Abstract

METHOD DEVELOPMENT AND VALIDATION STUDY FOR QUANTITATIVE DETERMINATION OF CHLORO AND SULFIDE COMPOUND GENOTOXIC IMPURITIES IN ESOMEPRAZOLE ACTIVE PHARMACEUTICAL INGREDIENT (API) BY LC/MS/MS

Noor Shabana and K.Dayananda Reddy*

ABSTRACT

A simple, sensitive and rapid LC- ESI-MS/MS method has been developed and validated for the trace analysis (>1 ppm level) of 2-chloromethyl-4-methanesulfonyl-3, 5-dimethylpyridine hydrochloride (chloro) and 2-({[3,5-dimethyl-4-(methylsulfonyl)pyridi-2-yl]methyl} sulfanyl)-5-methoxy-1H-Benzimidazole (sulfide) compounds are genotoxic impurities, in esomeprazole magnesium drug. The chromatographic separation was achieved on a Hypersil BDS C8 (50 x 4.6mm, 3μm) column using a mobile phase consisting of 5mM ammonium acetate, methanol and acetonitrile (65:20:15, v/v/v) at flow rate of 0.6 mL/min. The API-4000 LC-MS/MS was operated on an electrospray ionization equipped with an ESI interface operated in positive ionization mode. The multiple-reaction monitoring (MRM) mode was used during the analytical run and it is able to quantitate up to 0.15 and 0.06 ppm of chloro and sulfide compound impurities. The newly developed method was validated as per International Conference on Harmonization (ICH) guidelines.

Keywords: Esomeprazole magnesium, Impurities, Method Validation, LC-ESI-MS/MS, Trace analysis.