Quality-by-design-based ultra high performance liquid chromatography related substances method development by establishing the proficient design space for sumatriptan and naproxen combination

Abstract

Quality-by-design-based methods hold greater level of confidence for variations and greater success in method transfer. A quality-by-design-based ultra high performance liquid chromatography method was developed for the simultaneous assay of sumatriptan and naproxen along with their related substances. The first screening was performed by fractional factorial design comprising 44 experiments for reversed-phase stationary phases, pH, and organic modifiers. The results of screening design experiments suggested phenyl hexyl column and acetonitrile were the best combination. The method was further optimized for flow rate, temperature, and gradient time by experimental design of 20 experiments and the knowledge space was generated for effect of variable on response (number of peaks ≥ 1.50 - resolution). Proficient design space was generated from knowledge space by applying Monte Carlo simulation to successfully integrate quantitative robustness metrics during optimization stage itself. The final method provided the robust performance which was verified and validated. Final conditions comprised Waters® Acquity phenyl hexyl column with gradient elution using ammonium acetate (pH 4.12, 0.02 M) buffer and acetonitrile at 0.355 mL/min flow rate and 30°C. The developed method separates all 13 analytes within a 15 min run time with fewer experiments compared to the traditional quality-by-testing approach.

Application of capability indices and control charts in the analytical method control strategy

“…Thus, capability indices can help to decide whether the analytical method is only able to provide enough conforming results to check if a method is fit for its intended purpose . Various examples of the usefulness of capability indices in the framework of analytical method validation can be found in the literature .…”

Development of an ultra high performance liquid chromatography method for determining triamcinolone acetonide in hydrogels using the design of experiments/design space strategy in combination with process capability index

“…However, one of the main problems is to select the experimental design because not all statistical designs have the same ability to identify which factors are important and to quantify the effect of each variable . The Plackett and Burman, Box–Behnken, Doehlert, principal component analysis, or central composite designs are some widely used examples .…”

“…Another key component of QbD is to specify the design space (DS) of analytical methods where quality assurance is provided . Today, different commercial software dedicated to method development is on the market based on the linear solvent strength (LSS) theory and DOE and MLR as alternatives to LSS.…”

“…Fusion AE commercial software (S‐Matrix, Eureka, CA, USA) applied the DOE/MLR strategy allowing computation and modeling of robustness using the process capability index Cp as criterion. To compute Cp, the software needs the maximum expected variations of the input parameters and the tolerance limits on the responses, all must be established by the user . With all this information, the software can define the DS of the analytical method.…”

Automated statistical experimental design approach for rapid separation of coenzyme Q10 and identification of its biotechnological process related impurities using UHPLC and UHPLC–APCI‐MS

“…DS can be generated by the simultaneous study of all chromatographic critical process parameters such as gradient time, column oven temperature, flow rate, pH of mobile phase, etc. by using Designs of Experiments (DoE) [26][27][28][29][30][31][32][33][34]. Finally, the in silico toxicity of the characterized impurities was predicted using TOPKAT (toxicity prediction by computer-assisted technology) and DEREK (deductive estimate of risk from existing knowledge) software [35][36][37].…”