Deng Pan, Zhong Dafang, Chen Xiaoyan
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 646 Songtao Road, Shanghai 201203, China.
J Pharm Biomed Anal. 2009 Apr 5;49(3):848-52. doi: 10.1016/j.jpba.2008.12.038. Epub 2009 Jan 8.
A sensitive and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for the determination of tropisetron in human plasma was developed and validated over the concentration range of 0.100-100 ng/mL. Diphenhydramine was used as the internal standard (IS). The tropisetron and the IS were extracted from alkalized plasma samples into diethyl ether-dichloromethane (2:1, v/v) and the LC separation was performed by a Diamonsil C18 column (150 mm x 4.6 mm, i.d., 5 microm). The mobile phase was methanol:water (80:20, v/v) containing 0.2% formic acid delivered at a flow rate of 0.5 mL/min. The total chromatographic run time was 4.5 min. The MS data acquisition was accomplished by selected reaction monitoring (SRM) mode with positive atmospheric pressure chemical ionization (APCI) interface. The lower limit of quantification (LLOQ) achieved was 0.100 ng/mL with precision (RSD) of 3.1% and accuracy (RE) of -0.7%. For both inter-batch and intra-batch tests, the precision (RSD) for the entire validation was less than 6.0%, and the accuracy (RE) was within the -0.5% to 0.2% range. This validated LC-MS/MS method was later used to characterize the pharmacokinetics as well as the bioequivalence of tropisetron formulations.
建立了一种灵敏且具选择性的液相色谱 - 串联质谱法（LC - MS/MS）用于测定人血浆中的托烷司琼，并在0.100 - 100 ng/mL浓度范围内进行了验证。以苯海拉明作为内标（IS）。将托烷司琼和内标从碱化的血浆样品中萃取至乙醚 - 二氯甲烷（2:1，v/v）中，采用Diamonsil C18柱（150 mm×4.6 mm，内径，5 μm）进行LC分离。流动相为含0.2%甲酸的甲醇:水（80:20，v/v），流速为0.5 mL/min。总色谱运行时间为4.5 min。通过选择反应监测（SRM）模式和正大气压化学电离（APCI）接口完成MS数据采集。获得的定量下限（LLOQ）为0.100 ng/mL，精密度（RSD）为3.1%，准确度（RE）为 - 0.7%。对于批间和批内试验，整个验证过程中的精密度（RSD）均小于6.0%，准确度（RE）在 - 0.5%至0.2%范围内。该经验证的LC - MS/MS方法随后用于表征托烷司琼制剂的药代动力学及生物等效性。
