Development and validation of novel LC-MS/MS method for determination of Lusutrombopag in rat plasma and its application to pharmacokinetic studies

摘要

A novel, simple and sensitive method for the determination of Lusutrombopag in rat plasma using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated. The determination was performed on an API4000 triple quadrupole mass spectrometry in the multiple reaction monitoring mode using the respective [M+H](+) ions m/z 593.1 -> 272.3 for Lusutrombopag. The limit of detection was 0.5 ng/mL, and the lower limit of quantification was 2.0 ng/mL in rat plasma. Good linearity was obtained over the range of 2.01-50.0 ng/mL and the correlation coefficient was found to be 0.9998. The intra and inter-day precisions were found to be 3.8-6.9% and 6.8-10.5%, respectively. The intra and inter-day accuracy derived from QC samples was found to be 2.5-4.9% and 5.5-7.2%, respectively. The analyte was stable under various conditions (at room temperature, during freeze-thaw, in the autosampler and under deep-freeze conditions). The F-test and t-test at 95% confidence level were subjected on data for statistical analysis. The developed method was successfully applied to the pharmacokinetic study in rats. (C) 2019 Production and hosting by Elsevier B.V. on behalf of King Saud University.