Prakash C, Koshakji R P, Wood A J, Blair I A
Department of Pharmacology, Vanderbilt University, School of Medicine, Nashville, TN 37232.
J Pharm Sci. 1989 Sep;78(9):771-5. doi: 10.1002/jps.2600780915.
A simple, rapid, and sensitive assay for the simultaneous quantification of the (-)- and (+)-propranolol in human and dog plasma is described using a reversed-phase high-performance liquid chromatography (HPLC) system with fluorescence detection. The method involves extraction of propranolol enantiomers from plasma into 1% 1-butanol in n-hexane at basic pH, followed by evaporation of the organic phase and the formation of diastereomeric derivatives with the chiral reagent (-)-menthyl chloroformate. (+)-Flecainide is used as the internal standard. The limiting concentration of each enantiomer that can be detected is 1 ng/mL plasma. In six normal human volunteers, who received a single oral dose of 80 mg of racemic propranolol, the plasma levels of the (-)-enantiomer were always higher than those of the (+)-enantiomer with a mean (-):(+) ratio of 1.38. The half-lives of both the enantiomers were similar (3.5 +/- 0.3 h). In six normal male mongrel dogs given a single intraportal dose of 40 mg of racemic propranolol, the plasma levels of the (-)-enantiomer were always lower than those of the (+)-enantiomer with a mean (-):(+) ratio of 0.48. The half-life of the (-)-enantiomer (73.3 +/- 16.2 min) was shorter than that of the (+)-enantiomer (87.1 +/- 18.1 min).
描述了一种使用带荧光检测的反相高效液相色谱（HPLC）系统，同时定量人血浆和犬血浆中（-）-和（+）-普萘洛尔的简单、快速且灵敏的分析方法。该方法包括在碱性pH条件下，将血浆中的普萘洛尔对映体萃取到正己烷中的1%正丁醇中，然后蒸发有机相，并与手性试剂（-）-氯甲酸薄荷酯形成非对映体衍生物。（+）-氟卡尼用作内标。可检测的每种对映体的极限浓度为1 ng/mL血浆。在6名单次口服80 mg消旋普萘洛尔的正常人类志愿者中，（-）-对映体的血浆水平始终高于（+）-对映体，平均（-）:（+）比值为1.38。两种对映体的半衰期相似（3.5±0.3小时）。在6只单次门静脉注射40 mg消旋普萘洛尔的正常雄性杂种犬中，（-）-对映体的血浆水平始终低于（+）-对映体，平均（-）:（+）比值为0.48。（-）-对映体的半衰期（73.3±16.2分钟）短于（+）-对映体（87.1±18.1分钟）。
