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

• Published in: Forensic toxicology 2020-07, Vol.38 (2), p.409-419
• Main Authors: Kaki, Yuki, Fujishiro, Masaya, Lee, Xiao-Pen, Kato, Akihito, Sakamoto, Yuki, Hashimoto, Mari, Minohara, Sawa, Hasegawa, Chika, Hasegawa, Iwao, Dohi, Kenji, Kumazawa, Takeshi, Ishii, Akira, Sato, Keizo, Matsuyama, Takaaki
• Format: Article
• Language: English
• Subjects: Forensic Medicine; Forensic Science; Medical Law; Medicinal Chemistry; Medicine; Medicine & Public Health; Original Article; Pharmacology/Toxicology
• ISSN: 1860-8965; 1860-8973
• DOI: 10.1007/s11419-020-00529-8

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.