Analysis of midazolam and metabolites in plasma by high-performance liquid chromatography: Probe of CYP3A

被引：70

作者：

Carrillo, JA ^{[1
]}

Ramos, SI ^{[1
]}

Agundez, JAG ^{[1
]}

Martinez, C ^{[1
]}

Benitez, J ^{[1
]}

机构：

[1] Univ Extremadura, Fac Med, Dept Farmacol & Psiquiatria, E-06071 Badajoz, Spain

来源：

THERAPEUTIC DRUG MONITORING | 1998年 / 20卷 / 03期

关键词：

midazolam; metabolites; high-performance liquid chromatography; CYP3A;

D O I：

10.1097/00007691-199806000-00013

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

Hydroxylation of midazolam (MDZ) is mediated almost exclusively by CYP3A isoforms. The authors describe a high-performance liquid chromatography assay involving MDZ, 1'-hydroxymidazolam, and 4-hydroxymidazolam in plasma. The compounds were eluted on an Ultrasphere ODS, 3-mu m particle size, 7.5 cm x 4.6 mm reversed-phase column and monitored by ultraviolet absorbance at 254 nm. The composition of the mobile phase was 35.2% acetonitrile:4.8% methanol:60% buffer acetate (vol/vol/vol), 0.1 M, pH 4.7; the flow rate was 1 ml/minute. Calibration curves were linear (coefficients of correlation >0.99) within the range of concentrations established (20 to 640 nM). Within- and between-day coefficients of variation were consistently better than 8%. The overall recovery was >90% and the lowest detectable concentration was 8 nM. This approach provides a simple, rapid, and sensitive assessment of MDZ and metabolites in plasma, with a very good accuracy and precision, which enables it as an in vivo marker of CYP3A activity in humans.

引用

页码：319 / 324

页数：6

共 25 条

[1] Rifampin drastically reduces plasma concentrations and effects of oral midazolam [J].