moiety or an intended excipient.
Sources of Impurities:
- Raw Materials: Unreacted starting materials, ores (e.g., Arsenic in mined rock salt used to prepare Sodium Chloride).
- Manufacturing Process: Reagents, catalysts, reaction vessels, solvents.
- Chemical Instability: Decomposition during shelf life, oxidation, photolysis, hydrolysis.
- Cross-Contamination: Particulate matter, cleaning agents, packaging leaching.
Chapter 2: Limit Tests in Pharmacopoeia
A limit test is a semi-quantitative test designed to identify and control small quantities of inorganic impurities present in pharmaceutical substances by visual comparison with a known standard.
2.1 Limit Test for Chlorides (IP)
Principle: Based upon the precipitation reaction between soluble chloride ions and silver nitrate reagent in the presence of dilute nitric acid to form opalescent Silver Chloride precipitate:
Cl⁻ + AgNO₃ → AgCl ↓ (White Opalescence) + NO₃⁻
Dilute nitric acid prevents precipitation of other acid-soluble silver salts like Silver Phosphate or Silver Carbonate.
2.2 Limit Test for Arsenic (Gutzeit Apparatus)
Arsenic impurity is converted into yellow-brown stains on Mercuric Chloride (HgCl₂) paper by Arsenic hydride (Arsine gas, AsH₃).
Key Reagents & Roles:
- Granulated Zinc & HCl: Generate nascent hydrogen (H₂).
- Potassium Iodide (KI) & Stannous Chloride (SnCl₂): Reduce pentavalent Arsenic (As⁵⁺) to trivalent Arsenious acid (As³⁺).
- Lead Acetate Soaked Cotton Plug: Traps any Hydrogen Sulfide (H₂S) gas produced, preventing false blackening of mercuric chloride test paper.