title: Quantification of acetaminophen and two of its metabolites in human plasma by ultra-high performance liquid chromatography-low and high resolution tandem mass spectrometry.
abstract: The quantification of acetaminophen (APAP) and two of its metabolites, i.e. acetaminophen-glucuronide (APAP-GLUC) and acetaminophen-cysteine (APAP-CYS), is described in human plasma using ultra-high performance liquid chromatography coupled to a triple quadrupole linear ion trap mass spectrometer operating in the selected reaction monitoring (SRM/MS) mode and to a high resolution quadrupole time-of -flight mass spectrometer operating in the MS/MS (HR-SRM/MS) mode. Starting with a 50 μL plasma aliquot, a generic sample preparation was performed using protein precipitation with methanol/ethanol. Both methods were found to be linear over 2.5 orders of magnitude. Similar performances to the SRM/MS assay were obtained for APAP, APAP-CYS and APAP-GLUC using high resolution-selected reaction monitoring mode with LLOQ of 20, 50 and 50 ng/mL, respectively. For all analytes, precision was found to be better than 12% and accuracy in the range 90.3-109%. The present study demonstrates the ability of QqTOF platforms for accurate and precise quantification in MS/MS mode using short duty cycle with similar sensitivity to LC-SRM/MS. Additionally, as full scan data MS(ALL) are available qualitative and quantitative information on metabolites can also be obtained in a single LC-MS run.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Life Sciences Mass Spectrometry, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Tonoli
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Varesio
authors.forename: Gérard
authors.initials: G
authors.lastname: Hopfgartner
mesh_terms: D000082:Acetaminophen / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000082:Acetaminophen