Simultaneous determination of hyzetimibe and its main active metabolite in plasma by LC–MS/MS and its application in PK study

Abstract

Background: Hyzetimibe is a new compound belonging to a novel class of selective cholesterol absorption inhibitors. A simple, highly sensitive LC–MS/MS method has been developed for the quantification of hyzetimibe and its main active metabolite, hyzetimibe-glucuronide, in human plasma. Results: Analytical samples were prepared using a protein precipitation method coupled with a concentration process. The linearity of this method was established for concentrations in the ranges of 0.05–50 and 0.5–500 ng/ml for hyzetimibe and hyzetimibe-glucuronide, respectively. The accuracy and precision of the method varied from 97.9 to 105% and 2.6 to 7.4%, respectively. Conclusion: This study represents the first reported example of an LC–MS/MS assay for the simultaneous quantification of hyzetimibe and its main active metabolite, hyzetimibe-glucuronide, in human plasma. Furthermore, this method has been successfully applied to a PK study.