Dieterle W, Faigle J W
J Chromatogr. 1982 Jun 25;242(2):289-97. doi: 10.1016/s0021-9673(00)81703-3.
An isotope dilution assay for the determination of both oxaprotiline enantiomers in biological samples after administration of the racemic mixture has been developed. The enantiomers were reacted with synthetically prepared, optically pure N-trifluoroacetyl-S(-)-prolyl chloride, followed by high-performance liquid chromatographic separation of the diastereoisomers formed. Quantitation was performed by on-line UV detection at 260 nm and off-line radiometry by liquid scintillation counting. Endogenous compounds and metabolites do not interfere in the assay. Analysis of water and the blood and urine of rats spiked with [14C]oxaprotiline X HCl showed recoveries for S(+)-oxaprotiline X HCl (mean +/- coefficient of variation, n = 4-6) of 98.0 +/- 1.0% (water), 100.5 +/- 0.6% (blood) and 101.5 +/- 2.0% (urine), and for R(-)-oxaprotiline X HCl of 101.3 +/- 2.0% (water), 102.2 +/- 2.1% (blood) and 103.2 +/- 0.2% (urine). A pilot study to determine blood levels of the two enantiomers in two rats dosed with racemic [14C]oxaprotiline X HCl (10 mg/kg i.v.) was carried out to test the method. The results indicated stereoselective disposition of oxaprotiline enantiomers in the rat. The ratio of the areas under the blood concentration curves for R(-)-to S(+)-oxaprotiline X HCl was 1.14.
已开发出一种同位素稀释分析法，用于测定外消旋混合物给药后生物样品中奥沙普明两种对映体的含量。对映体与合成制备的光学纯N - 三氟乙酰基 - S(-)-脯氨酰氯反应，然后对形成的非对映异构体进行高效液相色谱分离。通过在260 nm处的在线紫外检测和通过液体闪烁计数进行的离线放射测量法定量。内源性化合物和代谢物不干扰该分析。对添加了[14C]奥沙普明X盐酸盐的大鼠的水、血液和尿液进行分析，结果显示S(+)-奥沙普明X盐酸盐（平均值±变异系数，n = 4 - 6）在水中的回收率为98.0±1.0%，在血液中的回收率为100.5±0.6%，在尿液中的回收率为101.5±2.0%；R(-)-奥沙普明X盐酸盐在水中的回收率为101.3±2.0%，在血液中的回收率为102.2±2.1%，在尿液中的回收率为103.2±0.2%。进行了一项初步研究，以测定两只静脉注射外消旋[14C]奥沙普明X盐酸盐（10 mg/kg）的大鼠体内两种对映体的血药浓度，以测试该方法。结果表明奥沙普明对映体在大鼠体内的处置具有立体选择性。R(-)-与S(+)-奥沙普明X盐酸盐血药浓度曲线下面积之比为1.14。
