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用于临床药代动力学研究的人血浆中乙胺嗪的液相色谱-质谱分析。

Liquid chromatography-mass spectrometry analysis of diethylcarbamazine in human plasma for clinical pharmacokinetic studies.

作者信息

Schmidt Mark S, King Christopher L, Thomsen Edward K, Siba Peter M, Sanuku Nelly, Fleckenstein Lawrence

机构信息

College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.

School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.

出版信息

J Pharm Biomed Anal. 2014 Sep;98:307-10. doi: 10.1016/j.jpba.2014.05.016. Epub 2014 May 22.

DOI:10.1016/j.jpba.2014.05.016
PMID:24975211
Abstract

A sensitive and selective liquid chromatographic method using mass spectrometric detection was developed for the determination of diethylcarbamazine (DEC) in human plasma. DEC and its stable isotope internal standard d3-DEC were extracted from 0.25mL of human plasma using solid phase extraction. Chromatography was performed using a Phenomenex Synergi 4μ Fusion-RP column (2mm×250mm) with gradient elution. The retention time was approximately 4.8min. The assay was linear from 4 to 2200ng/mL. Analysis of quality control samples at 12, 300, and 1700ng/mL (N=15) had interday coefficients of variation of 8.4%, 5.4%, and 6.2%, respectively (N=15). Interday bias results were -2.2%, 6.0%, and 0.8%, respectively. Recovery of DEC from plasma ranged from 84.2% to 90.1%. The method was successfully applied to clinical samples from patients with lymphatic filariasis from a drug-drug interaction study between DEC and albendazole and/or ivermectin.

摘要

建立了一种采用质谱检测的灵敏且选择性好的液相色谱法,用于测定人血浆中的乙胺嗪(DEC)。使用固相萃取法从0.25mL人血浆中提取DEC及其稳定同位素内标d3-DEC。采用Phenomenex Synergi 4μ Fusion-RP柱(2mm×250mm)进行梯度洗脱色谱分析。保留时间约为4.8分钟。该测定法在4至2200ng/mL范围内呈线性。对浓度为12、300和1700ng/mL的质量控制样品进行分析(N = 15),日间变异系数分别为8.4%、5.4%和6.2%(N = 15)。日间偏差结果分别为-2.2%、6.0%和0.8%。血浆中DEC的回收率在84.2%至90.1%之间。该方法成功应用于来自淋巴丝虫病患者的临床样品,用于DEC与阿苯达唑和/或伊维菌素之间的药物相互作用研究。

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引用本文的文献

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LC-MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma: Application to a clinical pharmacokinetic study.LC-MS/MS 法同时测定人血浆中的乙胺嗪、阿苯达唑及其代谢物:在临床药代动力学研究中的应用。
J Pharm Biomed Anal. 2018 Mar 20;151:84-90. doi: 10.1016/j.jpba.2017.12.037. Epub 2017 Dec 24.