Development of a Validated LC Method for Separation of Process-Related Impurities Including the R-enantiomer of S-Pramipexole on Polysaccharide Chiral Stationary Phases

摘要

Despite the availability of a few methods for individual separation of S-pramipexole from its process-related impurities, no common liquid chromatography (LC) method is reported so far in the literature. The present article describes the development of a single-run LC method for simultaneous determination of S-pramipexole and its enantiomeric and process-related impurities on a Chiralpak AD-H (150 x 4.6 mm, 5m) column using n-hexane/ethanol-butylamine (75:25:0.1 v/v/v) as a mobile phase in an isocratic mode of elution at a flow rate of 1.2 ml/min at 30 degrees C. The chromatographic eluents were monitored at a wavelength of 260 nm using a photodiode array detector. Excellent enantioseparation with good resolutions (Rs 2.88) and peak shapes (A(s) 1.21) for all analytes was achieved. The proposed method was validated according to International Conference Harmonization (ICH) guidelines in terms of accuracy, precision, sensitivity, and linearity. Limits of quantification of impurities (0.25-0.55 g/ml) indicate the highest sensitivity achievable by the proposed method. The method has an advantage of selectivity and suitability for routine determination of not only chiral impurity but also all possible related substances in active pharmaceutical ingredients of S-pramipexole. Chirality 27:430-435, 2015. (c) 2015 Wiley Periodicals, Inc.