Stability‐indicating method for quantification of potential genotoxic impurity and other organic impurities of chlorzoxazone using hyphenated techniques

Abstract

AbstractA simple, reliable, and stability‐indicating RP‐HPLC‐UV method was developed and validated for the estimation of related substances (p‐chlorophenol and unknown impurities) of chlorzoxazone (skeletal muscle relaxant). Along with this as the compound contains a potential genotoxic impurity (2‐amino‐4‐chlorophenol), which needs to have more sensitivity in quantification, we have also developed and validated a separate RP‐HPLC‐mass spectrometry (MS)/MS method for the estimation of 2‐amino‐4‐chlorophenol impurity. Both methods (RP‐HPLC‐UV & RP‐HPLC–MS/MS) were validated in accordance with International Council for Harmonization Q2(R1) and were found to be precise, accurate, robust, linear, and specific with limit of quantification values established with respect to 100% of test concentration, 0.018% w/w of p‐chlorophenol by RP‐HPLC‐UV, and 2 ppm of 2‐amino‐4‐chlorophenol by RP‐HPLC–MS.