Synthesis, purification, and chemical characterization of 20-dihydro-6-methylprednisone, an isomeric metabolite of methylprednisolone in the horse, for use as an analytical standard

摘要

Methylprednisolone acetate, pregna-1,4-diene-3,20-dione, 21-(acetoxy)-11,17-dihydro-6-methyl-,(6a,1ip)-, is a synthetic gluco-corticoid pro-drug widely used in equine medicine. It is recognized as a therapeutic medication by many equine organizations, including the American Association of Equine Practitioners (AAEP), the Racing Medication and Testing Consortium (RMTC), the Association of Racing Commissioners International (ARCI), and numerous racing and other regulatory authorities in the United States and elsewhere. As such, methylprednisolone is widely used on horses in training, usually as the long-acting Depo-medrol formulation administered by intra-articular or intra-muscular injection. With respect to racing and other equine performance events, its use as a controlled therapeutic medication on horses in training is regulated by the testing of plasma and/or urine, but usually by application of a quantitative regulatory threshold in plasma. For example, the RMTC lists methylprednisolone as a 'controlled therapeutic medication' and sets forth that a 100 pg/mL methylprednisolone threshold in plasma or serum corresponds to a seven-day 'restricted administration time' (withdrawal time) following intra-articular administration of a '100 mg total in one intra-articular space'.