LC, LC-MS/MS STUDIES FOR IDENTIFICATION AND CHARACTERIZATION OF DEGRADATION PRODUCTS OF LAMOTRIGINE AND ESTABLISHMENT OF MECHANISTIC APPROACH TOWARDS DEGRADATION

Abstract

The objective of present investigation was to separate, identify, and characterize the degradation products of lamotrigine under hydrolytic, oxidative, photolytic, and thermal stress conditions as per International Conference on Harmonization (ICH) guideline Q1A (R2). The drug underwent degradation under acidic, basic, and oxidative stress, while it was stable in photolytic and thermal stress conditions. A total four degradation products were formed which were separated by using HPLC on C18 column using gradient elution program. A complete mass fragmentation pattern of the drug was first established with the help of LC-MS/MS studies. The stressed samples were subjected to LC-MS/MS studies. The obtained mass spectral data were employed to characterize three degradation products and assign structures. Complete information was used to establish the degradation pathway of the drug. The degradation products were identified as 3-amino-6-(2, 3-dichlorophenyl)-1, 2, 4-triazin-5(4H)-one, 6-(2, 3-Dichloro-phenyl)-2-oxy-[1, 2, 4] triazine-3, 5-diamine, 6-(2, 3-Dichloro-phenyl)-4-oxy-[1, 2, 4] triazine-3, 5-diamine.

Keywords:

• degradation pathway
• lamotrigine
• LC-MSMS
• stability indicating method
• stress studies
• triazine

ACKNOWLEDGMENT

Authors wish to thank DBT-ICT Center for Energy Biosciences, Mumbai for conducting LC-MS/MS studies.