A highly sensitive LC-MS-MS assay for analysis of midazolam and its major metabolite in human plasma: Applications to drug metabolism

被引：38

作者：

Jabor, VAP

Coelho, EB

dos Santos, NAG

Bonato, PS

Lanchote, VL ^{[1
]}

机构：

[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Sao Paulo, Brazil

[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, BR-14040903 Sao Paulo, Brazil

[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim & Fis, BR-14040903 Sao Paulo, Brazil

来源：

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2005年 / 822卷 / 1-2期

基金：

巴西圣保罗研究基金会;

关键词：

midazolam; LC-MS-MS; plasma; pharmacokinetics; CYP3A4;

D O I：

10.1016/j.jchromb.2005.05.011

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The present report describes a rapid, selective and a highly sensitive assay for midazolam (MDZ) and its major metabolite I-hydroxymidazolarn (l-OH-MDZ) in human plasma employing liquid chromatography-tandem mass spectrometry (LC-MS-MS) detection. The method involves liquid-liquid extraction sample clean-up, separation on a Purospher RP 18-e column and detection with an electrospray interface in the positive ion mode. The overall recoveries were about 100% and 80% for midazolam and 1-hydroxymidazolam, respectively. Accuracy, precision and linearity were acceptable for biological samples with quantitation limits of 0.1-100ngmL(-1) plasma for both analytes. The validated method was successfully applied to quantify plasma concentration of midazolam and 1-hydroxymidazolam in authentic samples from a healthy volunteer following a single 15 mg oral dose of midazolam (apparent total clearance: 3.47 L h(-1) kg(-1) and AUC(0-alpha)IOH-MDZ/MDZ: 0.338). (c) 2005 Elsevier B.V. All rights reserved.

引用

页码：27 / 32

页数：6

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