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Investigation of plasma concentrations of paracetamol, metacetamol, and orthocetamol in Japanese racehorses using liquid chromatography–electrospray ionisation–tandem mass spectrometry
Author(s) -
Ishii Hideaki,
Obara Taku,
KijimaSuda Isao
Publication year - 2020
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2792
Subject(s) - chemistry , chromatography , pharmacokinetics , electrospray ionization , tandem mass spectrometry , antipyretic , residue (chemistry) , acetaminophen , analgesic , mass spectrometry , liquid chromatography–mass spectrometry , pharmacology , medicine , biochemistry
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.