LC-MS/MS METHOD FOR SIMULTANEOUS DETERMINATION OF VALPROIC ACID AND MAJOR METABOLITES IN HUMAN PLASMA
A rapid and sensitive method using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) was developed and validated for simultaneous quantitative determination of valproic acid and three major metabolites (3-OH-valproic acid, 4-ene-valproic acid and 5-OH-valproic acid) in human plasma. Methods:The analytes and internal standard were isolated from 200μL samples by solid phase extraction using a ZORBAX SB-C8 column (3.5 μm, 2.1 × 100 mm) with an isocratic mobile phase consisting of methanol-10mM ammonium acetate (80:20, v/v)containing 0.1% formic acid at a flow rate of 0.3 mL/min. The method had a chromatographic total run time of 2.0 min. The Agilent G6410A triple quadrupole LC/MS system was operated under a multiple reaction monitoring and single ion monitoring mode using the electrospray ionization technique in a negative mode. Results:The lower limit of quantification of valproic acid, 3-OH-valproic acid, 4-ene-valproic acid and 5-OH-valproic acid of the method was 2030, 51.5, 50.15 and 51.25 ng/mL, respectively. The method was linear for valproic acid and the three metabolites with correlation coefficients > 0.995 for all analytes. The intra-day andinter-day accuracy and precision of the assay were less than 15.0%. Conclusions:This analytical method was successfully used to assay plasma concentrations of valproic acid and the three metabolites in human plasma from epileptic patients.
丙戊酸 代谢产物 人血浆 癫痫患者 液相色谱串联质谱
Gao Shouhong Miao Haijun Chen Wansheng
Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003 ,PR China
国内会议
烟台
英文
1-19
2011-11-01(万方平台首次上网日期,不代表论文的发表时间)