Boursier-Neyret C, Baune A, Klippert P, Castagne I, Sauveur C
Bio-Pharmacie Servier, Orléans, France.
J Pharm Biomed Anal. 1993 Nov-Dec;11(11-12):1161-6. doi: 10.1016/0731-7085(93)80099-m.
S 12024-2 is a new drug in phase II development that possesses cognitive enhancing properties. As its molecular structure has a chiral centre, a stereoselective method for the analysis of both enantiomers in human plasma has been developed. The method involves pre-column derivatization of the amine moiety with a homochiral reagent (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC), and chromatographic separation of the two diastereoisomers on an achiral reversed-phase cyanopropyl column, with fluorimetric detection (lambda ex = 260 nm; lambda em = 310 nm). A liquid-liquid extraction procedure with diethyl ether-dichloromethane (70:30, v/v) was used for sample preparation. This technique provides a linear response for both enantiomers over a concentration range of 10-500 ng ml-1 and the quantitation limit was set at 5 ng ml-1 in human plasma. Within-day and between-day precision and accuracy are within 9% limits for all concentrations assessed. This procedure was therefore used for determining both enantiomers in human plasma following oral administration of racemic S 12024-2 to elderly healthy subjects.
S 12024-2是一种处于II期开发阶段的具有认知增强特性的新药。由于其分子结构具有一个手性中心，已开发出一种用于分析人血浆中两种对映体的立体选择性方法。该方法包括用同手性试剂（+）-1-（9-芴基）乙基氯甲酸酯（FLEC）对胺部分进行柱前衍生化，以及在非手性反相氰丙基柱上对两种非对映异构体进行色谱分离，并采用荧光检测（激发波长λex = 260 nm；发射波长λem = 310 nm）。采用乙醚-二氯甲烷（70:30，v/v）液-液萃取程序进行样品制备。该技术在10 - 500 ng ml-1的浓度范围内对两种对映体均提供线性响应，人血浆中的定量限设定为5 ng ml-1。在所评估的所有浓度下，日内和日间精密度与准确度均在9%的限度内。因此，该程序用于在老年健康受试者口服消旋S 12024-2后测定人血浆中的两种对映体。
