An interim screening limit of detection for naproxen in equine plasma: a review and analysis

Maylin³

et al. 2022

Ir Vet J

Gabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine. Gabapentin is stable in the environment and routinely detected in urban wastewater. Gabapentin randomly transfers from humans to racing horses and is at times detected at pharmacologically ineffective / trace level concentrations in equine plasma and urine. In Ohio racing between January 2019 and July 2020,18 Gabapentin identifications, all less than 2 ng/ml in plasma, were reported. These identifications were ongoing because the horsemen involved were unable to pin down and therefore avoid the source of these identifications. Given that 44 ng/ml or less is an Irrelevant Plasma Concentration (IPC) of Gabapentin in horses, we proposed a 5 ng/ml plasma interim Screening Limit of Detection for Gabapentin identifications in Ohio racing, and an essentially similar 8 ng/ml plasma Screening Limit of Detection was suggested by a scientific advisor to the Ohio Horse Racing Commission. As such, an analytical Screening Limit of 8 ng /ml in plasma is an appropriate and pharmacologically conservative analytical “cut-off” or Screening Limit of Detection (SLOD) for Gabapentin in equine competitive events to avoid the calling of “positive” identifications on random unavoidable trace level identifications of this widely prescribed human therapeutic medication in equine forensic samples.

“…These proposed screening limits are also well supported by a Tukey outlier analysis [16] performed on the Fig. 2 Ohio State Gabapentin data, presented in Fig.…”

Section: Irrelvant Plasma Concentrations (Ipc) Of Gabapentin In Horsessupporting

confidence: 69%

Section: Irrelvant Plasma Concentrations (Ipc) Of Gabapentin In Horsesmentioning

confidence: 99%

Gabapentin, a human therapeutic medication and an environmental substance transferring at trace levels to horses: a case report

Brewer¹,

Maylin³

et al. 2022

Ir Vet J

“…Such quantitative data are critically important because if sufficient data points become available, they make possible statistical evaluation of the environmental data. These data analyses then provide a scientific basis for any proposed SLODs, as shown by Machin et al 27 in their outlier analysis and resultant proposed SLOD for naproxen in equine plasma samples.…”

Section: Discussionmentioning

confidence: 95%

Case report: Synephrine, a plant substance yielding classic environmental clusters of hay related identifications in equine urine

Brewer

Drug Testing and Analysis

Maylin³

et al. 2022

p-Synephrine, specifically the L-enantiomer, R-(À)-p-Synephrine, 4-[1-hydroxy-2-(methylamino)ethyl] phenol, C 9 H 13 NO 2 , 167.21 g/ mol is a phenylethylamine protoalkaloid/trace amine (Figure 1) found in plants and animals. [1][2][3] In August 2019, there was a reported urinary "presence" of Synephrine in a South African horse show event in Polokwane, fully consistent with local environmental conditions in South Africa (SA), which require a urinary screening limit of detection (SLOD) for Synephrine in horse racing. [4][5][6] Reviewing this matter, we identified 20 or so reported identifications of Synephrine, administratively "adverse analytical findings," in horse racing and sport horse events. 7,8 Furthermore, some of these identifications occurred as classic time and place "clusters," including a sequence of 8 identifications over a 22-day period in March 2019 in Mexico (Table 1). 9,10 We now present our current understanding of the chemical, biological, geographic, and regulatory realities underlying these Synephrine identifications. Based on this analysis, we suggest the in-place South African urinary SLOD of 50 ng/ml, as an interim SLOD for Synephrine and note the need for transparency when regulating substances such as Synephrine, present in both plants and animals across our regionally variable planet. We also note that Synephrine is related to two other plant substances, hordenine 12 and cathinone, 13 (Figure 1) for which SLODs have previously been presented. [12][13][14] | THE SOUTH AFRICAN CASE AND RELATED IDENTIFICATIONS WORLDWIDEThis case report begins with a Synephrine identification reported in a show horse competing at Polokwane, SA, in August, 2019. 15 The person responsible (PR) was a distinguished international competitor, and to our knowledge, neither the horse nor the PR had previous medication violations. The PR became aware of a first Synephrine "positive" in SA when she and the horse returned to SA shortly before the Polokwane event. Her horse was fed standard South African Eragrostis hay from a reputable feedstuff merchant and on August 29, 2019, competed in the Grand Prix class, which event the horse won and was Federation Equestre Internationale (FEI) tested. On

“…Given this circumstance, it is important that reported Aminorex identifications include best good faith estimates of the concentrations of Aminorex identified. These data will allow evaluation of the contributions of geographically different environmental sources to urinary Aminorex identifications and the above interim Screen Limit of Detection can be adjusted if required, following the model presented by [16].…”

Section: Discussionmentioning

confidence: 99%

Aminorex identified in horse urine following consumption of Barbarea vulgaris; a preliminary report

Maylin¹,

Fenger

et al. 2019

Ir Vet J

BackgroundAminorex, (RS)-5- Phenyl-4,5-dihydro-1,3-oxazol-2-amine, is an amphetamine-like anorectic and in the United States a Drug Enforcement Administration [DEA] Schedule 1 controlled substance. Aminorex in horse urine is usually present as a metabolite of Levamisole, an equine anthelmintic and immune stimulant. Recently, Aminorex identifications have been reported in horse urine with no history or evidence of Levamisole administration. Analysis of the urine samples suggested a botanical source, directing attention to the Brassicaceae plant family, with their contained GlucoBarbarin and Barbarin as possible sources of Aminorex. Since horsepersons face up to a 1 year suspension and a $10,000.00 fine for an Aminorex identification, the existence of natural sources of Aminorex precursors in equine feedstuffs is of importance to both individual horsepersons and the industry worldwide.ResultsTesting the hypothesis that Brassicaceae plants could give rise to Aminorex identifications in equine urine we botanically identified and harvested flowering Kentucky Barbarea vulgaris, (“Yellow Rocket”) in May 2018 in Kentucky and administered the plant orally to two horses. Analysis of post-administration urine samples yielded Aminorex, showing that consumption of Kentucky Barbarea vulgaris can give rise to Aminorex identifications in equine urine.ConclusionsAminorex has been identified in post administration urine samples from horses fed freshly harvested flowering Kentucky Barbarea vulgaris, colloquially “Yellow Rocket”. These identifications are consistent with occasional low concentration identifications of Aminorex in equine samples submitted for drug testing. The source of these Aminorex identifications is believed to be the chemically related Barbarin, found as its precursor GlucoBarbarin in Kentucky Barbarea vulgaris and related Brassicaceae plants worldwide.