Validation and Reproducibility of an LC–MS/MS Method for Emixustat and Its Three Deaminated Metabolites in Human Plasma

Aim: A sensitive method to quantify emixustat and its rapidly formed three major deaminated metabolites in human plasma was necessary to determine exposure in clinical trials. Methods: An LC–MS/MS method was validated for accuracy and precision, linearity, carry over, selectivity, recovery, matrix effects, hematocrit effects and stability. Results: A quantitative procedure for the determination of emixustat, ACU-5116, ACU-5124 and ACU-5149 in human plasma over the concentration range of 0.0500/1.00/1.00/1.00–10.0/1000/1000/1000 ng/ml, was successfully validated and has been used to successfully analyze samples in three clinical trials. Incurred sample reanalysis was performed for all four analytes in each study with >92% of the repeat results and original results within 20% of the mean of the two values.