It is clear from the literature that there are only a few methods reported with limitations of sophisticated instruments and poor sensitivity for the assay of Brivaracetam, and, particularly, no report on the simultaneous determination of the assay of Brivaracetam and its enantiomers (En) and diastereomers (DS) in a single method. Hence, it was our goal to build on a robust high-performance liquid chromatography (HPLC) process to the simultaneous assessment of Brivaracetam, and its En and DS, from the Brivaracetam drug. Accordingly, the reverse-phase chiral HPLC method development was established in a constructive way, such as buffer selection, column selection, mobile phase composition, organic modifier compositions, and column temperature variation. As a consequence, the simultaneous assessments were achieved in Daicel CHIRALPAK IG-3 (250 mm x 4.6 mm x 3 µm) with reverse-phase setup conditions consisting of 10 mM (NH4 )HCO3 buffer: CH3 CN (1:1) %v/v in an isocratic elution. High sensitivity was obtained for Brivaracetam and its stereoisomers at Limit of quantitation (LOQ) 0.25 µg/ml and Limit of detection (LOD) 0.08 µg/ml. This method is systematically validated by the International Council for Harmonization procedures. Thus, the method is applicable in quality control, in drug analysis, and in the investigation of counterfeit drugs as well.
Key words: RP chiral HPLC, Brivaracetam, Diastereomers, Enantiomer separation, Method development and validation.
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