Identification of forced degradation products of lacosamide by LC-QQLIT-MS and LC-IT/TOF-MS

Abstract

Lacosamide, a new type of antiepileptic drug, was subjected to forced degradation under the conditions of hydrolysis (acidic and alkaline), oxidation, dry heat, and photolysis to characterize its possible degradation products. The drug showed significant degradation under acidic, alkaline and oxidative conditions. The degradation products were separated on an Agilent Zorbax SB-C 18 column with gradient elution using a mobile phase consisting of acetonitrile and ammonium acetate (0.002 mol/L) with formic acid as additive. A combination of liquid chromatography hybrid triple quadrupole-linear ion trap mass spectrometry (LC-QqLIT-MS) and liquid chromatography hybrid ion trap/time-of-flight mass spectrometry (LC-IT/TOF-MS) was used to identify degradation products. A total of 7 products including 4 novel degradation products were characterized. The mechanisms of degradation products of lacosamide were discussed. Application of the method to study degradation products of lacosamide provided fragment information, allowing further investigation of the degradation pathways and intrinsic stability of the drug.

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“…The efforts have been done to quantify lacosamide by highperformance liquid chromatography (HPLC) method from rat plasma 5 , canine serum 6 , human plasma 7 , and human serum 8 . The hyphenated techniques were also available to quantify lacosamide, such as liquid chromatography-mass spectrometry (LC-MS) from human plasma, saliva, and urine sample 9 , gas chromatography-mass spectrometry (GC-MS) from human plasma 10 , and liquid chromatography-tandem mass spectrometry (LC-MS/MS) from rat plasma 11 , human serum [12][13] , post-mortem blood, serum and plasma 14 , Invitro metabolism study in human liver microsomes 15 as well as in aqueous samples [16][17][18] .…”