Development of a validated liquid chromatographic method for quantification of sorafenib tosylate in the presence of stress‐induced degradation products and in biological matrix employing analytical quality by design approach

Abstract

The current research work envisages an analytical quality by design-enabled development of a simple, rapid, sensitive, specific, robust and cost-effective stability-indicating reversed-phase high-performance liquid chromatographic method for determining stress-induced forced-degradation products of sorafenib tosylate (SFN). An Ishikawa fishbone diagram was constructed to embark upon analytical target profile and critical analytical attributes, i.e. peak area, theoretical plates, retention time and peak tailing. Factor screening using Taguchi orthogonal arrays and quality risk assessment studies carried out using failure mode effect analysis aided the selection of critical method parameters, i.e. mobile phase ratio and flow rate potentially affecting the chosen critical analytical attributes. Systematic optimization using response surface methodology of the chosen critical method parameters was carried out employing a two-factor-three-level-13-run, face-centered cubic design. A method operable design region was earmarked providing optimum method performance using numerical and graphical optimization. The optimum method employed a mobile phase composition consisting of acetonitrile and water (containing orthophosphoric acid, pH 4.1) at 65:35 v/v at a flow rate of 0.8 mL/min with UV detection at 265 nm using a C column. Response surface methodology validation studies confirmed good efficiency and sensitivity of the developed method for analysis of SFN in mobile phase as well as in human plasma matrix. The forced degradation studies were conducted under different recommended stress conditions as per ICH Q1A (R2). Mass spectroscopy studies showed that SFN degrades in strongly acidic, alkaline and oxidative hydrolytic conditions at elevated temperature, while the drug was per se found to be photostable. Oxidative hydrolysis using 30% H O showed maximum degradation with products at retention times of 3.35, 3.65, 4.20 and 5.67 min. The absence of any significant change in the retention time of SFN and degradation products, formed under different stress conditions, ratified selectivity and specificity of the systematically developed method.

Development and validation of a UPLC-MS method for determination of atazanavir sulfate by the “analytical quality by design” approach

“…The ATP of the current method was to develop a simple, accurate, precise, robust and specific method meeting the critical quality attributes (CQAs). CQAs are the most vital parameters that, within their defined limits, ensure the quality of the method (29). The CQAs identified for the suggested UPLC-MS method development were retention time, theoretical plates and peak tailing.…”

“…LOD and LOQ. -LOD and LOQ were calculated using calibration curve data, following the formula LOD = 3.3xSD/slope and LOQ = 10xSD/slope, where SD is the standard deviation of the regression line (29,30).…”

Implementation of analytical quality‐by‐design and green analytical chemistry approaches for the development of robust and ecofriendly UHPLC analytical method for quantification of chrysin

“…A range of essentials for ATP are enumerated in Table 1. The critical analytical attributes, viz., CAAs like, peak area (i.e., measure of analyte concentration), retention time (R t , i.e., indicative of To develop a quality method retention of the analyte), and theoretical plate count (i.e., index of column efficiency) and tailing factor (i.e., coefficient of peak symmetry) were identified so as to achieve the desired target profile [19,26,27].…”

“…Various concentrations of CHN ranging between 0.1 and 50 µg/mL using standard method of preparation and were subsequently analyzed in triplicate [19]. Least square linear regression was employed to analyze the linearity of obtained data and respective residuals curve was constructed by comparing the predicted responses with the observed ones via Microsoft-Excel spreadsheet (Washington, USA).…”

“…Use of AQbD approach is well-documented to facilitate understanding and controlling the sources of variability of the analytical procedures throughout the analytical method lifecycle, has been accentuated in the said Final Concept Paper of ICH Q14 guidance [17,18]. Application of modern and systematic principles of AQbD to analytical method development, accordingly, has been gaining vast global recognition in the pharmaceutical circles [19][20][21]. AQbD helps in embarking upon a multidimensional analytical design space (ADS) or method operable design region (MODR), which further aids in easier and smoother method transfer operations in industrial milieu [19,20,[22][23][24][25].…”