Determination of the endothelin receptor antagonist ABT-627 and related substances by high performance liquid...

The determination of the endothelin (ET) antagonist receptor ABT-627 (I) and related substances is performed by HPLC. I is determined in bulk drug substance and drug formulation using isocratic conditions and an Inertsil ODS-2 column. The determination is stability indicating and detector response is linear from 24 to 118 microg ml(-1) (33-164% of assay level). Intermediate precision for the determination ranged from +/- 0.60 to +/- 1.9% RSD. The measurement is accurate, with quantitative recovery of I from the formulation placebo. Related substances in I and formulated I are determined using the same chromatographic conditions, with a gradient elution profile to elute impurities having varying relative polarities. The detector response for related substances determination is linear for I from 0.60 to 17.8 microg ml(-1) (0.05-1.5% of assay level) with the limit of detection and quantitation estimated at 0.01 and 0.05%, respectively. Comparable precision was obtained in drug substance and drug formulation (RSD values +/- 3.7 to +/- 12% and +/- 5.5 to 16.9%, respectively for impurities ranging from 0.05 to 0.30%). The quantitated impurities agreed well for the same lot of I when assayed as a bulk substance and after the formulation into a drug product.