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LC-MS/MS analysis of propofol in postmortem blood: propofol glucuronide as an indicator of exposure
Koji Yamaguchi1, Ayumi Motomura1, Namiko Ishii1
1Department of Forensic Medicine, Faculty of Medicine, International University of Health and Welfare, 4-3 Kouzunomori, Narita, 286-8686, Japan.
Abstract:
Propofol (PRF) is a short-acting intravenous anesthetic widely used for the induction and maintenance of general anesthesia. However, multiple accidental deaths resulting from the non-therapeutic use of PRF have been reported; therefore, PRF is an important target analyte in forensic investigations. In this study, quantitative analytical methods for PRF and propofol glucuronide (PRG) in postmortem blood were developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For quantification, PRF was derivatized with N-(2-(bromomethyl)benzyl)-N,N-diethylethanaminium bromide (CAXB) to increase LC-MS/MS detection sensitivity. PRF was quantified using selected reaction monitoring (SRM) in positive ion mode. The extract was diluted after the derivatization reaction, and the quantification range was set to 0.1-20 μg/mL, which is suitable for routine quantitative analysis of PRF in postmortem blood samples. PRG was quantified using SRM in positive ion mode. Both analytical methods were validated and applied to authentic postmortem blood samples. The utility of PRG as a complementary marker in SRM-based drug screening was evaluated. Our findings demonstrate that PRG is a valuable indicator of PRF exposure in forensic casework and may help address limitations in the routine detection of PRF.
Insights
This study developed new methods to detect propofol (PRF) and its metabolite propofol glucuronide (PRG) in postmortem blood. PRG is a valuable indicator of PRF exposure in forensic investigations.
Area of Science:
- Forensic Toxicology
- Analytical Chemistry
- Pharmacology
Background:
- Propofol (PRF) is a widely used anesthetic with reported non-therapeutic deaths.
- PRF is a crucial analyte in forensic investigations due to its abuse potential.
- Accurate quantification of PRF and its metabolites in postmortem samples is essential for forensic casework.
Purpose of the Study:
- To develop and validate quantitative analytical methods for propofol (PRF) and propofol glucuronide (PRG) in postmortem blood.
- To evaluate the utility of PRG as a complementary marker for PRF exposure in forensic toxicology.
- To improve the detection capabilities for PRF in postmortem investigations.
Main Methods:
- Development of quantitative methods using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Derivatization of PRF with N-(2-(bromomethyl)benzyl)-N,N-diethylethanaminium bromide (CAXB) for enhanced detection sensitivity.
- Quantification of PRF and PRG using selected reaction monitoring (SRM) in positive ion mode.
Main Results:
- Validated LC-MS/MS methods for PRF and PRG in postmortem blood.
- Established a quantification range of 0.1-20 μg/mL for PRF, suitable for routine analysis.
- Demonstrated that PRG is a valuable indicator of PRF exposure, complementing PRF detection.
Conclusions:
- The developed LC-MS/MS methods are effective for quantifying PRF and PRG in postmortem blood.
- Propofol glucuronide (PRG) serves as a valuable complementary marker for detecting propofol exposure in forensic casework.
- These findings enhance the capabilities for routine drug screening and forensic investigations involving propofol.
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