JNTU B.Pharmacy I PHARMACEUTICAL INORGANIC CHEMISTRY-I Previous Question Paper (June-2022 - R17)

Impurities in pharmaceutical substances arise from various sources during manufacturing, storage, and handling. The primary sources include:

1. Raw Materials: Impurities present in the starting materials or reagents used in synthesis. For example, lead or arsenic contamination in mineral acids.
2. Manufacturing Process: Contamination from equipment (e.g., heavy metals from stainless steel reactors) or residual solvents used in crystallization.
3. Chemical Instability: Degradation products formed due to exposure to light, heat, or moisture. For example, the hydrolysis of aspirin into salicylic acid.
4. Atmospheric Contamination: Exposure to dust, moisture, or gases like carbon dioxide during processing.
5. Storage Conditions: Interactions with packaging materials, such as leaching of plasticizers from containers or glass particles from ampoules.
6. Intermediate Products: Incomplete reactions leading to the presence of unreacted precursors or side-products in the final drug substance.

Principle: The limit test for arsenic is based on the Gutzeit test, where arsenic present in the sample is converted to arsine gas (AsH₃) by reaction with zinc and hydrochloric acid. The arsine gas reacts with mercuric chloride paper to produce a yellow-to-brown stain. The intensity of the stain is compared against a standard stain produced by a known amount of arsenic.

Reactions:

Procedure:

1. Prepare the Gutzeit apparatus consisting of a wide-mouthed bottle, a glass tube, and a rubber bung.
2. Place the sample (or standard arsenic solution) in the bottle and add hydrochloric acid and potassium iodide to reduce arsenic to the trivalent state.
3. Add granulated zinc to initiate the evolution of hydrogen gas, which reduces arsenic to arsine gas.
4. Place a piece of mercuric chloride paper at the top of the glass tube, ensuring the gas passes through it.
5. Allow the reaction to proceed for 40 minutes.
6. Compare the intensity of the stain produced on the test paper with the stain produced by the standard arsenic solution. The test is passed if the stain intensity of the sample is not greater than that of the standard.