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

Abstract

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 (0.1 mL) were precipitated with -20.0°C acetonitrile after addition of the internal standard, daidzein. Separation was achieved with a Phenomenex® Luna® C₁₈ (2) (5 µm, 250 × 4.60 mm) column with ultraviolet detection at 210 nm. The calibration curves were linear ranging from 0.5 to 25 µg/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 0.5 µg/mL. The assay was applied successfully to a pre-clinical study of lacosamide pharmacokinetics in dogs.

A fully validated method for the determination of lacosamide in human plasma using gas chromatography with mass spectrometry: Application for therapeutic drug monitoring

“…Lacosamide [( R )‐2‐acetamido‐ N ‐benzyl‐3‐methoxypropionamide] (Fig. ) is a functionalized amino acid with anticonvulsant properties that was approved from the United States Food and Drug Administration (FDA) in 2008 . In the same year, lacosamide was licensed in Europe as an antiepileptic drug for the adjunctive treatment of partial‐onset seizures, with or without secondary generalization, under the trade name Vimpat® (UCB), in patients with epilepsy aged 16 and older .…”

“…) is a functionalized amino acid with anticonvulsant properties that was approved from the United States Food and Drug Administration (FDA) in 2008 . In the same year, lacosamide was licensed in Europe as an antiepileptic drug for the adjunctive treatment of partial‐onset seizures, with or without secondary generalization, under the trade name Vimpat® (UCB), in patients with epilepsy aged 16 and older . Nevertheless, there are few published studies that report the use of lacosamide in children or young people (aged 1–21) for the treatment of refractory epilepsy seizures .…”

“…In most of these cases, the seizure frequency was decreased like it happens with adults . Lacosamide is a dual mode action drug as it selectively enhances slow inactivation of sodium channel, and it also binds to the collapsin response mediator protein‐2, which is involved in the modulation of pain transmission . The drug is also effective in the treatment of painful diabetic neuropathy .…”

“…All published methods for the determination of lacosamide in biological samples use LC . To our knowledge, there is no validated method in the literature for the determination of lacosamide using GC–MS.…”

A simple and versatile method for microencapsulation of anti-epileptic drugs for focal therapy of epilepsy

“…This extraction procedure was repeated four times with each methanol sample allowed to evaporate to leave residual drug behind which was reconstituted using artificial cerebrospinal fluid (aCSF, 0.866 wt% NaCl, 0. , and the UV-vis detection wavelength was 210 nm. 33 The amounts of released drug were calculated according to a pre-established calibration curve that was obtained by plotting the peak areas against respective concentrations of a range of standard lacosamide solutions prepared in aCSF.…”