A Validated, Specific, Stability-Indicating RP-LC Method for Analysis of Gatifloxacin in the Presence of Degradation Products and Process-Related Impurities

摘要

A validated, specific, stability-indicating reversed-phase liquid chromatographic method has been developed for quantitative analysis of gatifloxacin, its degradation products, and its process-related impurities in bulk samples and in pharmaceutical dosage forms. Forced degradation of gatifloxacin bulk sample was conducted in accordance with ICH guidelines. Acidic, basic, neutral, and oxidative hydrolysis, thermal stress, and photolytic degradation were used to assess the stability-indicating power of the method. Substantial degradation was observed during oxidative hydrolysis. No degradation was observed under the other stress conditions. The method was optimized using samples generated by forced degradation and sample solution spiked with impurities. Good resolution of the analyte peak from peaks corresponding to process-related impurities and degradation products was achieved on a C₁₈ column by use of a simple linear mobile-phase gradient prepared from mixtures of acetonitrile and an aqueous solution of sodium dihydrogen orthophosphate dihydrate and triethylamine adjusted to pH 6.5 with orthophosphoric acid. Detection was performed at 240 nm. Limits of detection and quantification were established for gatifloxacin and its process-related impurities. When the stressed test solutions were assayed by comparison with gatifloxacin working standard the mass balance was always close to 99.3%, indicating the method was stability-indicating. Validation of the method was performed in accordance with ICH requirements. The method was found to be suitable for checking the quality of bulk samples of gatifloxacin at the time of batch release and also during storage. Keywords Column liquid chromatography - Forced degradation - Gatifloxacin