Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues

Paracetamol/acetaminophen (APAP) is one of the most popular pharmacologically active substances used as an analgesic and antipyretic agent. The metabolism of this drug occurs in the liver and leads to the formation of two main metabolites—glucuronic acid and sulfate derivate. Despite the wide use of...

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Main Authors: Konrad Pietruk, Małgorzata Gbylik-Sikorska, Beata Łebkowska-Wieruszewska, Anna Gajda, Mario Giorgi, Irene Sartini, Piotr Jedziniak
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/7/2046
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spelling doaj-cad89f1d558b46a9bbf6d15a550275e62021-04-02T23:07:04ZengMDPI AGMolecules1420-30492021-04-01262046204610.3390/molecules26072046Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal TissuesKonrad Pietruk0Małgorzata Gbylik-Sikorska1Beata Łebkowska-Wieruszewska2Anna Gajda3Mario Giorgi4Irene Sartini5Piotr Jedziniak6Department of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, PolandDepartment of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, PolandDepartment of Pharmacology, Toxicology and Environmental Protection, University of Life Sciences, 20-950 Lublin, PolandDepartment of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, PolandDepartment of Veterinary Sciences, University of Pisa, 56126 Pisa, ItalyDepartment of Veterinary Medicine, PhD School, University of Sassari, 07100 Sassari, ItalyDepartment of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, PolandParacetamol/acetaminophen (APAP) is one of the most popular pharmacologically active substances used as an analgesic and antipyretic agent. The metabolism of this drug occurs in the liver and leads to the formation of two main metabolites—glucuronic acid and sulfate derivate. Despite the wide use of paracetamol in veterinary medicine, a handful of analytical methods were published for the determination of paracetamol residues in animal tissues. In this paper, a multimatrix method has been developed for the determination of paracetamol and two metabolites—paracetamol sulfate (PS) and p-Acetamidophenyl β-D-glucuronide (PG). A validation procedure was conducted to verify method reliability and fit purpose as a tool for analyzing acetaminophen and metabolites in muscle, liver, lung, and kidney samples from different species of animals. Established validation parameters were in agreement with acceptable criteria laid by the European legislation. The initial significant matrix effect was successfully reduced by implementing an internal standard—4-Acetamidophenyl β-D-glucuronide-d3 (PG-d3, IS). The usefulness of the developed method was verified by analyzing samples from an experiment in which paracetamol was administrated to geese.https://www.mdpi.com/1420-3049/26/7/2046paracetamolmetabolitesmuscleheartlungsliver
collection DOAJ
language English
format Article
sources DOAJ
author Konrad Pietruk
Małgorzata Gbylik-Sikorska
Beata Łebkowska-Wieruszewska
Anna Gajda
Mario Giorgi
Irene Sartini
Piotr Jedziniak
spellingShingle Konrad Pietruk
Małgorzata Gbylik-Sikorska
Beata Łebkowska-Wieruszewska
Anna Gajda
Mario Giorgi
Irene Sartini
Piotr Jedziniak
Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues
Molecules
paracetamol
metabolites
muscle
heart
lungs
liver
author_facet Konrad Pietruk
Małgorzata Gbylik-Sikorska
Beata Łebkowska-Wieruszewska
Anna Gajda
Mario Giorgi
Irene Sartini
Piotr Jedziniak
author_sort Konrad Pietruk
title Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues
title_short Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues
title_full Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues
title_fullStr Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues
title_full_unstemmed Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues
title_sort development of a multimatrix uhplc-ms/ms method for the determination of paracetamol and its metabolites in animal tissues
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2021-04-01
description Paracetamol/acetaminophen (APAP) is one of the most popular pharmacologically active substances used as an analgesic and antipyretic agent. The metabolism of this drug occurs in the liver and leads to the formation of two main metabolites—glucuronic acid and sulfate derivate. Despite the wide use of paracetamol in veterinary medicine, a handful of analytical methods were published for the determination of paracetamol residues in animal tissues. In this paper, a multimatrix method has been developed for the determination of paracetamol and two metabolites—paracetamol sulfate (PS) and p-Acetamidophenyl β-D-glucuronide (PG). A validation procedure was conducted to verify method reliability and fit purpose as a tool for analyzing acetaminophen and metabolites in muscle, liver, lung, and kidney samples from different species of animals. Established validation parameters were in agreement with acceptable criteria laid by the European legislation. The initial significant matrix effect was successfully reduced by implementing an internal standard—4-Acetamidophenyl β-D-glucuronide-d3 (PG-d3, IS). The usefulness of the developed method was verified by analyzing samples from an experiment in which paracetamol was administrated to geese.
topic paracetamol
metabolites
muscle
heart
lungs
liver
url https://www.mdpi.com/1420-3049/26/7/2046
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