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

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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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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS), KAKENHI grant (C) 24590865.

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Authors and Affiliations

  1. Department of Legal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Yuki Kaki, Masaya Fujishiro, Xiao-Pen Lee, Mari Hashimoto, Sawa Minohara, Chika Hasegawa, Takeshi Kumazawa, Keizo Sato & Takaaki Matsuyama

  2. Department of Emergency and Disaster Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Yuki Kaki, Akihito Kato & Kenji Dohi

  3. Shimadzu Corporation, Nakagyo-ku, Kyoto, 604-8511, Japan

    Yuki Sakamoto

  4. Department of Legal Medicine, Toho University School of Medicine, Ota-ku, Tokyo, 143-8540, Japan

    Chika Hasegawa

  5. University Center of Legal Medicine, Kanagawa Dental University, Yokosuka-shi, Kanagawa, 238-8580, Japan

    Iwao Hasegawa

  6. Seirei Christopher University School of Nursing, Hamamatsu, Shizuoka, 433-8558, Japan

    Takeshi Kumazawa

  7. Department of Legal Medicine and Bioethics, Nagoya University, Showa-ku, Nagoya, 466-8550, Japan

    Akira Ishii

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  1. Yuki Kaki
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  2. Masaya Fujishiro
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Corresponding author

Correspondence to Xiao-Pen Lee.

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The authors declare no conflict of interest associated with this manuscript.

Ethical approval

This study was approved by the Ethics Committee of Showa University School of Medicine, and informed consent was obtained from the family of the patient prior to participation in this study (No. 2715). The collection of blank blood samples from healthy volunteers was approved by the Ethics Committees of Showa University School of Medicine (No. 1249).

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Kaki, Y., Fujishiro, M., Lee, XP. et al. Sensitive determination of midazolam and propofol in human plasma by GC–MS/MS. Forensic Toxicol 38, 409–419 (2020). https://doi.org/10.1007/s11419-020-00529-8

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  • DOI: https://doi.org/10.1007/s11419-020-00529-8

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