Rapid Evaluation Method for Propofol Abusing with Hair by Using Centrifugal Filter and Liquid Chromatography-tandem Mass Spectrometry

Abstract

Background: Since propofol is rapidly metabolized and excreted from the body, it is not easy to quantify its intake in blood or urine samples over the time. In this case, the hair sample would be more advantageous to estimate during the abuse period. However, the presence of protein and lipid in the hair sample could interfere with extraction and be problematic during mass spectrometric analysis. Objective: The aim of this study is to develop a simple and less time-consuming method for the extraction of propofol glucuronide by removing hair interferences with the centrifugal filter. Methods: Hair samples were washed and dissolved with sodium hydroxide solution. This dissolved hair solution was applied to the centrifugal filter and centrifuged. The filtrate was extracted with ethyl acetate and evaporated to dryness. The residue was reconstituted with methanol and analyzed by liquid chromatography coupled with tandem mass spectrometry. This developed analytical method was validated by testing linearity, selectivity, accuracy, precision, recovery, matrix effect and stability of propofol glucuronide. Results: The validation results showed good linearity over the concentration range of 0.5~500 pg/mg, with a correlation coefficient of 0.9991. The LOD and LLOQ were 0.2 and 0.5 pg/mg, respectively. The intra-and inter-day precision and accuracy were acceptable within 14.5% for precision and 10.1% for accuracy. Similarly, the developed method revealed high sample recovery (>88%), low hair matrix effect (<10%) and highly-efficient extraction procedure. Conclusion: This well-validated procedure was successfully applied to determine propofol glucuronide in a rat hair sample and can be applicable, with high potential, in the field of forensic toxicology especially with increasing abuse and accidental overdose of propofol.