Evaluation of a Mixed Micellar Electrokinetic Capillary Electrophoresis Method for Validated Pharmaceutical Quality Control

摘要

A stability indicating, quality control analysis method was developed for VASOTEC, an antihypertensive drug. Mixed micellar capillary electrokinetic electrophoresis employing the anionic detergent, sodium lauryl sulfate (SDS), and the nonionic detergent, Brij 35, was used to separate enalapril maleate (EM), the active component of VASOTEC, and its degradates, the enalapril diketopiperazine (DKP) and enalaprilat (DA). The formation of easily separable rotary isomers by EM required that the capillary temperature be maintained at 50°C except in the presence of Brij 35. Adjusting the Brij 35 concentration allowed manipulation of selectivity for the neutral DKP degradate with respect to EM and DA. Detection sensitivity was enhanced ten-fold to 0.1 ug/mg by utilizing a 100 micron I.D. rather than a 75 micron I.D. capillary. Theoretical plates were determined to be 71,000 plates/m for the active component or 70 times that for the HPLC method. Critical factors in method stability were pH, temperature and applied voltage. Concentrations of SDS, Brij 3 5 and sodium borate could be varied ±5% without significant effects on the separation. Capillary electrophoresis was determined to be potentially useful for drug quality control analysis because of its resolution, speed, capillary longevity and versatility, low solvent consumption, long term expense, and simplicity of training and operation.