In this application brief, we investigate the effect of these novel hybrid barrier surface technologies on metal insensitive compounds. Gefitinib (Iressa) was chosen as a candidate molecule for this study. Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor and is indicated in non-small cell lung cancer (NSCLC) and certain breast cancer patients. There are no known reports of metal sensitivity exhibited by Gefitinib, however previous reported bioanalytical methods for this compound have all employed buffers in the mobile phase to improve chromatographic peak shape. Here, we show that using ACQUITY PREMIER and MaxPeak HPS Columns improves the robustness and reproducibility for bioanalysis of gefitinib.