Abstract: A sensitive,selective and simple liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for determining the major active metabolite 8′-hydroxy-dihydroergocryptine (8′-OH-DHEC) of α-dihydroergocryptine (DHEC) in human plasma.The analyte was extracted from plasma samples by liquid-liquid extraction,separated through a Shimadzu shim-pack VP-ODS column (150 mm×2.0 mm,5 μm) using isocratic mobile phase consisting of 0.1% formic acid- methanol (48 ∶52)，and analyzed by electro-spray ionization (ESI) in the selected reaction monitoring mode.The precursor to product ion transitions of m/z594.3→270.0 and m/z 264.1→58.3 were used to measure 8′-OH-DHEC and the IS tramadol，respectively.The method was validated over a concentration range of 50-4 000 pg/mL.The intra- and inter-day precision values were less than 10% and accuracy values 90%-110%.The stability of 8′-OH-DHEC in human plasma under different storage conditions met the requirements of bioanalytical method.The established method was successfully applied to a bioequivalence study after single oral administration of 4 mg DHEC mesilate (test and reference) in 22 healthy volunteers.The 90% confidence intervals of log‐transformed ratios of the c_maxand AUC_0-twere 89.68%-129.9%,106.9%-121.8%,respectively.The method is selective and suitable for the quantification of 8′-OH-DHEC in human plasma.