Mepivacaine: its pharmacological effects and their relationship to analytical findings in the horse

Mepivacaine is a local anaesthetic drug that is widely used in equine medic ine and is classified by the Association of Racing Commissioners Internatio nal (ARCI) as a Class 2 foreign substance that may cause regulators to impo se significant penalties if residues are identified in post-race urine samp les. Therefore, an analytical/pharmacological database was developed for th is agent and its metabolites. Using an abaxial sesamoid local anaesthetic m odel, it was determined that the highest no-effect dose (HNED) for its loca l anaesthetic effect was 2 mg. Using enzyme-linked immunosorbent assay (ELI SA) screening, it was determined that subcutaneous (s.c,) administration of the HNED of mepivacaine to eight horses yielded a peak urinary concentrati on of apparent mepivacaine of 63 ng/mL 2 h after injection. The major identified metabolite recovered from equine urine after dosing wi th mepivacaine is 3-hydroxymepivacaine. Therefore, 3-hydroxymepivacaine was synthesized, purified and characterized, and a quantitative mass spectrome tric method was developed for this metabolite as isolated from horse urine. Following subcutaneous injection of the HNED of mepivacaine, the concentra tion of 3-hydroxymepivacaine recovered from horse urine reached a peak of a bout 64.6 ng/mL at 4 h after administration as measured by GC/MS. The concentration of mepivacaine or its metabolites after administration of a HNED dose are detectable by mass spectral techniques. Within the limits of this research, the study suggests that recovery of concentrations less t han about 65 ng/mL of 3-hydroxymepivacaine from post-race urine samples may not be associated with a recent LA effect of mepivacaine.