3-Methoxytyrosine as an indicator of dopaminergic manipulation in equine plasma.

Keen, B; Cawley, A; Reedy, B; Noble, G; Loy, J; Fu, S

3-Methoxytyrosine as an indicator of dopaminergic manipulation in equine plasma.

Keen, B

Cawley, A Reedy, B

Noble, G Loy, J Fu, S

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: J Chromatogr B Analyt Technol Biomed Life Sci, 2023, 1220, pp. 123652
Issue Date:: 2023-04-01

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Field	Value	Language
dc.contributor.author	Keen, B https://orcid.org/0000-0002-1955-2951
dc.contributor.author	Cawley, A
dc.contributor.author	Reedy, B https://orcid.org/0000-0003-1797-8091
dc.contributor.author	Noble, G
dc.contributor.author	Loy, J
dc.contributor.author	Fu, S https://orcid.org/0000-0002-6238-3612
dc.date.accessioned	2023-04-18T21:36:39Z
dc.date.available	2023-02-23
dc.date.available	2023-04-18T21:36:39Z
dc.date.issued	2023-04-01
dc.identifier.citation	J Chromatogr B Analyt Technol Biomed Life Sci, 2023, 1220, pp. 123652
dc.identifier.issn	1570-0232
dc.identifier.issn	1873-376X
dc.identifier.uri	http://hdl.handle.net/10453/169964
dc.description.abstract	The use of catechol-O-methyltransferase inhibitors may mask doping agents, primarily levodopa, administered to racehorses and prolong the stimulating effects of dopaminergic compounds such as dopamine. It is known that 3-methoxytyramine is a metabolite of dopamine and 3-methoxytyrosine is a metabolite of levodopa thus these compounds are proposed to be potential biomarkers of interest. Previous research established a urinary threshold of 4,000 ng/mL for 3-methoxytyramine to monitor misuse of dopaminergic agents. However, there is no equivalent biomarker in plasma. To address this deficiency a rapid protein precipitation method was developed and validated to isolate target compounds from 100 µL equine plasma. A liquid chromatography-high resolution accurate mass (LC-HRAM) method using an IMTAKT Intrada amino acid column provided quantitative analysis of 3-methoxytyrosine (3-MTyr) with lower limit of quantification of 5 ng/mL. Reference population profiling (n = 1129) investigated the expected basal concentrations for raceday samples from equine athletes and showed a right-skewed distribution (skewness = 2.39, kurtosis = 10.65) which resulted from large variation (RSD = 71%) within the data. Logarithmic transformation of the data provided a normal distribution (skewness = 0.26, kurtosis = 3.23) resulting in the proposal of a conservative threshold for plasma 3-MTyr of 1,000 ng/mL at a 99.995% confidence level. A 12-horse administration study of Stalevo® (800 mg L-DOPA, 200 mg carbidopa, 1600 mg entacapone) revealed elevated 3-MTyr concentrations for 24-hours post-administration.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier
dc.relation.ispartof	J Chromatogr B Analyt Technol Biomed Life Sci
dc.relation.isbasedon	10.1016/j.jchromb.2023.123652
dc.rights	info:eu-repo/semantics/embargoedAccess
dc.subject	0301 Analytical Chemistry, 0601 Biochemistry and Cell Biology, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.mesh	Horses
dc.subject.mesh	Animals
dc.subject.mesh	Levodopa
dc.subject.mesh	Dopamine
dc.subject.mesh	Catechol O-Methyltransferase
dc.subject.mesh	Carbidopa
dc.subject.mesh	Catechols
dc.subject.mesh	Animals
dc.subject.mesh	Horses
dc.subject.mesh	Dopamine
dc.subject.mesh	Levodopa
dc.subject.mesh	Carbidopa
dc.subject.mesh	Catechols
dc.subject.mesh	Catechol O-Methyltransferase
dc.title	3-Methoxytyrosine as an indicator of dopaminergic manipulation in equine plasma.
dc.type	Journal Article
utslib.citation.volume	1220
utslib.location.activity	Netherlands
utslib.for	0301 Analytical Chemistry
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CFS - Centre for Forensic Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	embargoed	*
utslib.copyright.embargo	2025-04-01T00:00:00+1000Z
dc.date.updated	2023-04-18T21:36:38Z
pubs.publication-status	Published
pubs.volume	1220

Abstract:

The use of catechol-O-methyltransferase inhibitors may mask doping agents, primarily levodopa, administered to racehorses and prolong the stimulating effects of dopaminergic compounds such as dopamine. It is known that 3-methoxytyramine is a metabolite of dopamine and 3-methoxytyrosine is a metabolite of levodopa thus these compounds are proposed to be potential biomarkers of interest. Previous research established a urinary threshold of 4,000 ng/mL for 3-methoxytyramine to monitor misuse of dopaminergic agents. However, there is no equivalent biomarker in plasma. To address this deficiency a rapid protein precipitation method was developed and validated to isolate target compounds from 100 µL equine plasma. A liquid chromatography-high resolution accurate mass (LC-HRAM) method using an IMTAKT Intrada amino acid column provided quantitative analysis of 3-methoxytyrosine (3-MTyr) with lower limit of quantification of 5 ng/mL. Reference population profiling (n = 1129) investigated the expected basal concentrations for raceday samples from equine athletes and showed a right-skewed distribution (skewness = 2.39, kurtosis = 10.65) which resulted from large variation (RSD = 71%) within the data. Logarithmic transformation of the data provided a normal distribution (skewness = 0.26, kurtosis = 3.23) resulting in the proposal of a conservative threshold for plasma 3-MTyr of 1,000 ng/mL at a 99.995% confidence level. A 12-horse administration study of Stalevo® (800 mg L-DOPA, 200 mg carbidopa, 1600 mg entacapone) revealed elevated 3-MTyr concentrations for 24-hours post-administration.

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http://hdl.handle.net/10453/169964