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

Abstract

A simple and rapid stability-indicating method for determination of nintedanib (NTB) in bulk drug using HPTLC and LC-MS n 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/MS n .

A stability indicating method development and validation of a rapid and sensitive RP-HPLC method for Nintedanib and its application in quantification of nanostructured lipid carriers

“…5 Pasquini et al have reported a quality by design (QbD) based LC-MS method for estimating NTB and its impurities in soft gelatin capsules. 6 Several investigators have reported various methods like RP-UPLC, 7 LC-MS, 8 RP-HPLC in formulation, and determination of NTB and its stress degradation, 9 and which help in estimating the NTB. Some of the methods also reported degradation pathways and the degradation nature of NTB in various solvents with time.…”

“… 9 , 10 The method is precise, rapid, simple and accurate to estimate NTB as per ICH Q2 (R1) guidelines. 8 The developed method is used to quantify NTB in Nanostructured lipid carriers (NLCs) loaded with NTB. NLCs are the modified form of solid lipid nanoparticles.…”