Residue definition of lignocaine and bupivacaine in sheep and cattle

Summary

The red meat industry needs access to pain relief products to ensure high standards of animal welfare are met during surgical interventions. Presently Minimum Residue Limits (MRL’s), Withholding Periods (WHP’s) and Export Slaughter Intervals (ESI’s) are not available for the local anaesthetics lignocaine and bupivacaine in sheep and cattle, nor for the various metabolites produced when the drugs are broken down in the body.

Lignocaine and bupivacaine were administered to sheep and cattle in a pilot study to define the residue of these drugs. Highly sensitive QuEChERS- based HPLC-MS/MS methods were developed to measure parent drug and potential metabolites in plasma, urine and edible tissues. Disposition kinetics of both local anaesthetics and their metabolites were established. Parent molecule residues were detected in tissues up to 7 days post-administration of both local anaesthetics.

An important species difference in metabolism was discovered: cattle metabolise lignocaine primarily to 2,6-dimethylaniline (DMA, also called 2,6-xylidine) whereas DMA is only a minor metabolite in sheep. DMA is not a metabolite of bupivacaine in either species. These findings are important because DMA has been found to possess mutagenic and genotoxic properties, and is a genotoxic carcinogenic in rats.

For registration of lignocaine and/or bupivacaine a residue definition will need to be established  for the purpose of calculating MRL’s, WHP’s and ESI’s; results of the current study will help design appropriate protocols.