A Validated Chiral LC Method for the Separation and Quantification of ( S,R,S )-Enantiomer and ( R,R,R )-Isomer of Aprepitant

摘要

A new and accurate chiral liquid chromatographic method has been developed for the separation and quantification of (S,R,S)-enantiomer (unwanted enantiomer) and (R,R,R)-isomer (key intermediate) of aprepitant in bulk drug and formulation samples of apprepitant. The elution time was approximately 20 min using an immobilized amylose-based chiral stationary phase (Chiralpak-IA). The mobile phase was n-hexane and ethanol (90:10, v/v) and was delivered at a flow rate of 1.0 mL min−1. Detection was carried out with a wavelength set to 220 nm. The resolution factor between enantiomers was found to be greater than five. Limit of detection for both (S,R,S) enantiomer and (R,R,R) isomer of aprepitant was 0.035 µg, and limit of quantification for both (S,R,S) enantiomer and (R,R,R) isomers of aprepitant was 0.1 µg, for a 10 µL injection. The developed method showed excellent linearity (r > 0.999) for both isomers. When the method was applied to bulk drug samples and in pharmaceutical formulations recoveries were obtained ranging from 97.2 to 103.1%. Aprepitant sample solutions were found to be stable when characterized over a period of 48 h.