The analysis of acetaminophen (paracetamol) and seven metabolites in rat, pig and human plasma by U(H)PLC–MS

Dargue, R; Grant, I; Nye, L C; Nicholls, A; Dare, T; Stahl, S H; Plumb, R S; Lee, K C L

Abstract

A U(H)PLC–MS/MS method is described for the analysis of acetaminophen and its sulphate, glucuronide, glutathione, cysteinyl and N-acetylcysteinyl metabolites in plasma using stable isotope-labeled internal standards. P-Aminophenol glucuronide and 3-methoxyacetaminophen were monitored and semi-quantified using external standards. The assay takes 7.5 min/sample, requires only 5 μl of plasma and involves minimal sample preparation. The method was validated for rat plasma and cross validated for human and pig plasma and mouse serum. LOQ in plasma for these analytes were 0.44 μg/ml (APAP-C), 0.58 μg/ml (APAP-SG), 0.84 μg/ml (APAP-NAC), 2.75 μg/ml (APAP-S), 3.00 μg/ml (APAP-G) and 16 μg/ml (APAP). Application of the method is illustrated by the analysis of plasma following oral administration of APAP to male Han Wistar rats.

Citation

Dargue, R., Grant, I., Nye, L. C., Nicholls, A., Dare, T., Stahl, S. H., Plumb, R. S., & Lee, K. C. L. (2020). The analysis of acetaminophen (paracetamol) and seven metabolites in rat, pig and human plasma by U(H)PLC–MS. Bioanalysis, 12(7), https://doi.org/10.4155/bio-2020-0015

• Journal Article Type: Article
• Acceptance Date: Mar 23, 2020
• Publication Date: Apr 28, 2020
• Deposit Date: May 11, 2020
• Publicly Available Date: May 11, 2020
• Journal: Bioanalysis
• Print ISSN: 1757-6180
• Electronic ISSN: 1757-6199
• Publisher: Newlands Press
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 7
• DOI: https://doi.org/10.4155/bio-2020-0015
• Public URL: https://rvc-repository.worktribe.com/output/1377593