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

Abstract

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

20-Hydroxyecdysone identification in performance horses – case reports and review

“…As the sensitivity of equine drug testing has increased there have been concomitant increases in the incidence of detections of plant substances. These identifications have led the International Federation of Horseracing Authorities (IFHA) to recommend Residue Limits for a number of such substances [21] , many of which are plant substances that directly transfer from consumed plants to horses, e.g., atropine, scopolamine, and hordenine [16,4,5] . One characteristic of these plant related substance identifications is that the likelihood of transfer of a pasture plant substance to a horse can depend to a significant extent on local seasonal and environmental conditions.…”

“…One characteristic of these plant related substance identifications is that the likelihood of transfer of a pasture plant substance to a horse can depend to a significant extent on local seasonal and environmental conditions. In this regard the classic examples are hordenine [16] , synephrine [5] and scopolamine [4] , the inadvertent transfer to horses of each of these substances being to a significant extent driven by both regional and seasonal factors.…”