Chen Xinxin, Gu Ermin, Wang Shuanghu, Zheng Xiang, Chen Mengchun, Wang Li, Hu Guoxin, Cai Jian-ping, Zhou Hongyu
Pharmacology Department, School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China.
The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Lishui 323000, China.
J Chromatogr Sci. 2016 Mar;54(3):334-42. doi: 10.1093/chromsci/bmv146. Epub 2015 Oct 24.
Oxcarbazepine (OXC), a second-generation antiepileptic drug, undergoes rapid reduction with formation of the active metabolite 10,11-dihydro-10-hydroxy-carbazepine (MHD) in vivo. In this study, a method for simultaneous determination of OXC and MHD in rat plasma using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS-MS) was developed and validated. Under given chromatographic conditions, OXC, MHD and internal standard diazepam were separated well and quantified by electrospray positive ionization mass spectrometry in the multiple reaction monitoring transitions mode. The method validation demonstrated good linearity over the range of 10-2,000 ng/mL for OXC and 5-1,000 ng/mL for MHD. The lower limit of quantification was 5 ng/mL for OXC and 2.5 ng/mL for MHD, respectively. The method was successfully applied to the evaluation of the pharmacokinetics of OXC and MHD in rats, with or without pretreatment by ketoconazole (KET) and voriconazole (VOR). Statistics indicated that KET and VOR significantly affected the disposition of OXC and MHD in vivo, whereas VOR predominantly interfered with the disposition of MHD. This method is suitable for pharmacokinetic study in small animals.
奥卡西平（OXC）是一种第二代抗癫痫药物，在体内会迅速还原并生成活性代谢物10,11-二氢-10-羟基卡马西平（MHD）。在本研究中，开发并验证了一种使用超高效液相色谱-串联质谱法（UPLC-MS-MS）同时测定大鼠血浆中OXC和MHD的方法。在给定的色谱条件下，OXC、MHD和内标地西泮分离良好，并通过电喷雾正离子质谱在多反应监测过渡模式下进行定量。方法验证表明，OXC在10 - 2000 ng/mL范围内、MHD在5 - 1000 ng/mL范围内具有良好的线性。OXC和MHD的定量下限分别为5 ng/mL和2.5 ng/mL。该方法成功应用于评估OXC和MHD在大鼠体内的药代动力学，无论大鼠是否经酮康唑（KET）和伏立康唑（VOR）预处理。统计表明，KET和VOR显著影响OXC和MHD在体内的处置，而VOR主要干扰MHD的处置。该方法适用于小动物的药代动力学研究。
