Determination of midazolam in human plasma by solid‐phase microextraction and gas chromatography/mass spectrometry

Abstract

A new method is described for the qualitative and quantitative analysis of midazolam, a short-acting 1,4-imidazole benzodiazepine, in human plasma. It involves a plasma deproteinization step, solid-phase microextraction (SPME) of midazolam using an 85-microm polyacrylate fiber, and its detection by gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring (SIM) mode, using pinazepam as internal standard. The assay is linear over a midazolam plasma range of 1.5-300 ng/mL, relative intra- and inter-assay standard deviations at 5 ng/mL are below 7%, and the limit of detection is 1 ng/mL. The method is simple, fast and sufficiently sensitive to be applied in clinical and forensic toxicology as well as for purposes of therapeutic drug monitoring.

Determination of midazolam and its major metabolite 1′-hydroxymidazolam by high-performance liquid chromatography-electrospray mass spectrometry in plasma from children

“…Previously published GC-MS [30,31,38] and LC-MS [29,32,[35][36][37] techniques gave a lower limit of detection than the present technique (< 2 ng/ml). However, our LC-ESI-MS method is considerably more sensitive than most of the HPLC assays [16,18,20,23,29].…”

Determination of midazolam and 1-hydroxymidazolam from plasma by gas chromatography coupled to methane negative chemical ionization mass spectrometry after sublingual administration of midazolam

“…In addition, small amounts of inactive metabolites, 4-hydroxymidazolam (3%) and 1,4-dihydroxymidazolam (1%) are formed [11,12]. These phase I metabolites are further conjugated with glucuronic acid to form glucuronides as phase II metabolites [13].…”

Determination of 14 benzodiazepines and hydroxy metabolites, zaleplon and zolpidem as tert-butyldimethylsilyl derivatives compared with other common silylating reagents in whole blood by gas chromatography–mass spectrometry

“…Giroud et al used the same analytical technique for the simultaneous quantitative analysis of zolpidem and zaleplon, but did not include benzodiazepines [12]. Recent quantitative methodology for the analysis of benzodiazepines in serum, plasma or whole blood includes dual-column GC [13], GC-MS [14][15][16][17], GC-tandem mass spectrometry (GC-MS/MS) [18,19], liquid chromatography (LC) [20,21], liquid chromatography-mass spectrometry (LC-MS) [22][23][24][25][26] and liquid chromatography-tandem mass spectrometry (LC-MS/MS) [27][28][29][30]. However, GC-MS based techniques remain a method of choice for many routine laboratories due to the separation efficiency, versatility, ease of operation and maintenance, as well as lower costs of the analyses and investment expenses of an analytical system compared to LC-MS/MS.…”