A pressure-assisted capillary zone electrophoresis method was developed to determine the pKa values of a triptolide derivative (LLDT-246) and its impurities. The method was performed in an uncoated fused-silica capillary under the electric voltage of 18 kV and 50 mbar of external pressure applied simultaneously. A series of running electrolyte buffers were used with pH ranging between 2.2 and 10.0 with the constant ionic strength of 0.05 M. The values of pKa of LLDT-246 and two impurities were calculated based on the pH dependence of effective mobilities (μeff). The pKa value of LLDT-246 was in good agreement with that of determined by potentiometric titration method.