Tian Lei, Jiang Juanjuan, Huang Yiling, Hua Lu, Liu Hong, Li Yishi
Clinical Pharmacology Center, Fu Wai Hospital, CAMS and PUMC, 167 Beilishi Road, Beijing 100037, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Feb 1;846(1-2):346-50. doi: 10.1016/j.jchromb.2006.08.010. Epub 2006 Sep 7.
A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method with positive electrospray ionization (ESI) was developed for the quantification of ranolazine in human plasma. After liquid-liquid extraction of ranolazine and internal standard (ISTD) phenoprolamine from a 100 microl specimen of plasma, HPLC separation was achieved on a Nova-Pak C(18) column, using acetonitrile-water-formic acid-10% n-butylamine (70:30:0.5:0.08, v/v/v/v) as the mobile phase. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode using the transition m/z 428.5-->m/z 279.1 for ranolazine and m/z 344.3-->m/z 165.1 for the internal standard, respectively. Linear calibration curves were obtained in the concentration range of 5-4000 ng/ml, with a lower limit of quantitation (LLOQ) of 5 ng/ml. The intra- and inter-day precision values were below 3.7% and accuracy was within +/-3.2% at all three quality control (QC) levels. This method was found suitable for the analysis of plasma samples collected during the phase I pharmacokinetic studies of ranolazine performed in 28 healthy volunteers after single oral doses from 200 mg to 800 mg.
建立了一种采用正电喷雾电离（ESI）的快速、选择性和灵敏的液相色谱-串联质谱（LC-MS-MS）方法，用于定量测定人血浆中的雷诺嗪。从100微升血浆标本中液-液萃取雷诺嗪和内标（ISTD）非诺拉明后，在Nova-Pak C(18)柱上进行高效液相色谱分离，使用乙腈-水-甲酸-10%正丁胺（70:30:0.5:0.08，v/v/v/v）作为流动相。质谱仪在多反应监测（MRM）模式下运行，雷诺嗪的跃迁为m/z 428.5→m/z 279.1，内标的跃迁为m/z 344.3→m/z 165.1。在5-4000 ng/ml的浓度范围内获得线性校准曲线，定量下限（LLOQ）为5 ng/ml。在所有三个质量控制（QC）水平下，日内和日间精密度值均低于3.7%，准确度在±3.2%以内。该方法适用于分析28名健康志愿者单次口服200 mg至800 mg雷诺嗪后进行的I期药代动力学研究期间采集的血浆样本。
