The solvent dependency of the detection response is one of the major limitations of corona-charged aerosol detector (C-CAD). The present study provides an empirical investigation of the utility of temperature and flow rate gradient to overcome the solvent gradient limitation of C-CAD. By means of a flow injection study we have demonstrated that the response of C-CAD remains relatively unaltered with flow rate variation, when used with water-rich eluents. Based on these findings two separation approaches were developed and their utility for C-CAD response normalisation demonstrated using a mixture of 8 analytes. In the first approach a solvent gradient is avoided by performing the separation using a temperature gradient under isocratic conditions. A second approach uses flow rate programming to improve the speed of isocratic temperature gradient separations. To counteract the reduction in detection response resulting from the water-rich eluent, a secondary stream of pure acetonitrile was mixed with the column effluent, which yielded 3-fold increase in detection response. The latter approach involved simultaneous variation in the flow rate and column temperature and reduced the separation time by 30%, with the response homogeneity comparable to that of the former approach. Lastly, an inverse-gradient solvent compensation approach was used to evaluate the response homogeneity and the applicability of the above approaches for quantitative analysis. Both the approaches produced good peak area reproducibility (RSD% < 15%) and linearity (R2 >0.994, on log-scale) over the sample mass range of 0.1-10µg. The response deviation across the mixture of 8 compounds at 7 concentration levels was 6-13% compared to 21-39% in solvent gradient and was comparable to the inverse gradient solvent compensation approach. Finally, the applicability of these approaches for typical impurity profiling was demonstrated at a concentration of 5µg/mL (0.1% of the principal compound).