Abstract
A rapid and highly sensitive ultra-performance liquid chromatographic (UPLC) method was developed for analysis of docetaxel trihydrate in human plasma employing the analytical Quality by Design (QbD) approach. The quality target method profile (QTMP) was defined and critical analytical attributes (CAAs) earmarked. Unlike the chromatographic methods reported in literature including the official compendiums focusing on selecting buffer species as mobile phase mixture, acetonitrile and water (60:40 %v/v) was explored as the simpler solvent system along with rational understanding of the method performance through systematic approaches. Risk assessment and factor screening studies helped in identifying mobile phase ratio and injection volume as the critical method parameters (CMPs), followed by method optimization employing face-centred cubic design (FCCD). Search for optimum chromatographic conditions was carried out through numerical desirability function and graphical optimization. Method validation studies were also performed indicating high linearity, accuracy, precision, sensitivity of the method, along with adequate stability of the docetaxel trihydrate in human plasma. The studies successfully demonstrate the utility of analytical QbD approach for the development of a novel and validated bioanalytical method for estimation of docetaxel trihydrate in human plasma with enhanced method performance.
Keywords: Design of Experiments, detection limit, linearity range, method validation, Quality by Design, risk assessment.
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