RESUMO
Process impurities found in the drug substance 5-aminosalicylic acid were determined by micellar electrokinetic capillary chromatography (MECC). In order to enhance the detection of trace impurities, the parent drug was dissolved to an unusually high concentration of 5 mg/mL. To reduce the dispersive processes of electromigration dispersion and anti-stacking, both of which occur at high solute concentration, the electrolyte pH was adjusted to be close to the apparent isoelectric point (pI) of the zwitterionic drug. In this fashion, the net charge on the solute should approach zero thereby minimizing the aforementioned sources of band-broadening. Two additional developments are reported. Short sodium hydroxide washes were used to optimize the MECC reproducibility. The elimination of anti-stacking permitted the use of peak heights to quantitate low level impurities with improved precision. The method was compared to the high-performance liquid chromatographic (HPLC) method found in the United States Pharmacopoeia (USP). Both the MECC and HPLC methods were found to be similar with regard to migration-retention time reproducibility, peak area-height reproducibility, linearity and limit of quantitation. The MECC separation is 2x faster than HPLC. Both methods meet the system suitability requirements described in the USP.
