Stability-indicating normal-phase HPLC method development for separation and quantitative estimation of S-enantiomer of lacosamide in pharmaceutical drug substance and tablet dosage form.

ABSTRACT

Lacosamide (LA) is an antiepileptic medicine that is used to treat tonic-clonic seizures, partial-onset seizures, mental problems, and pain. A simple, effective, and reliable normal-phase liquid chromatographic technique was developed and validated to separate and estimate the enantiomer of (S-enantiomer) LA in pharmaceutical drug substance and drug product. Normal-phase LC was performed using USP L40 packing material (250 × 4.6 mm, 5 µm) and a mobile phase of n-hexane and ethanol at 1.0 ml min-1 . The detection wavelength, column temperature, and injection volume used were 210 nm, 25°C, and 20 µl, respectively. The enantiomers (LA and S-enantiomer) were completely separated using a minimum resolution of 5.8 and accurately quantified without any interference in a 25-min run time. Accuracy study for stereoselective and enantiomeric purity trials was conducted between 10 and 200%, with recovery values ranging from 99.4 to 103.1% and linear regression values >0.997. The stability-indicating characteristics were assessed using forced degradation tests. The proposed normal-phase HPLC technique is an alternate approach to the official monograph methods (USP and Ph.Eur.) of LA, and it was successfully used in the evaluation of release and stability samples for both tablet dosage forms and pharmaceutical substances.