Characterization of Forced Degradation Products & Related Substances of Bilastine by Online LC-Q-TOF-MS and In-silico Study of Characterized Compounds

Abstract

This manuscript is about the identification of degradation products and four related substances of a novel antihistaminic drug Bilastine by LC-Q-TOF-MS/MS. A selective stability-indicating RP-HPLC method was developed for the separation of Bilastine, its 4 related substances and degradation products. Separation was done through Inertsil ODS-3® column (150 x 4.6 mm, 5 µm) using 10 mM ammonium acetate (pH 6.00) and methanol as eluent in a gradient at 1.0 mL/min flow rate. The chromatogram was extracted at 275 nm wavelength. Two degradation products and four related substances were identified and their structures were proposed on the basis of data obtained from LC-Q-TOF-MS/MS experiments. The developed method was validated in accordance with ICH Q2 and USP <1225> guidelines and it was found to be specific, precise, accurate and robust for the intended use. The method was linear in the range of 160-240 µg/mL for drug and 1.15-4.5 µg/mL for related substances with R2 value greater than 0.999 and 0.997 for drug and RS respectively. Percentage of relative standard deviation for validated parameters was less than 2. Structures of the drug, its degradation products and related substances were subjected to in silico studies for prediction of physicochemical, pharmacokinetic and toxicological properties with the help of QikProp module of Schrödinger suite 2017-1 software. Predicted in silico values suggested that they are safe and lie within the recommended range of parameters.