Investigation of plasma concentrations of paracetamol, metacetamol, and orthocetamol in Japanese racehorses using liquid chromatography-electrospray ionisation-tandem mass spectrometry.
Abstract: Paracetamol is used widely as an over-the-counter analgesic and antipyretic medication for humans, but not for Japanese racehorses. Paracetamol can be an environmental substance, and is found together with its two isomers, metacetamol and orthocetamol, in equine urine. However, the sources and routes of paracetamol exposure remain unclear. To control the misuse of paracetamol, it is appropriate to establish residue limits for paracetamol to differentiate the administration of paracetamol from its environmental levels. In this study, we developed and validated a quantitative method for paracetamol, metacetamol, and orthocetamol in equine plasma using liquid chromatography-electrospray ionization-tandem mass spectrometry and applied it to postrace samples from 320 Japanese racehorses for approximately 1 year. In addition, we conducted feed analysis and related pharmacokinetics simulations to evaluate the contributions from exposure via feed. The hydrolyzed plasma concentrations of paracetamol, metacetamol, and orthocetamol ranged from 0.787 to 39.8 ng/mL (median 5.87 ng/mL), 0 to 2.13 ng/mL (0.347 ng/mL), and 1.98 to 82.8 ng/mL (16.6 ng/mL), respectively. Such low concentrations of paracetamol were deemed irrelevant to therapeutic effect. Based on statistical analysis, the preliminary Japanese residue limits of unhydrolyzed and hydrolyzed paracetamol were determined to be 70.5 ng/mL and 112 ng/mL, respectively, in plasma, at a risk factor of 1 in 10,000. Furthermore, we detected paracetamol and orthocetamol in feed samples. A pharmacokinetics simulation showed that the presence of orthocetamol is most probably related to daily feed rations. As for paracetamol, feed can be one of the sources and other possible sources require further investigation.
© 2020 John Wiley & Sons, Ltd.
Publication Date: 2020-04-01 PubMed ID: 32187884DOI: 10.1002/dta.2792Google Scholar: Lookup
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- Journal Article
- Validation Study
Summary
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The researchers investigated how much of the common painkillers paracetamol, metacetamol, and orthocetamol are found in Japanese racehorses, checked the levels in their feed, and used a testing method called liquid chromatography-electrospray ionization-tandem mass spectrometry to do this.
Objective of the Study
- The study aimed to establish residue limits for paracetamol to differentiate administration of the drug from environmental levels particularly in Japanese racehorses.
- It also sought to understand the amounts of paracetamol and its isomers, metacetamol and orthocetamol, in equine plasma and evaluate their sources and levels of exposure.
Methodology
- The investigation employed a method known as liquid chromatography-electrospray ionization-tandem mass spectrometry to analyze the concentrations of the drug compounds in equine plasma.
- The researchers also performed a feed analysis and conducted pharmacokinetics simulations to assess any exposure from this source.
- They used these techniques to test post-race samples from 320 Japanese racehorses over a one-year period.
Findings
- They found that the plasma concentrations of paracetamol, metacetamol and orthocetamol were low, showing the paracetamol had no therapeutic effect at such levels.
- Based on the statistical analysis, they established preliminary residue limits for paracetamol—in both unhydrolyzed and hydrolyzed forms—in plasma. They calculated that the risk factor at these limits is 1 in 10,000.
- They also detected the presence of paracetamol and orthocetamol in feed samples. A simulation suggested the presence of orthocetamol was most likely linked to the daily ration feed.
- While the study identified feed as one possible source of paracetamol, the researchers suggested that further investigations are needed to identify other potential sources.
Cite This Article
APA
Ishii H, Obara T, Kijima-Suda I.
(2020).
Investigation of plasma concentrations of paracetamol, metacetamol, and orthocetamol in Japanese racehorses using liquid chromatography-electrospray ionisation-tandem mass spectrometry.
Drug Test Anal, 12(7), 929-937.
https://doi.org/10.1002/dta.2792 Publication
Researcher Affiliations
- Laboratory of Racing Chemistry, Utsunomiya, Tochigi, Japan.
- Tohoku University Hospital, Tohoku University, Sendai, Japan.
- Tohoku University Hospital, Tohoku University, Sendai, Japan.
- Laboratory of Racing Chemistry, Utsunomiya, Tochigi, Japan.
MeSH Terms
- Acetaminophen / analysis
- Acetaminophen / chemistry
- Acetaminophen / pharmacokinetics
- Animal Feed / analysis
- Animals
- Chromatography, Liquid / methods
- Chromatography, Liquid / veterinary
- Computer Simulation
- Drug Residues / analysis
- Drug Residues / chemistry
- Horses
- Isomerism
- Japan
- Spectrometry, Mass, Electrospray Ionization / methods
- Spectrometry, Mass, Electrospray Ionization / veterinary
- Tandem Mass Spectrometry / methods
- Tandem Mass Spectrometry / veterinary
References
This article includes 12 references
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Citations
This article has been cited 2 times.- Mercer MA, Davis JL, McKenzie HC. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses. Animals (Basel) 2023 May 10;13(10).
- Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN. Generic approach for the discovery of drug metabolites in horses based on data-dependent acquisition by liquid chromatography high-resolution mass spectrometry and its applications to pharmacokinetic study of daprodustat. Anal Bioanal Chem 2022 Nov;414(28):8125-8142.
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