QbD-Based UPLC Method for Quantification of Brexpiprazole in Presence of Impurities

What is it about?

Quality-by-design-based UPLC method was developed for chromatographic separation to quantify the antischizophrenic drug brexpiprazole in the presence of impurities. Research findings from pHscouting studies were used as control variables which influence the chromatographic separation. The peak tailing and resolution are the response variables and established the design-space by DoEstudy for selection of suitable chromatographic conditions. Separation was achieved with lower particle size stationary phase and buffer pH 2.0 in the mobile phase. The present method developed through C18 50 × 2.1 mm, Ethylene-Bridged-Hybrid technology column with 1.7 μm particles, mobile phase consists of pH 2.0 buffer and acetonitrile (67:33 v/v), flow rate of 0.5 mL min−1 and detection wavelength at 215 nm. The retention time of brexpiprazole is 0.6 min and all impurities were eluted within 2 min. The method linearity ranges were 20.4–61.3 μg mL−1 for assay and 0.88–6.59 μg mL−1 for dissolution with correlation-coefficients of 0.9999 and 0.9998 for assay and dissolution, respectively. The recovery values were found in between 99.3 and 100.9%. The method shows stability-indicating on the basis of noninterference of placebo, and impurities from forceddegradation studies. Method validation was carried out according to ICH guideline Q2 (R1).

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Why is it important?

AQbD-approach-based reversed-phase UPLC method was developed for chromatographic separation of brexpiprazole from impurities. DoE was the basis for the establishment of design-space for systematic selection and optimization of UPLC chromatographic parameters (BEH technology column with lower particle size stationary phase with acidic pH mobile phase) were used for UPLC separation. The present study report is the first time report on the fast analysis, stability-indicating UPLC method with established design space for chromatographic separation of impurities from brexpiprazole. Sample extraction procedure from the tablet matrix was established as the brexpipazole is a BCS class 2 drug having low solubility. The method has demonstrated the robustness, linearity, range, accuracy and precision based on ICH method validation guideline i.e., ICH Q2 (R1). Noninterference of blank, placebo and impurity peaks for brexpiprazole peak from forced degradation stress studies reveal that the present method is stability-indicating. Design-space was established by DoE studies and this multivariate analysis will provide the broad knowledge on the interaction and effect of input method parameters on system suitability parameters. Present method was economic, and developed to speed up the analytical activities by significantly reducing the analysis time for the pharmaceutical industries. In addition to the quantification of brexpiprazole in bulk and finished drug product, this method can be used for estimation of drug release from a tablet in the in vitro dissolution analysis of drug product as an application. For dissolution its suitability verified for 4 mg strength and further scope for applicability to all strengths to be verified and validated.

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