Optimization of Bioanalytical Liquid Chromatography - Tandem Mass Spectrometric Method for Quantification of Tazemetostat: An Epithelioid Sarcoma Treatment Drug in Human Plasma

The pharmaceutical drug tazemetostat prevent spreading of cancer cells in adults and was available in the form of tablets in market. The literature reveals that, no analytical method reported for evaluation of tazemetostat in biological samples and hence this study planned to propose a simple and sensitive LCMS/MS method for quantification of tazemetostat in spiked plasma using vorinostat as internal standard. The extraction of tazemetostat along with vorinostat was performed using a simple protein precipitation followed by liquid-liquid extraction with dichloromethane. The Agilent eclipse plus C18 (100x4.6 mm, 3.5 μm) column with 0.1 % formic acid in water, 0.1 % formic acid in acetonitrile at 65:35 (v/v) pH 3.9 at 0.3 mL/min isocratic flow was optimized and finalized for resolution of tazemetostat and internal standard. The resolved analytes were monitored with mass analyser operated in multiple reaction monitoring positive ion mode. The characteristic mass transition at m/z 571→136 and m/z 265→94 was noticed for tazemetostat and vorinostat respectively. The method produces linear calibration curve in the concentration level of 0.1 - 400 ng/mL that suggest method sensitivity. The stability during handling, extraction and well as analysing the tazemetostat solution was evaluated by performing various stability studies. The analytes were confirmed to be acceptable in every studied stability studies. The validation study produces acceptable results in all parameters and can successfully utilized for evaluation of tazemetostat in biological samples.