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

Abstract

Dexmedetomidine is a selective α2 -adrenergic agonist used for patient sedation, while its enantiomer levomedetomidine has no sedative effects. As CE has been shown to be a powerful technique for enantiomer analysis, the aim of the study was the quality by design-based development of a CE-based limit test for the enantiomeric impurity levomedetomidine. The analytical target profile was defined that the method should be able to determine levomedetomidine with acceptable precision and accuracy at the 0.1% level. From initial scouting experiments, sulfated β-cyclodextrin was selected as chiral selector. The critical process parameters were identified in a fractional factorial resolution V+ design, while a central composite face centered design and Monte Carlo simulations were used for defining the design space of the method. The selected working conditions were a 21.3/31.5 cm, 50 μm id fused-silica capillary, a 50 mM sodium phosphate buffer, pH 6.5, containing 40 mg/mL sulfated β-cyclodextrin, a capillary temperature of 17°C and an applied voltage of 10 kV. Validation according to the ICH guideline Q2(R1) demonstrated repeatability and intermediate precision of content and migration time between 9.3 and 4.2% with accuracy in the range of 92.0 and 98.9%.