摘要
目的:建立反相高效液相色谱-质谱法同时测定人血浆巾文拉法新(VEN)及其主要代谢产物氧去甲基文拉法新(ODV)对映体的浓度。方法:使用万古霉素手性柱(CHRIOBIOTIC V^(TM))(250 mm×4.6 mm,5 μm),以甲醇-醋酸铵缓冲液(30 mmol·L^(-1))(15:85,pH 6.0)为流动相对两化合物进行手性拆分,流速设为1.0 mL·min^(-1),柱后分流比为3:1。采用质谱电喷雾电离正源(ESI^+)将样品离子化,选择性离子监测(SIM)准分子离子峰。结果:在所建立的色谱条件下,VEN 与 ODV得到很好的手性分离。S-(+)与 R-(-)-VEN 在5.0～400 ng·mL^(-1)S-(+)与 R-(-)-ODV 在4.0～300 ng·mL^(-1)范围内线性关系良好,相关系数均大于0.9991;萃取回收率均大于76%;方法回收率均大于92%;最低检测浓度:S-(+)与R-(-)-VEN 为1.0 ng·mL^(-1),S-(+)与 R-(-)-ODV 1.5ng·mL^(-1);日内及日间 RSD 均小于9%。结论:本方法简单、快速、灵敏、准确,可用于 VEN 人体内立体选择性代谢的研究。
Objective ： To establish an HPLC - MS/ESI method for simultaneous stereoselective analysis of venlafaxine（VEN） and its major metabolite O- desmethylvenlafaxine （ODV） enantiomers in human plasma. Method：The CHRIOBIOTIC vTM（250 mm ×4. 6 mm,5μm） column was used with mobile phase constituted of 30 mmol · L^-1 ammonium acetate - methanol （85：15, pH 6.0） with a flow rate of 1.0 mL · min^-1 and the postcolumn splitting ratio was 3： 1. The compounds were ionized in the electrospray ionization （ESI） ion source of the mass spectrometer and detected in the selected ion recording （SIR） mode. Result：The enantiomers of VEN and ODV were completely separated under the present method. Calibration curves in spiked plasma were linear from 5.0 - 400 ng · mL^ - 1 for S -（ ＋）-VENandR-（-） -VEN,4.0-300 ng. mL-lforS-（ ＋）-ODV and R-（-） -ODV,respectively. All of them with coefficients of determination above 0. 9991. The average extraction recoveries for all the four analytes were above 76%. The methodology recoveries were higher than 92%. The limit of detection were 1.0 ng · mE^-1 for S- （ ＋ ） -VEN and R- （ - ） -VEN,1.5 ng · mL^-1 for S- （ ＋ ） -ODV and R - （ - ） - ODV,respectively. The intra - day and inter - day relative standard deviations were less than 9%. Condusion： The method is accurate, sensitive and reliable for the stereoselective metabolism study of the VEN in human plasma.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2008年第2期211-215,共5页
Chinese Journal of Pharmaceutical Analysis
