VALIDATED STABILITY- INDICATING HPTLC METHOD FOR NINTEDANIB & CHARACTERIZATION OF DEGRADANTS BY LC-MSⁿ

A simple and rapid stability-indicating method for determination of nintedanib (NTB) in bulk drug using HPTLC and LC-MSⁿ was developed and validated. Stress degradation studies were carried out by hydrolysis, oxidation, thermal and photolytic. Drug was found to be stable in thermal whereas one degradant was found in acid hydrolysis, three in basic hydrolysis, five in oxidative and two in photolytic stress. The probable structures of the degradation products were predicted & the degradation pathway was also established. Chromatography was carried out using silica gel 60 F₂₅₄ TLC plate and mobile phase of Chloroform : Methanol in the ratio 7:3 v/v. The densitometric determination was done at 386 nm. The degradants were not detectable when stressed as per ICH recommended conditions but on increasing the strength of acid, base and peroxide, the degradants were very much prominent and were easily detectable in HPTLC. The LC system consisted of a Zorbax Bonus C₁₈ (150 mm×4.6 mm, 3.5 µ). A gradient mobile phase consisting of mobile phase A: 10mM Ammonium formate (0.05% formic acid): ACN (pH 3.9) (90:10) and mobile phase B: 10mM Ammonium formate (0.05% formic acid): ACN (pH 3.9) (10:90) with a flow rate of 0.7mL/min was used to separate the degradants up to a total retention time of 15 min. Mass spectrometric detection was performed using Thermo Scientific LCQ fleet Ion Trap LC/MSⁿ.