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DrX Whiz Niraj
Impurities & Limit Tests: Complete Principles
Master the foundational concepts of Inorganic Chemistry. Detailed notes on the History of Pharmacopoeia, Sources of Impurities, and Principles of all Major Limit Tests.
A Pharmacopoeia (Greek: Pharmakon = drug, poiein = to make) is an official legal document published by a recognized authority (usually the government) that contains the list of drugs, their formulas, standards for identity, purity, and strength.
Indian Pharmacopoeia (IP)
Published by the Indian Pharmacopoeia Commission (IPC).
First Edition: 1955.
The latest edition provides highly updated standards for Indian drugs.
British Pharmacopoeia (BP)
First published in 1864 by merging London, Edinburgh, and Dublin pharmacopoeias. Widely used in the UK and commonwealth nations.
United States Pharmacopeia (USP)
First published in 1820. Often combined with the National Formulary as USP-NF. Sets global rigorous standards.
An Impurity is defined as any unwanted, foreign chemical substance present in a pharmaceutical product. Impurities can make the drug toxic, alter its physical appearance, or reduce its therapeutic efficacy.
Common Sources of Impurities:
- 1. Raw Materials: Traces of heavy metals (Arsenic, Lead) naturally present in ores or plant extracts.
- 2. Reagents & Solvents: Tap water contains Calcium, Magnesium, and Chloride ions. Hence, Purified Water is used.
- 3. Manufacturing Process: Unreacted intermediates, by-products, or degradation products during synthesis.
- 4. Equipment Wear & Tear: Iron particles or grease from stainless steel manufacturing machines.
- 5. Packaging & Storage: Alkali leaching from cheap glass containers, or plasticizers leaking from plastic bottles.
Definition: Limit tests are quantitative or semi-quantitative tests designed to identify and control small quantities of specific impurities which are likely to be present in the pharmaceutical substance.
Principle: Almost all limit tests involve comparing the Opalescence (Turbidity) or Color produced by a Test solution with that of a Standard solution of known concentration. This is performed in identical glass tubes called Nessler Cylinders.
| Limit Test For | Main Reagent Used | Observation & Principle |
|---|---|---|
| 1. Chloride | Silver Nitrate (AgNO₃) in the presence of Dilute HNO₃ | Formation of Silver Chloride (AgCl) which produces Opalescence (turbidity). HNO₃ prevents precipitation of other acid radicals. |
| 2. Sulphate | Barium Chloride (BaCl₂) in the presence of Dilute HCl | Formation of Barium Sulphate (BaSO₄) producing Turbidity. HCl prevents precipitation of other barium salts. |
| 3. Iron | Thioglycolic acid in the presence of Ammonia | Thioglycolic acid reduces Fe³⁺ to Fe²⁺, forming a Ferrous thioglycolate complex having a Pale Pink to Deep Reddish-Purple color. |
| 4. Lead | Dithizone (Diphenylthiocarbazone) reagent | Lead forms a complex with Dithizone in alkaline medium, giving a Red color that is extracted in Chloroform. |
| 5. Heavy Metals | Hydrogen Sulphide (H₂S) or Thioacetamide solution | Heavy metals (like Pb, Hg, Bi) react to form metallic sulphides, producing a Brown/Black color. |
The Limit Test for Arsenic is highly specific and is based on the Gutzeit Test. It does NOT use Nessler cylinders.
AsH₃ + Mercuric Chloride Paper (HgCl₂) → Yellow Stain
Why Modified Limit Tests? Standard limit tests fail for intensely colored compounds (like Potassium Permanganate, KMnO₄) or highly insoluble substances. The color masks the opalescence/turbidity.
- Example (KMnO₄): Before performing the limit test for chloride or sulphate, the intensely purple KMnO₄ is first reduced using Ethanol to form a colorless precipitate of MnO₂, which is filtered out. The clear, colorless filtrate is then used for the standard limit test.
Practical Alert: What does (*) mean in the syllabus?
In your PCI syllabus, compounds marked with an asterisk (*) require you to memorize their Assay procedure (Quantitative determination of purity). Example: Assay of Sodium Bicarbonate (Acid-base titration), Assay of Copper Sulphate (Iodometry).