Determination of Methyl Methanesulfonate and Ethyl Methylsulfonate in New Drug for the Treatment of Fatty Liver Using Derivatization Followed by High-Performance Liquid Chromatography with Ultraviolet Detection

A new derivatization high-performance liquid chromatography method with ultraviolet detection was developed and validated for the quantitative analysis of methanesulfonate genotoxic impurities in an innovative drug for the treatment of non-alcoholic fatty liver disease. In this study, sodium dibenzyldithiocarbamate was used as a derivatization reagent for the first time to enhance the sensitivity of the analysis, and NaOH aqueous solution was chosen as a pH regulator to avoid the interference of the drug matrix. Several key experimental parameters of the derivatization reaction were investigated and optimized. In addition, specificity, linearity, precision, stability, and accuracy were validated. The determined results of the samples were consistent with those obtained from the derivatization gas chromatography-mass spectrometry analysis. Thus, the proposed method is a reliable and practical protocol for the determination of trace methanesulfonate genotoxic impurities in drugs containing mesylate groups.

Automated summary

A new method using derivatization high-performance liquid chromatography with ultraviolet detection was developed and validated for the quantitative analysis of genotoxic impurities in a novel drug. The method was found to be reliable and practical through optimization and validation of key experimental parameters.