Abstract

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.

Highlights

  • Paracetamol/acetaminophen (N-acetyl-para-aminophenol; APAP) is an analgesic and antipyretic agent [1,2,3,4,5]

  • Paracetamol possesses an analgesic mechanism of action that is a very complex process, in which both peripheral and central antinociceptive processes must be considered, as well as the redox mechanism [2]

  • It is widely used in human medicine over the counter (OTC) painkillers because of its effective action and relative safety [1,4,8,9]

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Summary

Introduction

Paracetamol/acetaminophen (N-acetyl-para-aminophenol; APAP) is an analgesic and antipyretic agent [1,2,3,4,5]. Paracetamol was synthesized in 1878 [2], clinically used in 1887 [6], and first marketed to consumers in the 1950s in the USA [7], its mechanism of action is still not fully understood [1,2,4] It provides analgesic and antipyretic effects similar to nonsteroidal anti-inflammatory drugs (NSAIDs) but does not produce any antiinflammatory effects [1,2]. Paracetamol possesses an analgesic mechanism of action that is a very complex process, in which both peripheral and central antinociceptive processes must be considered, as well as the redox mechanism [2] It is widely used in human medicine over the counter (OTC) painkillers because of its effective action and relative safety (at therapeutic doses) [1,4,8,9]. Paracetamol is classified as a pharmacologically acceptable active substance for use in pigs, but no maximum residue limit (MRL) has been established for this compound so far [13]

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