Quality by design-assisted development of a capillary electrophoresis method for the enantiomeric purity determination of tenofovir.

Abstract

A CE method was developed and validated for the assessment of the chiral purity of the drug tenofovir applying a quality by design approach. Following selection of a quaternary ammonium β-CD as chiral selector, a fractional factorial resolution V+ design was employed for identification of the critical process parameters, while a central composite design served for method optimization. The final method used a 40/50.2cm, 50μm id fused-silica capillary, a BGE composed of a 100mM sodium phosphate buffer, pH 6.4, containing 45mg/mL quaternary ammonium β-CD, an applied voltage of 18kV, and a capillary temperature of 22°C. Robustness was assessed by a Plackett-Burman design. The method was validated according to guideline Q2(R1) of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and enabled the determination of the (S)-enantiomer of tenofovir at the 0.1% level.