Wang C P, Howell S R, Scatina J, Sisenwine S F
Drug Metabolism Division, Wyeth-Ayerst Research, Princeton, New Jersey 08543.
Chirality. 1992;4(2):84-90. doi: 10.1002/chir.530040204.
A stereospecific high-performance liquid chromatographic (HPLC) method was developed for the quantitation of the enantiomers of venlafaxine, an antidepressant, in dog, rat, and human plasma. The procedure involves derivatization of venlafaxine with the chiral reagent, (+)-S-naproxen chloride, and a postderivatization procedure. The method was linear in the range of 50 to 5,000 ng of each enantiomer per ml of plasma. No interference by endogenous substances or known metabolites of venlafaxine occurred. Studies to characterize the disposition of the enantiomers of venlafaxine were conducted in dog, rat, and human, following oral administration of venlafaxine. The Cmax, area under the curve (AUC) and (S)/(R) concentration ratios of the (R)- and (S)-enantiomers were compared. In rats, the mean plasma ratio of (S)-venlafaxine to that of (R)-venlafaxine over 0.5 to 6.0 h varied from 2.97 to 8.50 with a mean value of 5.51 +/- 2.45. The Cmax, AUC0-infinity, and t 1/2 values of the (R)- and (S)-enantiomers in dogs were not significantly different from one another (P greater than 0.1). The mean ratios [(S)/(R)] of enantiomers of venlafaxine in human over a 2 to 6 h interval ranged from 1.33 to 1.35 with an overall ratio of 1.34 +/- 0.26 (n = 12). These ratios of the enantiomers [(S)/(R)] were not statistically different from unity (P greater than 0.1) indicating that the disposition of venlafaxine enantiomers in humans is not stereoselective and is more similar to that in dogs than that in rats.
建立了一种立体专一性高效液相色谱（HPLC）法，用于定量测定犬、大鼠和人血浆中抗抑郁药文拉法辛对映体的含量。该方法包括用手性试剂（+）-S-萘普生氯对文拉法辛进行衍生化以及衍生化后处理步骤。该方法在每毫升血浆中每种对映体50至5000 ng的范围内呈线性。未出现内源性物质或文拉法辛已知代谢物的干扰。在犬、大鼠和人身上口服文拉法辛后，进行了文拉法辛对映体处置特征的研究。比较了（R）-和（S）-对映体的Cmax、曲线下面积（AUC）以及（S）/（R）浓度比。在大鼠中，0.5至6.0小时内（S）-文拉法辛与（R）-文拉法辛的平均血浆比值在2.97至8.50之间变化，平均值为5.51±2.45。犬体内（R）-和（S）-对映体的Cmax、AUC0至无穷大以及t 1/2值彼此之间无显著差异（P大于0.1）。在人类中，文拉法辛对映体在2至6小时内的平均比值[（S）/（R）]在1.33至1.35之间，总体比值为1.34±0.26（n = 12）。这些对映体比值[（S）/（R）]与1无统计学差异（P大于0.1），表明文拉法辛对映体在人体内的处置无立体选择性，且与犬体内的情况比与大鼠体内的情况更相似。
