Chemometrics supported optimization of a multi-attribute monitoring liquid chromatographic method for estimation of palbociclib in its dosage form: Application to a new regulatory paradigm

Abstract

The objective of present work was to develop a validated liquid chromatographic method for the estimation of palbociclib in its solid dosage forms by employing a new systematic concept. Risk assessment and control measures were undertaken along with chemometrics assistance to establish the robust method performance for studied analytical attributes viz. analyte retention, resolution, plate number, and tailing factor. Methanol %, flow rate, and pH were found influential on the performance of studied analytical attributes and optimized using a Box-Behnken experimental design. Monte-Carlo simulation was performed to evaluate the performance of the analytical procedure. A multi-attribute monitoring liquid chromatographic method employing methanol: 0.01M KH2PO4 buffer of pH 3.5 (70:30, v/v) was used with a reversed-phase column. Flow rate at 1.2mL/min and detection at 265nm monitored peak responses. The method efficiently separated analyte from the internal standard caffeine (resolution>16). Specificity (resolution>2.0), linearity (2-64μg/mL), accuracy (>99%) and precision (%RSD<1%) were well in accord with regulatory requirements. Further, analyte was detected at 1μg/mL and was stable over applied stress conditions. In a nutshell, the novel approach produced an accurate method for estimation of palbociclib in tablets with optimum method performance.