Lidocaine in the horse: its pharmacological effects and their relationshipto analytical findings

Lidocaine is a local anaesthetic agent that is widely used in equine medici ne. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial p enalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using o ur abaxial sesamoid local anaesthetic model, the highest no-effect dose (HN ED) for the local anaesthetic effect of lidocaine was determined to be 4 mg . Using enzyme-linked immunosorbent assay (ELISA) screening, administration of the HNED of lidocaine to eight horses yielded peak serum and urine conc entrations of apparent lidocaine of 0.84 ng/mL at 30 min and 72.8 ng/mL at 60 min after injection, respectively. These concentrations of apparent lido caine are readily detectable by routine ELISA screening tests (LIDOCAINE EL ISA. Neogen, Lexington, KY). ELISA screening does not specifically identify lidocaine or its metabolites , which include 3-hydroxylidocaine, dimethylaniline, 4-hydroxydimethylanili ne, monoethylglycinexylidine, 3-hydroxymonoethylglycinexylidine, and glycin exylidine. As 3-hydroxylidocaine is the major metabolite recovered from equ ine urine, it was synthesized, purified and characterized, and a quantitati ve mass spectrometric method was developed for 3-hydroxylidocaine as recove red from horse urine. Following subcutaneous (s.c.) injection of the HNED o f lidocaine, the concentration of 3-hydroxylidocaine recovered from urine r eached a peak of about 315 ng/mL at 1 h after administration, The mean pH of the 1 h post dosing urine samples was 7.7, and there was no apparent effect of pH on the amount of 3-hydroxylidocaine recovered. Within the context of these experiments, the data suggests that recovery of less than 315 ng/mL of 3-hydroxylidocaine from a post race urine sample is unlik ely to be associated with a recent local anaesthetic effect of lidocaine, T herefore these data may be of assistance to industry professionals in evalu ating the significance of small concentrations of lidocaine or its metaboli tes in postrace urine samples, It should be noted that the quantitative dat a are based on analytical methods developed specifically for this study, an d that methods used by other laboratories may yield different recoveries of urine 3-hydroxylidocaine.