Simple quantification of propofol and its metabolites in blood and urine using gas chromatography–tandem mass spectrometry (GC–MS/MS)

Abstract

An analytical method which was used for the simultaneous detection and quantification of propofol and its metabolites in human blood and urine by gas chromatography-tandem mass spectrometry (GC–MS/MS) was newly established and applied to authentic human samples obtained from the deceased. The QuEChERS method was employed, and then analyzed by GC–MS/MS. We separately used sulfatase and β-glucuronidase to hydrolyze the urine sample and calculated the increase of propofol and 4-hydroxypropofol before and after the hydrolysis. The results of urinary concentrations in urine from the subject were: 4.88 μg/mL for propofol, 0.53 μg/mL for 4-hydroxypropofol, 3.35 μg/mL for propofol-glucuronide, 0.31 μg/mL for the total concentration of 1-(2,6-diisopropyl-1,4-quinol)-glucuronide plus 4-(2,6-diisopropyl-1,4-quinol)-glucuronide, and 0.39 μg/mL for 4-(2,6- diisopropyl-1,4-quinol)-sulfate. The lower limit of quantification was 10 ng/mL for all determined compounds; the extraction recoveries were not less than 57.2 %. Intraday and interday precisions and accuracies were all less than 10 %. The calibration curves for propofol and 4-hydroxypropofol in human urine showed the correlation values of not less than 0.999; propofol and 4-hydroxypropofol in blood also presented good linearities in the concentration ranges of 0.1–10 μg/mL. The two compounds had good stability within 7 days at 25, 4, and −20 ℃. To our knowledge, this is the first trial to establish a simple and reliable method to simultaneously detect and quantify of propofol and its phase I and II metabolites in human blood and urine samples by GC–MS/MS.