Center for Advancement of Drug Research and Evaluation, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Jan 1;879(1):95-9. doi: 10.1016/j.jchromb.2010.11.022. Epub 2010 Dec 1.
Meclizine is an antihistamine and has been widely used for prophylactic treatment of motion sickness. To facilitate its pharmacokinetic study in human subjects, a high performance liquid chromatography-mass spectrometric method employing positive electrospray ionization was developed for the determination of meclizine concentration in human plasma.
Meclizine together with the internal standard (flunarizine) was extracted from 0.1 ml of human plasma by protein precipitation using acetonitrile. The chromatography was performed using a Zorbax SB-C18 column (150 × 2.1mm, 5 μm, Agilent) with the mobile phase consisting of acetonitrile and 0.2% formic acid containing 2mM amino acetate. Multiple reaction monitoring was used for quantification. The validation of the method including sensitivity, linearity, reproducibility and stability was examined.
The lower limit of quantification (LLOQ) of the developed assay method for meclizine was 0.5 ng/ml and the linear calibration curve was acquired with R² > 0.99 between 0.5 and 200ng/ml. The intra-day and inter-day variation of the current assay was evaluated with the coefficient of variations (CVs%) within 12.92% at LLOQ and 7.15% for other quality control samples, whereas the mean accuracy ranged from 99.2% to 102.7%. The samples were stable under the storage conditions at least for a month.
The present method provides a robust, fast and sensitive analytical tool for meclizine in human plasma and has been successfully applied to a clinical pharmacokinetic study in 20 subjects.
美克洛嗪是一种抗组胺药，已广泛用于预防晕动病。为了促进其在人体中的药代动力学研究，开发了一种采用正电喷雾电离的高效液相色谱-质谱联用法，用于测定人血浆中美克洛嗪的浓度。
美克洛嗪与内标（氟桂利嗪）一起，通过用乙腈沉淀蛋白质从 0.1ml 人血浆中提取。采用 Zorbax SB-C18 柱（150×2.1mm，5μm，Agilent）进行色谱分离，流动相由乙腈和含 2mM 氨基乙酸的 0.2%甲酸组成。采用多反应监测进行定量。对方法的验证包括灵敏度、线性、重现性和稳定性进行了考察。
该方法测定美克洛嗪的定量下限（LLOQ）为 0.5ng/ml，在 0.5 至 200ng/ml 范围内，线性校准曲线的 R²>0.99。当前测定方法的日内和日间变异用 LLOQ 时的变异系数（CVs%）在 12.92%以内和其他质控样品时的 7.15%来评估，而平均准确度范围为 99.2%至 102.7%。在至少一个月的储存条件下，样品稳定。
本方法提供了一种用于人血浆中美克洛嗪的强大、快速和灵敏的分析工具，并已成功应用于 20 名受试者的临床药代动力学研究。
