High-throughput toxicological analysis of propofol in human whole blood by LC-MS

Abstract

A new high-throughput liquid chromatography / mass spectrometry (LC-MS) method for the quantification of propofol in human whole blood was developed and validated. The separation was performed on a Gemini NX column under isocratic conditions using a mixture of 0.05 % ammonium hydroxide in water and methanol (23:77, v/v) with a flow rate of 0.6 mL/min. The detection was performed in SIM mode using an ion trap MS equipped with an APCI ion source using negative mode ionization. The whole blood samples (0.2 mL) were deproteinated with methanol before the analysis. The method showed a good linearity (r > 0.997), precision and accuracy (< 10.2%) over the concentration ranges of 0.05-1.2 μg/mL. The method is not expensive, requires a minimum time for sample preparation and has a run-time of 1.5 min for instrument analysis (retention times for propofol was 0.78 min). The developed and validated LC-MS method is very simple and more rapid than other similar methods. It was successfully applied for the rapid quantification of propofol in human whole blood in forensic toxicology analyses.

Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine

“…The separation of propofol and its metabolites by C18-HPLC, in this study, used a mobile phase modified from previous reports [9,20,21] to improve chromatographic properties and detection sensitivity. To optimize the separation of propofol phase II metabolites, mobile phases (acetonitrile, methanol, acetonitrile-methanol) and concentration of ion-pair Scheme 1.…”

“…Improvement in LC/MS detection sensitivity for propofol in biological samples have also been obtained by chemical derivatization methods [11,19]. For LC/MS analysis, several sample preparation methods including centrifugation [7,[21][22][23], liquid-liquid extraction (LLE) [12,22] and solid-phase extraction (SPE) [4,8,9] have frequently been used. At present, simple sample preparation [7,14,21] based on the centrifugation and dilution also is typically applied for convenient extraction of analytes from biological samples.…”

“…For LC/MS analysis, several sample preparation methods including centrifugation [7,[21][22][23], liquid-liquid extraction (LLE) [12,22] and solid-phase extraction (SPE) [4,8,9] have frequently been used. At present, simple sample preparation [7,14,21] based on the centrifugation and dilution also is typically applied for convenient extraction of analytes from biological samples. Phase II propofol metabolites have been successfully determined by LC-ESI-MS/MS in negative ion mode [8,9]; however, propofol and its phase I metabolites are difficult to protonate or deprotonated which complicates their detection by LC/MS in either positive or negative ion mode.…”

“…The analysis of propofol metabolites in biological samples by LC/MS with either electrospray (ESI) [8,9,11,19] or atmospheric pressure chemical ionization (APCI) [20,21] has become increasingly popular in recent years. Improvement in LC/MS detection sensitivity for propofol in biological samples have also been obtained by chemical derivatization methods [11,19].…”