P2 The detection of propofol glucuronide in human hair using LC-MS/MS: Case study and survey of high-risk health professionals

Abstract

Background Propofol (2,6-diisopropylphenol) is a commonly used agent for general anesthesia because of its short duration, quick recovery time, and minimal side effects. Although not a controlled substance in the United States, propofol abuse and misuse by medical professionals has increased 5-fold between 1997 and 2011. Propofol detection in biological fluids has a very short detection window and the presence of propofol in hair does not distinguish between ingestion and environmental exposure. A metabolite, propofol glucuronide, is formed in the liver and may be detected in the hair. The purpose of this study is to validate a method for the detection of propofol glucuronide in hair and apply this method to a case study and a survey of high-risk health professionals. Methods A method for the detection of propofol glucuronide was developed and validated according commonly recognized guidelines. Briefly, hair specimens were powdered and extracted into water while incubating in a sonicating water batch without heat over night. Extracts were subjected to solid phase extraction using quaternary amine with chloride counter ion extraction cartridges. The eluates were evaporated under nitrogen at 40 °C, reconstituted in 100 μL of DI water. Extracts were separated using Synergy Polar RP column (50mm x 2mm x 2.5 μm particle size) on an Agilent 1200 HPLC system. The compounds were detected on an AB Sciex 5500 tandem mass spectrometer (LC-MS/MS) following the transitions of 353,1 m/z to 176,7 m/z , 112,6 m/z , 84,7 m/z for propofol glucuronide and 370,1 m/z to 193,7 m/z and 369,7 m/z for the internal standard, propofol glucuronide- d 17 . A hair specimen that originated from a 50 year old woman that was anesthetized for 15 minutes was analyzed. Additionally, a survey of 300 de-identified hair specimen remnants that originated from health professionals undergoing treatment for substance abuse. Results The empirically determined LOD and LOQ for this assay were 4 pg/mg and 8 pg/mg, respectively. The intra- and inter-assay bias and imprecision studies were all acceptable ( Conclusion This method demonstrated sufficient precision, accuracy and robustness with an analytical measurement range between 8 pg/mg and 100 pg/mg. While being sensitive enough to identify two individuals in a survey of high-risk substance abuse treatment participants, the method was not able to identify propofol metabolite in the hair of a woman receiving a routine quantity of propofol administered during a short surgical procedure. This method provides substance abuse treatment professionals with another objective tool to identify propofol abusers.