Development, stability‐indicating assessment, and evaluation of influential method conditions using a full factorial design for the determination of Nintedanib esylate‐related impurities

Abstract

The design of an appropriate analytical method for assessing the quality of pharmaceuticals requires a deep understanding of science, and risk evaluation approaches are appreciated. The current study discusses how a related substance method was developed for Nintedanib esylate. The best possible separation between the critical peak pairs was achieved using an X-Select charged surface hybrid Phenyl Hexyl (150 × 4.6) mm, 3.5 μm column. A mixture of water, acetonitrile, and methanol in mobile phase-A (70:20:10) and mobile phase-B (20:70:10), with 0.1% trifluoroacetic acid and 0.05% formic acid in both eluents. The set flow rate, wavelength, and injection volumes were 1.0 ml/min, 285 nm, and 5 μl, respectively, with gradient elution. The method conditions were validated as per regulatory requirements and United States Pharmacopeia general chapter < 1225 >. The correlation coefficient for all impurities from the linearity experiment was found to be > 0.999. The % relative standard deviation from the precision experiments ranged from 0.4 to 3.6. The mean %recovery from the accuracy study ranged from 92.5 to 106.5. Demonstrated the power of the stabilityindicating method through degradation studies; the active drug component is more vulnerable to oxidation than other conditions. Final method conditions were further evaluated using a full-factorial design. The robust method conditions were identified using the graphical optimization from the design space.

Stability‐indicating method for quantification of potential genotoxic impurity and other organic impurities of chlorzoxazone using hyphenated techniques

“…Both methods were developed and validated considering the International Council for Harmonization (ICH) requirements, which met its acceptance criteria and were found to be specific, linear, accurate, precise, and robust [24][25][26][27][28]. The results of the forced degradation study confirmed that the developed RP-HPLC-UV method is stabilityindicating, in addition to being specific and selective in the separation and quantitative determination of organicrelated impurities of chlorzoxazone drug substance and drug product [29,30].…”