Zhang Lu, Tian Yuan, Zhang Zunjian, Chen Yun
Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jul 1;854(1-2):91-8. doi: 10.1016/j.jchromb.2007.04.002. Epub 2007 Apr 8.
A selective and sensitive high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (ESI-MS/MS) method for simultaneous determination of metformin and rosiglitazone in human plasma using phenformin as internal standard (IS) has been first developed and validated. Plasma samples were precipitated by acetonitrile and the analytes were separated on a prepacked Phenomenex Luna 5u CN 100A (150 mm x 2.0 mm I.D.) column using a mobile phase comprised of methanol:30 mM ammonium acetate pH 5.0 (80:20, v/v) delivered at 0.2 ml/min. Detection was performed on a Finnigan TSQ triple-quadrupole tandem mass spectrometer in positive ion selected reaction monitoring (SRM) mode using electrospray ionization. The ion transitions monitored were m/z 130.27-->71.11 for metformin, m/z 358.14-->135.07 for rosiglitazone and m/z 206.20-->105.19 for the IS. The standard curves were linear (r(2)>0.99) over the concentration range of 5-3000 ng/ml for metformin and 1.5-500 ng/ml for rosiglitazone with acceptable accuracy and precision, respectively. The within- and between-batch precisions were less than 15% of the relative standard deviation. The limit of detection (LOD) of both metformin and rosiglitazone was 1 ng/ml. The method described is precise and sensitive and has been successfully applied to the study of pharmacokinetics of compound metformin and rosiglitazone capsules in 12 healthy Chinese volunteers.
首次建立并验证了一种选择性灵敏的高效液相色谱 - 电喷雾电离 - 串联质谱（ESI - MS/MS）方法，以苯乙双胍作为内标（IS）同时测定人血浆中的二甲双胍和罗格列酮。血浆样品用乙腈沉淀，分析物在预填充的Phenomenex Luna 5u CN 100A（150 mm×2.0 mm内径）柱上分离，流动相为甲醇：30 mM醋酸铵pH 5.0（80:20，v/v），流速为0.2 ml/min。在Finnigan TSQ三重四极杆串联质谱仪上采用电喷雾电离在正离子选择反应监测（SRM）模式下进行检测。监测的离子跃迁为二甲双胍的m/z 130.27→71.11，罗格列酮的m/z 358.14→135.07和内标的m/z 206.20→105.19。二甲双胍在5 - 3000 ng/ml浓度范围内、罗格列酮在1.5 - 500 ng/ml浓度范围内标准曲线呈线性（r(2)>0.99），准确度和精密度均可接受。批内和批间精密度均小于相对标准偏差的15%。二甲双胍和罗格列酮的检测限（LOD）均为1 ng/ml。所述方法准确灵敏，已成功应用于12名健康中国志愿者中复方二甲双胍和罗格列酮胶囊的药代动力学研究。
