QbD-driven development and validation of an efficient bioanalytical UPLC method for estimation of olmesartan medoxomil

ABSTRACT

The present studies describe quality by design-based development of bioanalytical ultra performance liquid chromatography method of olmesartan medoxomil. Initially, method objectives were defined and critical analytical attributes (CAAs) earmarked. Method optimization was conducted using a central composite design for optimizing mobile phase ratio and injection volume as the critical method parameters (CMPs) identified from risk assessment and factor screening studies, and evaluated for their influence on peak area, theoretical plates, and asymmetry factor as CAAs. Chromatographic separation was achieved using acetonitrile:water solvent system containing 0.1% orthophosphoric acid (54:46, v/v) as the mobile phase with UV detection at 243 nm. Further optimization of bioanalytical extraction process was accomplished using a Box–Behnken design selecting extraction time, centrifugation speed, and centrifugation time as the CMPs identified from failure mode and effect analysis, and evaluated for percent recovery, peak asymmetry, and theoretical plate count as the CAAs. Establishment of calibration curve indicated linearity between concentration range of 100 and 800 ng mL⁻¹, excellent accuracy and precision with limit of detection and limit of quantification as 6.2 and 19.0 ng mL⁻¹, respectively. Drug stability studies indicated mean percent recovery ranging between 92.4 and 97.3% under various stress conditions.

GRAPHICAL ABSTRACT

KEYWORDS:

• Analytical method validation
• design of experiments
• extraction
• percent recovery
• quality risk management
• sample preparation

Conflict of Interest

The authors declare no conflict of interest.