LC-MS/MS法测定人血浆中加巴喷丁的浓度及其药动学研究  

LC-MS/MS method for quantification and pharmacokinetic study of gabapentin in human plasma

作　　者：熊志立[1] 俞嘉[1] 何积芬[1] 秦峰[1] 李发美[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《药学学报》2011年第10期1246-1250,共5页Acta Pharmaceutica Sinica

基　　金：重大新药创新综合平台临床前药物代谢动力学技术与平台项目(2009ZX09301-012)

摘　　要：建立液相色谱串联质谱(LC-MS/MS)法测定人血浆中加巴喷丁的浓度并将其应用于人体药动学研究。取血浆样品经甲醇沉淀蛋白后,以甲醇0.2%甲酸水溶液(80∶20)为流动相,用Inertsil ODS-3 C18柱(50 mm×2.1 mm ID,3μm)分离,采用电喷雾离子源,以多反应监测(MRM)方式进行正离子检测,定量分析的离子反应分别为m/z 172→m/z 154(加巴喷丁)和m/z 130→m/z 71(内标二甲双胍)。加巴喷丁线性范围为40.8～8.16×103 ng.mL 1,定量限为40.8 ng.mL 1,每个样品测试时间仅2.2 min,日内、日间精密度(RSD)均小于12%,准确度(RE)在±6.4%范围内。应用此法研究了20名健康志愿者单剂量口服加巴喷丁胶囊600 mg后的药动学特点。该方法快速、专属、灵敏、适用性强,可应用于加巴喷丁的人体药动学研究。A sensitive,rapid and specific liquid chromatographic-tandem mass spectrometric（LC-MS/MS） method for quantification of gabapentin in human plasma has been developed.After a single plasma protein precipitation with methanol,gabapentin and metformin（internal standard） were chromatographed on a Inertsil ODS-3 column（50 mm × 2.1 mm ID,3 μm） with mobile phase consisting of methanol 0.2% formic acid aqueous solution（80∶20,v/v） at a flow-rate of 0.2 mL min 1.Electrospray ionization（ESI） source was applied and operated in the positive ion mode.Multiple reaction monitoring（MRM） mode with the transitions of m/z 172 → m/z 154 and m/z 130 → m/z 71 were used to quantify gabapentin and metformin,respectively.The run time was 2.2 min.The linear calibration curve was obtained in the concentration range of 40.8 8.16×103 ng mL 1.The lower limit of quantification was 40.8 ng mL 1.The intra-and inter-day precision（RSD） was less than 12%,and the accuracy（RE） was within ±6.4% calculated from quality control（QC） samples.The method was used to determine the concentration of gabapentin in human plasma after a single oral administration of 600 mg gabapentin capsule to 20 healthy male Chinese volunteers.The method was proved to be selective,sensitive,rapid and suitable for pharmacokinetic study of gabapentin in human plasma.

关 键 词：加巴喷丁 液相色谱串联质谱法 药动学研究 

分 类 号：R969[医药卫生—药理学]