Capillary Electrophoresis Method for the Chiral Purity Determination of Pregabalin Derivatized with Dansyl Chloride
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A capillary electrophoresis method for the determination of the chiral purity of pregabalin upon derivatization with dansyl chloride was developed using design of experiment methodologies. A D-optimal design was used for the identification of the critical process parameters, while a central composite face centered design and Monte Carlo simulations were employed for defining the design space of the method. Final working conditions consisted of a background electrolyte composed of a 100 mM sodium phosphate buffer, pH 2.5, containing 40 mg mL−1 heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, a separation voltage of 15 kV and a capillary temperature of 25 °C. The analyses were carried out in a 40/50.2 cm fused-silica capillary with an inner diameter of 50 µm. Upon testing the robustness using a Plackett–Burman design, the method was validated according to the International Council on Harmonization guideline Q2(R1). The method allowed the detection of the (R)-enantiomer at the 0.015% level with a limit of quantitation at the 0.05% level with regard to a sample containing 1.59 mg mL−1 pregabalin. The method was subsequently applied to the determination of the stereochemical purity of the drug in commercial capsules.
KeywordsPregabalin Enantiomeric purity Stereoisomer analysis Capillary electrophoresis Quality by design
The gift of pregabalin and the racemic drug by Optimus Drugs PVT Ltd. (Hyderabad, India) is gratefully acknowledged.
Compliance with Ethical Standards
Conflict of interest
The authors have declared no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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