1,2-Dimethylimidazole-4-sulfonyl chloride (DMISC), a novel derivatization strategy for the analysis of propofol by LC-ESI-MS/MS.

Abstract

Analysis of the anesthetic agent propofol in biological samples by LC-MS/MS is a great challenge due to weak fragmentation and poor ionization efficacy of propofol resulting in weak signal intensities. Improvements of the ionization and fragmentation efficacy can be achieved by conversion of propofol to its dimethylimidazolesulfonyl (DMIS) derivative by a derivatization reaction using 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC). This DMIS derivative produced intense [M + H]+ ions in positive-ion LC-ESI-MS/MS with the dimethylimidazole moieties representing the most abundant product ions. Derivatization of serum samples is achieved by direct conversion of the acetonitrile supernatant of a protein precipitation with DMISC followed by a double liquid-liquid extraction using n-hexane. Reliability of the method was confirmed under consideration of the validation parameters selectivity, linearity, accuracy and precision, analytical limits, and processed sample stability. Linearity was demonstrated over the whole calibration range from 5 to 1000ng/ml with the use of a 1/x 2 weighting. Stability of the processed samples was verified for a time period of up to 25h. Due to its high sensitivity, appropriate quantification and detection limits (LLoQ = 5ng/ml, LoD = 0.95ng/ml) for toxicological propofol analyses could be achieved. Applicability of the method to biological samples could be verified by analysis of a human serum sample collected after propofol-induced sedation. Graphical abstract A novel derivatization strategy using 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC) was developed to improve the ionization and fragmentation efficacy of propofol for LC-ESI-MS/MS analysis.