High-performance liquid chromatographic analysis of lacosamide in canine serum using ultraviolet detection: Application to pre-clinical pharmacokinetics in dogs

摘要

A method for analysis of lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropionamide] is needed for both human and veterinary pharmacokinetic investigations. While lacosamide is currently used to manage partial-onset seizures in humans suffering from epilepsy, it is also presently being investigated for use in the treatment of canine epilepsy in veterinary medicine. Currently, no dosing regimen for the drug exists in dogs. A novel and simple high-performance liquid chromatography method was developed for determination of lacosamide in dog serum. Serum proteins (0.1mL) were precipitated with -20.0°C acetonitrile after addition of the internal standard, daidzein. Separation was achieved with a Phenomenex? Luna? C 18 (2) (5μm, 250×4.60mm) column with ultraviolet detection at 210nm. The calibration curves were linear ranging from 0.5 to 25μg/mL. Precision of the assay was 13% (RSD) and was within 12% for all points in the calibration curve. The limit of quantitation for this method was 0.5μg/mL. The assay was applied successfully to a pre-clinical study of lacosamide pharmacokinetics in dogs.