Application of one-step liquid chromatography-electrospray tandem MS/MS and collision-induced dissociation to quantification of ezetimibe and identification of its glucuronated metabolite in human serum: A pharmacokinetic study

作者：Bahrami Gholamreza^*; Mohammadi Bahareh; Khatabi Pyman Malek; Farzaei Mohammad Hosein; Majnooni Mohammad Bagher; Bahoosh Saba Rahimi

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2010, 878(28): 2789-2795.

DOI：10.1016/j.jchromb.2010.08.023

• HPLC
• Ezetimibe
• Ezetimibe glucuronide
• MRM
• LC-MS/MS bioequivalence study

A new one-step liquid chromatography-electrospray tandem MS/MS method is described to quantify ezetimibe (EZM) a novel lipid lowering drug in human serum. Also using collision-induced dissociation (CID) of the analyte, identification and chromatographic separation of its major metabolite, ezetimibe glucuronide (EZM-G) is achieved in this study. A thawed serum aliquot of 100 mu L was deproteinated by addition of 500 mu L methanol containing omeprazole as internal standard (I.S.). Separation of the drug, its metabolite and the I.S. were achieved using acetonitrile-water (70:30, v/v) as mobile phase at flow rate of 0.5 mL/min on a MZ PerfectSil target C18 column. Multiple reaction monitoring (MRM) mode of precursor-product ion transition (408.7 -> 272.0 for EZM and 345 -> 194.5 for the I.S.) was applied for detection and quantification of the drug while, EZM-G was chromatographically separated and identified using CID. The analytical method was linear over the concentration range of 1-32 ng/mL of EZM in human serum with a limit of quantification of 1 ng/mL. The coefficient variation values of both inter- and intra-day analysis were less than 8% whereas the percentage error was less than 3.7. The validated method was applied in a randomized cross-over bioequivalence study of two different EZM preparations in 24 healthy volunteers.

• 出版日期2010-10-15