HPLC-UV法同时测定卡马西平及其主要代谢物的血药浓度  

Determination of carbamazepine and its major metabolites in human serum by HPLC-UV

作　　者：朱旭[1] 刘美[1] 刘立民[1] 李新林[1] 孙亚欣[1] 肇丽梅[1] 

机构地区：[1]中国医科大学附属盛京医院药学部,沈阳110004

出　　处：《中国临床药理学杂志》2013年第11期853-856,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(30973597);辽宁省科学技术计划基金资助项目(2009225020)

摘　　要：目的建立同时测定卡马西平及其主要代谢物体内血药浓度的HPLC—UV法。方法以氯唑沙宗为内标，血样经乙醚-二氯甲烷（1：2）提取，流动相为甲醇-水（47：53），色谱柱为ZORBAX Plus C18（4．6mm×150mm，5μm），流速为1．0mL·min^-1，柱温为30℃，检测波长为215nm。结果卡马西平（CBZ）、10，11-环氧卡马西平（CBZE）和10，11-二羟基卡马西平（CBZ—diol）的线性范围分别为0．5—20．0，0．05—5．00和0．05—5．00μg·mL^-1，定量下限分别为0．50，0．05和0．05μg·mL^-1。CBZ，CBZE，CBZ—diol的低、中、高浓度回收率均约在80％，66％，60％，其日内、日间相对标准差均在±15％。210名单用CBZ患者体内CBZ，CBZE和CBZ—diol浓度范围分别为2．12～11．06，0．11～3．35和0．12～7．05μg·mL^-1；CBZ标准化血药浓度范围为0．17～2．26μg·kg·mL^-1·mg^-1。结论本方法稳定、快速、灵敏度高，专属性强，可用于常规治疗药物监测及卡马西平体内代谢研究。Objective To establish a HPLC -UV method for the determination of carbamazepine （CBZ） and its major metabolites in human serum. Methods Chlorzoxazone was internal standard. The serum samples were extracted with diethylether - dichloromethane （ 2 ： 1 ）. The analysis was conducted on an ZORBAX Plus Cls column. The flow rate was 1.0 mL · min^-1 and the column temperature was 30 ℃. The detecting wavelength was 215 nm. The mobile phase was methanol - water （47：53 ）. Results The linear ranges of CBZ, carbamazepine - 10, 11 - epoxide （CBZE） and dihydrocarbamazepine - 10, 11 - trans - diol （CBZ-diol） were 0.5-20.0, 0.05 -5.00 and 0.05 -5.00 μg·mL^-1. The lower limitation of quantification of CBZ, CBZE and CBZ - diol were 0. 50, 0. 05 and 0. 05μg·mL^-1, respectively. The recoveries of them were about 80%, 66% and 60%. The intra - and inter - day precision were all within ：1： 15%. The concentration ranges of CBZ, CBZE and CBZ -diol of 210 epileptic patients in carbamazepine mono- therapy were 2. 12 -11.06, 0. 11 -3.35 and 0. 12 -7.05μg·mL^-1, respectively. The standardized concentration rang of CBZ （ CDRCBZ） was 0. 17 -2. 26 μg·kg·mL^-1·mg^-1. Conclusion The method is stable, rapid, accurate, sensitive and specific. It is suitable for the studyon therapeutic drug monitoring and CBZ metabolism.

关 键 词：高效液相色谱-紫外法 血药浓度 卡马西平 10 11-环氧卡马西平 10 11-二羟基卡马西平 

分 类 号：R969.1[医药卫生—药理学] R971.41[医药卫生—药学]