Determination of Dextrorphan in Human Liver Microsomes by LC-MS/MS / 医药导报

ABSTRACT

Objective To establish a liquid chromatographic-mass spectrometric method ( LC-MS/MS method ) for determination of dextrorphan in human liver microsome. Methods LC-MS/MS was adopted with carbamazepine serving as an internal standard.The separation was performed on Agilent ZORBAX XDB-C18 column (2.1 mm×50 mm, 3.5μm), with mobile phase consisting of 0. 05% formic acid methanol-0. 05% formic acid in gradient elution. Dextrorphan and carbamazepine were detected on multiple reaction monitoring(MRM)mode by transitions from precursor to production(m/z 258.1→199.1, 237.1→194.1). Results The linear range of dextrorphan concentration was 19.22-768 960 ng.L-1(r=0.999 8), and the lowest quantification limit was 19.22 ng.L-1.The relative recoveries were 94.02%-98.74%, and the RSDs of intra-day and inter-day were within 10%.IC50 of psoralen on CYP2D6 was 0.6μmol.L-1. Conclusion The LC-MS/MS method is proved to be rapid, sensitive and reproducible, psoralen is a strong inhibitor of CYP2D6.