Quantitative Determination of Synthesized Genotoxic Impurities in Nifuroxazide Capsules by Validated Chromatographic Methods

J AOAC Int. 2018 Mar 1;101(2):385-393. doi: 10.5740/jaoacint.17-0015. Epub 2017 Jul 31.

Abstract

Two accurate, selective, and precise chromatographic methods, namely TLC-densitometric and reversed-phase (RP)-HPLC, were developed and validated for the simultaneous determination of nifuroxazide (NIF) and its four synthesized impurities, which are also reported to be its related substances in the range of 10-100 μg/band and 10-100 μg/mL for NIF in the TLC and RP-HPLC methods, respectively. The developed TLC-densitometric method depended on the separation and quantitation of the studied components on silica gel 60 F254 TLC plates. Ethyl acetate-acetone-methanol-ammonia (85 + 25 + 5 + 0.5, v/v/v/v) was used as the developing system, and the separated bands were UV-scanned at 230 nm. On the other hand, the developed RP-HPLC method depended on chromatographic separation using a C8 column at 25°C and an aqueous solution of 0.1% sodium lauryl sulfate-acetonitrile as the mobile phase delivered according to the gradient elution program. Factors affecting the developed methods were studied and optimized. Also, method validation was carried out according to International Conference on Harmonization guidelines. The proposed methods were successfully applied for the determination of the studied drug in its bulk powder and in its pharmaceutical formulation. The developed methods showed no significant difference when compared with the reported RP-HPLC one. Their advantage is being the first stability-indicating methods for NIF and its genotoxic impurities.

MeSH terms

  • Capsules
  • Chromatography, Reverse-Phase / methods*
  • Chromatography, Thin Layer / methods*
  • Densitometry / methods*
  • Drug Contamination
  • Hydroxybenzoates / analysis*
  • Limit of Detection
  • Mutagens / analysis*
  • Nitrofurans / analysis*

Substances

  • Capsules
  • Hydroxybenzoates
  • Mutagens
  • Nitrofurans
  • nifuroxazide