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Published in: Forensic Toxicology 2/2020

01-07-2020 | Midazolam | Original Article

Sensitive determination of midazolam and propofol in human plasma by GC–MS/MS

Authors: Yuki Kaki, Masaya Fujishiro, Xiao-Pen Lee, Akihito Kato, Yuki Sakamoto, Mari Hashimoto, Sawa Minohara, Chika Hasegawa, Iwao Hasegawa, Kenji Dohi, Takeshi Kumazawa, Akira Ishii, Keizo Sato, Takaaki Matsuyama

Published in: Forensic Toxicology | Issue 2/2020

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Abstract

Purpose

A sensitive method was developed for the simultaneous determination of midazolam and propofol in human plasma samples via modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction for their analysis by gas chromatography–tandem mass spectrometry (GC–MS/MS).

Methods

Detailed optimization and validation experiments were conducted; plasma quality control samples spiked with two drugs and two internal standards (ISs) were extracted using the QuEChERS technique and determined by GC–MS/MS. The present method was applied to the measurements in an actual clinical case.

Results

The regression equations for midazolam and propofol in plasma displayed good linearity (r > 0.9978) from 10 to 1000 ng/mL with a limit of quantification of 10 ng/mL. The intra- and interday precisions for both drugs were not greater than 8.6%. The accuracies of quantitation ranged from 98 to 110%. The extraction efficiencies of midazolam and propofol for plasma were 93 to 117%. The method was successfully applied to the analyses of plasma midazolam and propofol concentrations in a brain-injured patient subjected to hypothermia, which validated the present methodology.

Conclusions

In this study, the authors have successfully established the detailed procedure for GC–MS/MS analysis of midazolam and propofol in human plasma. The sensitivity and specificity of the present method for the drugs were almost comparable to those by the standard liquid chromatography–tandem mass spectrometry. To their knowledge, this is the first report for analysis of midazolam/propofol by GC–MS/MS.
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Metadata
Title
Sensitive determination of midazolam and propofol in human plasma by GC–MS/MS
Authors
Yuki Kaki
Masaya Fujishiro
Xiao-Pen Lee
Akihito Kato
Yuki Sakamoto
Mari Hashimoto
Sawa Minohara
Chika Hasegawa
Iwao Hasegawa
Kenji Dohi
Takeshi Kumazawa
Akira Ishii
Keizo Sato
Takaaki Matsuyama
Publication date
01-07-2020
Publisher
Springer Singapore
Published in
Forensic Toxicology / Issue 2/2020
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-020-00529-8

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