同时测定人血浆中4种国产与进口抗癫痫药浓度的超高效液相色谱-质谱联用法的建立  

Simultaneous determination of four kinds of domestic and imported anti-epilepsy drugs in human plasma by UPLC-MS /MS

作　　者：王伟[1] 刘永锁[1] 乔湜[1] 李清艳[1] 

机构地区：[1]民用航空医学中心(民航总医院)航空医学研究所,北京100123

出　　处：《中国临床药理学杂志》2014年第9期807-809,815,共4页The Chinese Journal of Clinical Pharmacology

基　　金：民航总医院院级课题基金资助项目(2012018);民航科技基金资助项目(MHRD201235)

摘　　要：目的 建立同时测定人血浆中苯巴比妥、苯妥英钠、托吡酯及左乙拉西坦浓度的方法。方法 以磺胺甲噁唑（SMZ）和吡格列酮为内标,血浆经甲醇直接沉淀后进样分析。色谱柱为ACQUITY UPLC HSS PFP柱,流动相为含0.1%甲酸的5 mmol·L^-1乙酸铵水溶液-甲醇溶液,流速为0.2 mL·min^-1,电喷雾离子源,用多反应监测,结合正负离子分段扫描分析。结果 苯巴比妥、苯妥英钠、托吡酯及左乙拉西坦血药浓度分别在1.15-230.00（r=0.997 3）,0.10-20.20（r=0.998 5）,0.02-2.12（r=0.996 5）,0.10-20.40μg·mL^-1（r=0.996 3）内线性关系良好。日内、日间精密度（RSD）均〈15%;提取回收率均〉75%。结论该方法灵敏、快速、专属性强,可用于临床血药浓度测定及药代动力学研究。Objective To develop the method for concentration determination of phenobarbital,phenytoin sodium,topiramate and levertiracetam in human plasma. Methods UPLC- MS /MS was adopted to analyze plasma with protein precipitated by methanol. Sulfamethlazole（ SMZ） and pioglitazone hydrochloride were as internal standard. Plasma samples were separated on ACQUITY UPLC HSS PFP column with aqueous solution（ 0.1% formic acid-5 mmol·L^- 1ammonium acetate buffer）- methanol as mobile phase,and at a flow rate of 0. 2 mL·min^- 1. Multiple reaction monitoring（ MRM） mode was performed combined with the ion switching technology for quantification in three sections. Results The liner calibration curve of phenobarbital,phenytoin sodium,topiramate and levertiracetam were obtained in the concentration range of 1. 15- 230. 00（ r =0. 997 3）,0. 10- 20. 20（ r = 0. 998 5）,0. 02- 2. 12（ r = 0. 996 5） and0. 10- 20. 40 μg·mL^- 1（ r =0.996 3）,respectively. The lowest detection limit were 230. 0,20. 20,5. 30,20. 40 ng·mL- 1,respectively. The RSD of inter- day and intra- day were less than 15%. The relative recovery was more than 75%. Conclusion The method is accurate,sensitive and suitable for blood concentration monitoring and pharmacokinetic study of phenobarbital,phenytoin sodium,topiramate and levertiracetam.

关 键 词：苯巴比妥 苯妥英钠 托吡酯 左乙拉西坦 超高效液相色谱法-质谱联用法 

分 类 号：R971.6[医药卫生—药品] R969.1[医药卫生—药学]