Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine.
Gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) were compared for their capacity to metabolite identification, sensitivity, and speed of analysis for propofol and its metabolites in urine samples. Acidic hydrolysis, liquid-liquid extraction (LLE), and trimethylsilyl (TMS) derivatization procedures were applied for GC/MS analysis. The LC/MS analysis used a simple sample pretreatment based on centrifugation and dilution. Propofol and four metabolites were successfully analyzed by GC/MS following TMS derivatization. One compound, di-isopropanolphenol was tentatively characterized as a new metabolite observed for the first time in human urine. The TMS derivatization greatly improved the chromatographic properties and detection sensitivity, especially for hydroxylated metabolites. The lower limits of quantitation (LLOQ) of propofol were about 325 and 0.51 ng/mL for the GC/MS scan mode and selected ion monitoring (SIM) mode, respectively. In addition, five conjugated propofol metabolites were successfully analyzed by LC-MS/MS in negative ion mode. The detection sensitivity for these conjugated metabolites could be greatly enhanced by the addition of triethylamine to the mobile phase without any loss of LC resolution capacity. The LLOQs of propofol-glucuronide (PG) were about 1.17 and 2.01 ng/mL for the LC-MS-selected ion monitoring (SIM) and multiple reaction monitoring (MRM) mode, respectively. Both GC/MS and LC/MS methods sensitively detected nine metabolites of propofol and could be used to provide complementary data for the reasonable propofol metabolism study. Urinary excretion profiles for propofol and its metabolites following administration to human were suggested based on the total ion chromatograms obtained by GC/MS and LC/MS methods, respectively.
College of Pharmacy, Kyung Hee University, Seoul 130-701, South Korea.
Sun Young
SY
Lee
Na-Hyun
NH
Park
Eun-Kyung
EK
Jeong
Jae-Woo
JW
Wi
Chang-Ju
CJ
Kim
Jin Young
JY
Kim
Moon Kyo
MK
In
Jongki
J
Hong
D002853:Chromatography, Liquid / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D015742:Propofol / Q000378:metabolism / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D015742:Propofol