Determination of the Long‐Term Stability of Propofol in Human Plasma Frozen for Eight Years and Quantified by UHPLC–MS/MS

The intravenous anesthetic propofol is frequently used for the induction and maintenance of general anesthesia. Propofol has, however, a potential for abuse, and it has been involved in suicide deaths particularly among medical personnel. The long‐term stability of propofol concentrations in human plasma samples when stored under normal laboratory conditions over several years might be important for forensic toxicology. The present study investigated the long‐term stability of propofol after storage at −20°C for eight years. For this purpose, 67 plasma samples from five patients, who had undergone a former clinical trial, were re‐analyzed. Plasma samples were extracted using protein precipitation. Propofol plasma concentrations were determined by ultra‐performance liquid chromatography (UPLC) with gradient elution, followed by tandem mass spectrometry with electrospray ionization. Deuterium‐labeled propofol was used as an internal standard. The assay was linear in the range of 50–10,000 ng/mL with a limit of detection of 0.5 ng/mL and a lower limit of quantification of 50 ng/mL, respectively. Accuracy and precision were high with intra‐ and interassay errors within ±5%. The median relative deviation between the measurements in 2023 and 2015 was −7.0% (interquartile range: −19.7% and 5.3%). Therefore, propofol concentrations in human plasma can be considered relatively stable in samples frozen at −20°C over eight years, and plasma samples stored under these conditions might be used for forensic purposes. Trial Registration: ClinicalTrials.gov identifier: NCT02199067