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

Autor:	Dargue R; Division of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK., Grant I; Division of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK., Nye LC; Division of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK., Nicholls A; GlaxoSmithKline R&D, Park Road, Ware, Hertfordshire SG12 0DP, UK., Dare T; GlaxoSmithKline R&D, Park Road, Ware, Hertfordshire SG12 0DP, UK., Stahl SH; ADME Sciences, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Unit 310 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK., Plumb RS; WatersCorporation, Milford, MA 01757, USA., Lee K; Department of Clinical Science & Services, Royal Veterinary College, University of London, Hertfordshire AL9 7TA, UK., Jalan R; UCL Institute for Liver & Digestive Health, Royal Free Hospital, London NW3 2PF, UK., Coen M; Division of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK., Wilson ID; Division of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
Jazyk:	angličtina
Zdroj:	Bioanalysis [Bioanalysis] 2020 Apr; Vol. 12 (7), pp. 485-500. Date of Electronic Publication: 2020 Apr 28.
DOI:	10.4155/bio-2020-0015
Abstrakt:	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.
Databáze:	MEDLINE
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