Lerch C, Blaschke G
Institute of Pharmaceutical Chemistry, University of Münster, Germany.
J Chromatogr B Biomed Sci Appl. 1998 Apr 24;708(1-2):267-75. doi: 10.1016/s0378-4347(97)00638-5.
Two different separation methods for the antischistosomal drug praziquantel and its metabolites by capillary electrophoresis are described. Achiral separation was obtained by micellar electrokinetic capillary chromatography using sodium dodecyl sulfate as micelle-forming surfactant. On the other hand, the negatively charged sulfobutylether-beta-cyclodextrin as a chiral selector enabled the separation of the drug and its metabolites as well as their enantioseparation. Based on this separation, the enantioselectivity of the metabolism of praziquantel was studied by incubation of the drug with rat liver microsomes. Whereas trans- and cis-4-hydroxypraziquantel were mainly formed from the R-(-)-enantiomer, another, different monohydroxylated metabolite was only formed from the S-(+)-enantiomer. Information about the structure of these metabolites was obtained, using LC-MS.
本文描述了两种通过毛细管电泳分离抗血吸虫药物吡喹酮及其代谢物的不同方法。使用十二烷基硫酸钠作为胶束形成表面活性剂，通过胶束电动毛细管色谱法实现了非手性分离。另一方面，带负电荷的磺丁基醚-β-环糊精作为手性选择剂，能够分离该药物及其代谢物以及它们的对映体。基于这种分离方法，通过将药物与大鼠肝微粒体孵育，研究了吡喹酮代谢的对映选择性。反式和顺式-4-羟基吡喹酮主要由R-(-)-对映体形成，而另一种不同的单羟基化代谢物仅由S-(+)-对映体形成。利用液相色谱-质谱联用技术获得了这些代谢物的结构信息。
