Direct separation of captopril diastereoisomers including their rotationalisomers by RP-LC using a teicoplanin column

A direct reversed-phase liquid chromatography (LC) method has been develope d for the separation and analysis of captopril and its 2R,2S diastereoisome r using a teicoplanin stationary phase. The proline containing diastereoiso mers, which are known to form conformers in aqueous solution, were also sep arated from their rotational isomers. The influence of temperature, differe nt organic modifiers and buffer type, concentration and pH were optimised t o obtain a working resolution between the two diastereoisomers and their re spective rotational isomers. The diastereoisomeric purity of several commer cial captopril batches was subsequently evaluated using a 0.05% triethylamm onium acetate (TEAA) buffer (pH 3.8) run at 1.0 ml/min with mobile phase re servoir and column temperature controlled at 0 degreesC. Throughout the stu dy online UV diode array and mass spectrometry detection was carried out si multaneously to confirm that peaks eluting from the teicoplanin column were in fact captopril and not its readily converted disulphide dimer. Addition ally, as a result of the greater detection sensitivity of mass spectrometry , it also facilitated a more accurate optimisation study where trace amount s of the rotational isomers were found to be present in the baseline at tem peratures higher than optimum. (C) 2001 Elsevier Science B.V. All rights re served.