Quantitative analysis of paracetamol, metacetamol, and orthocetamol in equine urine from racehorses in Japan using liquid chromatography-electrospray ionization-tandem mass spectrometry.
Abstract: Paracetamol is commonly used as an over-the-counter analgesic and antipyretic medication for humans, but not sold as a legitimate therapeutic medication for horses in Japan. However, paracetamol is commonly found in horses together with its two isomers, metacetamol and orthocetamol. We previously reported that paracetamol and orthocetamol were both present in selected feed consumed by Japanese racehorses. For the purpose of the doping control of paracetamol in local Japanese horses, we proposed establishing residue limits (Japanese residue limits, JRLs) to minimize the risk of reporting paracetamol from environmental contributions and to differentiate its presence from active administration. Recently, we proposed a preliminary JRL for paracetamol in equine plasma based on a population study of more than 300 Japanese racehorses. In this paper, we will present our studies on the urinary concentrations of paracetamol, metacetamol, and orthocetamol in postrace samples collected from 403 Japanese racehorses over a 1 year period, detected using liquid chromatography-electrospray ionization-tandem mass spectrometry. Our results revealed that the hydrolyzed urinary concentrations of paracetamol, metacetamol, and orthocetamol were in the range 15.7-2,360 ng/mL (median 363 ng/mL), 8.07-382 ng/mL (84.5 ng/mL), and 919-74,418 ng/mL (13,475 ng/mL), respectively. Based on our statistical model, the preliminary JRL of hydrolyzed paracetamol in equine urine was determined to be 7,400 ng/mL, at a risk factor of 1 in 10,000. Further investigations will be required to demonstrate the applicability and validity of our preliminary plasma and urine JRLs to local Japanese racehorses.
© 2020 John Wiley & Sons, Ltd.
Publication Date: 2020-06-24 PubMed ID: 32436292DOI: 10.1002/dta.2860Google Scholar: Lookup
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- Journal Article
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Summary
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This research aims to establish a preliminary limit for the presence of paracetamol and its counterparts, metacetamol and orthocetamol, in the urine of racehorses in Japan. The study uses the method of liquid chromatography-electrospray ionization-tandem mass spectrometry to trace these substances. The outcome will help to distinguish the presence of these substances due to environmental influences from active administration, hence serving in doping control.
Objective and Context
- The researchers’ primary objective is to establish residue limits, termed as “Japanese Residue Limits” (JRLs), for paracetamol and its isomers – metacetamol and orthocetamol – in the urine of racehorses. This is intended to minimize the reporting of paracetamol from environmental sources and aid in distinguishing its presence due to active administration.
- While paracetamol is not sold as a therapeutic drug for horses in Japan, it is frequently found in racehorses and in their feed. Therefore, setting a residue limit for paracetamol is necessary for helping control potentially harmful substances found in racehorses.
Methodology
- Principally, the study drew upon a sample set of 403 Japanese racehorses.
- The researchers employed liquid chromatography-electrospray ionization-tandem mass spectrometry to detect and measure the urinary concentrations of paracetamol, metacetamol, and orthocetamol in samples taken from these horses over a one-year period.
Findings
- The urinary concentrations of paracetamol, metacetamol, and orthocetamol were found to be in specific ranges, with a considerable difference between the lowest and highest concentrations. Medians for the three substances were also calculated.
- Using a statistical model, the researchers determined a preliminary JRL for hydrolyzed paracetamol in equine urine to be 7,400 ng/mL, at a risk factor of 1 in 10,000.
Implications and Next Steps
- The findings provide a stepping stone in establishing a residue limit for paracetamol and its isomers in horse urine, thereby aiding in doping control.
- However, further investigation is needed to verify and apply the preliminary plasma and urine JRLs to local Japanese racehorses in a broader context. The researchers express the necessity to ensure the applicability and validity of these preliminary limits in succeeding studies.
Cite This Article
APA
Ishii H, Obara T, Kusano K, Kijima-Suda I.
(2020).
Quantitative analysis of paracetamol, metacetamol, and orthocetamol in equine urine from racehorses in Japan using liquid chromatography-electrospray ionization-tandem mass spectrometry.
Drug Test Anal, 12(8), 1196-1202.
https://doi.org/10.1002/dta.2860 Publication
Researcher Affiliations
- Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2, Tsuruta-machi, Utsunomiya, Tochigi, 320-0851, Japan.
- Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
- Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
- Administration Division Race Horse Hospital Ritto Training Center, Japan Racing Association, 1028, Misono, Ritto, Shiga, 520-3085, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2, Tsuruta-machi, Utsunomiya, Tochigi, 320-0851, Japan.
MeSH Terms
- Acetaminophen / analysis
- Acetaminophen / chemistry
- Acetaminophen / pharmacokinetics
- Animals
- Chromatography, Liquid / methods
- Chromatography, Liquid / veterinary
- Doping in Sports / prevention & control
- Drug Residues / analysis
- Horses
- Japan
- Models, Statistical
- Spectrometry, Mass, Electrospray Ionization / methods
- Spectrometry, Mass, Electrospray Ionization / veterinary
- Substance Abuse Detection / methods
- Substance Abuse Detection / veterinary
- Tandem Mass Spectrometry / methods
- Tandem Mass Spectrometry / veterinary
References
This article includes 9 references
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Citations
This article has been cited 2 times.- Liu S, Yu Y, Ni K, Liu T, Gu M, Wu Y, Du G, Ran X. Construction of a novel electrochemical sensor based on biomass material nanocellulose and its detection of acetaminophen.. RSC Adv 2022 Sep 28;12(43):27736-27745.
- 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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