Lasmiditan Hemisuccinate: Selective Separation and Validation of Process Related Impurities by HPLC

Abstract

Abstract A rapid and efficient gradient RP-HPLC method was developed for the selective separation and determination of process related impurities of Lasmiditan Hemisuccinate (LDT) and its degradation products in bulk drugs. Chromatographic separation of five process related impurities of LDT was tested on Eclipse XDB C8, Primasil C18, Inertsil ODS 3V, and Zorbax SB-phenyl columns for efficient separation. A mobile phase consisting of dipotassium hydrogen phosphate buffer (20 mM, pH 7.2) and methanol was eluted in a gradient mode and monitored with a UV/PDA detector at 260 nm. Forced degradation studies were conducted on LDT to evaluate its stability under various conditions. The drug was found to be stable under neutral, thermal, and photolytic degradation conditions, while unstable in acidic, alkaline, and peroxide conditions. Chromatographic separation and identification of LDT degradation products were carried out using LC-MS. Chromatographic separation of the degradation products was achieved on Intersil ODS 3V C18 column using gradient elution, with a mixture of phosphate buffer (20 mM, pH 7.2) and methanol as mobile phase. The developed method was validated for specificity, linearity, accuracy, precision, and robustness according to ICH guidelines and can be used in quality control to determine the impurities of LDT and evaluate its stability.