title: 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 1000 ng/ml with the use of a 1/x2weighting. Stability of the processed samples was verified for a time period of up to 25 h. Due to its high sensitivity, appropriate quantification and detection limits (LLoQ = 5 ng/ml, LoD = 0.95 ng/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.
authors.affiliation: Institute of Forensic Medicine, Department of Forensic Toxicology, University Bonn, Stiftsplatz 12, 53111, Bonn, Germany. alexandramaas@uni-bonn.de.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Maas
authors.affiliation: Department of Pain Management, BG University Hospital Bergmannsheil GmbH, Ruhr University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Maier
authors.affiliation: Department of Pain Management, BG University Hospital Bergmannsheil GmbH, Ruhr University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Michel-Lauter
authors.affiliation: Institute of Forensic Medicine, Department of Forensic Toxicology, University Bonn, Stiftsplatz 12, 53111, Bonn, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Madea
authors.affiliation: Institute of Forensic Medicine, Department of Forensic Toxicology, University Bonn, Stiftsplatz 12, 53111, Bonn, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Hess
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood*; D007093:Imidazoles / Q000737:chemistry*; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000379:methods; D015742:Propofol / Q000097:blood*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013450:Sulfones / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: C524561:1,2-dimethylimidazole-4-sulfonyl chloride; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D013450:Sulfones; D015742:Propofol
keywords: 1,2-Dimethylimidazole-4-sulfonyl chloride (DMISC); Derivatization; LC-MS/MS; Propofol