Quantitative LC/MS/MS analysis of acetaminophen–cysteine adducts (APAP–CYS) and its application in acetaminophen overdose patients

Taha, Hairin and Rahman, Marzilawati Abdul and Haron, Didi Erwandi Mohamad and Mahadeva, Sanjiv and Kee, Lee Yean and Abd Rahman, Noorsaadah and Mohd, Mustafa Ali and Chik, Zamri (2013) Quantitative LC/MS/MS analysis of acetaminophen–cysteine adducts (APAP–CYS) and its application in acetaminophen overdose patients. Analytical Methods, 5. pp. 1955-1964. ISSN 1759-9679, DOI https://doi.org/10.1039/C3AY26614A.

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Official URL: https://doi.org/10.1039/C3AY26614A

Abstract

A more sensitive approach by liquid chromatography–tandem mass spectrometry (LC/MS/MS) method using the AB Sciex QTRAP 5500 was developed and validated for the detection and quantification of acetaminophen–cysteine adducts (APAP–CYS) in human plasma. Chromatographic separation was achieved using a Protecol P C18 column (2.1 mm i.d. × 100 mm, 3 microns). The mobile phase consists of A: 2 mM ammonium formate in water (0.2% formic acid) and B: 2 mM ammonium formate in acetonitrile (0.2% formic acid). The analysis was performed using positive and negative ion electrospray ionization (ESI) in multiple reaction monitoring mode (MRM) with a total run time of 7 min per assay. The MS/MS ion transitions monitored were m/z 271 → 140 for APAP–CYS (positive mode) and m/z 154 → 111 for acetaminophen-D4 (negative mode). The newly developed method showed good linearity in the range of 1.0 to 100 ng mL−1. Inter and intra batch precision and accuracy of the method ranged from 0.28 to 5.30% and 87.0 to 113% respectively. LOD was 0.5 ng mL−1 and LLOQ was 1.0 ng mL−1. Analytes were extracted from plasma samples by simple protein precipitation using acetonitrile. The method was successfully applied in a preliminary clinical study to determine APAP–CYS concentration from 46 acetaminophen overdose patients treated at outpatient clinic in the University Malaya Medical Centre.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: Liquid chromatography–tandem mass spectrometry (LC/MS/MS); Acetaminophen–cysteine adducts (APAP–CYS); Acetaminophen overdose patients
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
R Medicine
Divisions: Faculty of Medicine
Faculty of Science > Department of Chemistry
Depositing User: Ms Haslinda Lahuddin
Date Deposited: 15 Jul 2013 01:37
Last Modified: 10 Oct 2018 06:46
URI: http://eprints.um.edu.my/id/eprint/7274

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