Background: The fixed-dose combination of vildagliptin (VDG) and dapagliflozin (DGZ) is used in the treatment of type 2 diabetes mellitus. According to the literature survey, RP-HPLC and HPTLC methods have been reported for routine analysis of VDG and DGZ. These chromatographic methods have been developed using potentially neurotoxic and teratogenic solvents, which are unsafe for human and aquatic animal life and hazardous to the environment. These types of organic solvents shall be replaced or reduced during chromatographic analysis of drugs for the safety of human and aquatic animal life and the protection of the environment. The novel white analytical chemistry (WAC) approach has been introduced, which emphasizes robust, green, user-friendly, economical, and rapid analysis of drug samples. Objective: Hence, the WAC-based RP-HPLC method has been developed for the estimation of VDG and DGZ using lower toxic and economical solvents. Method: The development of the RP-HPLC method includes the implementation of the analytical quality by design approach using principles of design of experiments to reduce organic waste generation and regulatory compliance of analytical method. The central composite design was applied for response surface modeling (RSM) and optimization of the RP-HPLC method. The method validation was carried out according to ICH Q2 (R1) guidelines. Results: The fixed-dose combinations of VDG and DGZ were assayed, and results were found in compliance with their labeled claim. The published and proposed RP-HPLC methods were assessed for chromatographic analysis of VDG and DGZ using the Red-Green-Blue (RGB) model, AGREE calculator, Eco-Scale Assessment tool, GAPI software, and NEMI standards. Conclusions: The proposed method was found to be robust, green, economical, and user-friendly for chromatographic analysis of VDG and DGZ. The proposed method can be an economical and eco-friendly analytical tool in the pharmaceutical industry for quality control and routine analysis of fixed-dose combinations of VDG and DGZ. Highlights: Hybrid principles of WAC and analytical quality by design to RP-HPLC method for simultaneous estimation of VDG and DGZ in their fixed-dose combinations.

Background: A combination of pioglitazone hydrochloride with teneligliptin hydrobromide hydrate is used to treat type-2 diabetes. Several chromatographic techniques have been described in the literature for determination of each of these medications separately. But these procedures used organic solvents that could be dangerous for humans and animals, not to mention harmful to the environment. It is vital to substitute or reduce the use of these neurotoxic and teratogenic solvents in the chromatographic analysis of these anti-diabetic medications to ensure the safety of life and safeguard the environment. The chromatographic technique used for sample analysis should have characteristics like robustness, eco-friendliness, cost-effectiveness, and user-friendliness following the recently developed idea of white analytical chemistry. Teneligliptin and pioglitazone have not yet been simultaneously estimated using a chromatographic method that has been documented in the literature. Methods: A white analytical chemistry-assisted RP-HPLC method has been developed to fill this gap, using economical and eco-friendly solvents. The design of the experiment approach was used during the development of the RP-HPLC method to reduce organic waste and guarantee that the procedure complied with all applicable regulations. Response surface models were built using the full factorial design approach, and the analytical design space was investigated. This method allowed for the identification of an optimal chromatographic condition within the method's operational design region, allowing reliable RP-HPLC analysis of pioglitazone and teneligliptin. Results: The developed RP-HPLC technique underwent validation and was used effectively to assess these drugs in their fixed-dose combinations. Assessments were made of the suggested and published RP-HPLC techniques' validation status, process greenness, cost, and analysis time. For a thorough examination, this review included white analytical chemistry-based RGB models and different green analytical chemistry-based tools. Conclusion: In allowing the simultaneous estimate of teneligliptin and pioglitazone, the devised approach demonstrated robustness, eco-friendliness, and cost-effectiveness.

According to current concepts of white analytical chemistry (WAC), the use of organic solvents those are teratogenic and carcinogenic must be avoided for the protection of the environment and of the analysts. This led to the development and validation of the WAC–assisted green liquid chromatographic technique (reverse-phase high-pressure liquid chromatography (RP-HPLC)) for the simultaneous analysis of anti-hypertensive drugs (azilsartan medoxomil, chlorthalidone and cilnidipine) in human plasma and their fixed-dose combinations. The analytical quality by design approach was used in conjunction with the design of experiments and chemometrics concepts to develop the method. To develop the green RP-HPLC method, critical method variables (CMVs) and critical analytical attributes were identified using the multivariate analytical tools principal component analysis and partial least square regression. Using the Box–Behnken design, the design of experiments was used for CMV optimization and response surface analysis. It was possible to explore the analytical design space for the life cycle management of the RP-HPLC method. The developed method was found to be validated following International Council for Harmonization Q2 (R1) and M10 requirements. Using the red, green and blue paradigm, the existing and proposed chromatographic methods were evaluated for their validation efficacy, greenness profile and cost-effectiveness.

Background: Bosutinib is a small-molecule BCR-ABL and Src tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia. According to published literature, no stability-indicating reversed-phase (RP)-HPLC method has been reported for the estimation of bosutinib. Objective: A stability-indicating RP-HPLC method has been developed for the stability study of bosutinib, using a risk- and design of experiments (DoE)-based enhanced analytical quality by design (AQbD) approach. Method: The risk-based AQbD approach was applied by risk parameter identification and risk assessment by risk priority number (RPN) ranking and filtering, as per International Conference on Harmonization (ICH) Q9 guidelines. The DoE-based AQbD approach was implemented by response surface analysis using a central composite design. The risks of critical method risk parameters were mitigated by navigation of design space and framing of control strategy. Results: Chromatographic separation was performed using a C18 column and acetonitrile–1.0% triethylamine (v/v) in water (pH 7.0, adjusted by ortho-phosphoric acid). The developed method was validated according to ICH Q2 (R1). The developed and validated method was applied for the assay of bosutinib in pharmaceutical dosage forms. The developed method was extended for an oxidative degradation kinetic study of bosutinib at different pH conditions. Conclusions: The developed RP-HPLC method can be used as an analytical tool for quality control and stability studies of pharmaceutical dosage forms of bosutinib in the pharmaceutical industry. Highlights: The development and validation of a stability-indicating RP-HPLC method for the estimation of bosutinib by implementation of a DoE- and risk-based enhanced AQbD approach. The method was applied to assay pharmaceutical dosage forms and in an oxidative degradation kinetic study.