With this study, we investigated why some small molecules demonstrate narrow dynamic ranges in electrospray ionization-mass spectrometry (ESI-MS) and sought to establish conditions under which the dynamic range could be extended. Working curves were compared for eight flavonoids and two alkaloids using ESI, atmospheric pressure chemical ionization (APCI), and heated electrospray ionization (HESI) sources. Relative to reserpine, the flavonoids exhibited narrower linear dynamic ranges with ESI-MS, primarily due to saturation in response at relatively low concentrations. Saturation was overcome by switching from ESI to APCI, and our experiments utilizing a combination HESI/APCI source suggest that this is due in part to the ability of APCI to protonate neutral quercetin molecules in the gas phase. Thermodynamic equilibrium calculations indicate that quercetin should be fully protonated in solution, and thus, it appears that some factor inherent in the ESI process favors the formation of neutral quercetin at high concentration. The flavonoid saturation concentration was increased with HESI as compared to ESI, suggesting that inefficient transfer of ions to the gas phase can also contribute to saturation in ESI-MS response. In support of this conclusion, increasing auxiliary gas pressure or switching to a more volatile spray solvent also increased the ESI dynamic range. Among the sources investigated herein, the HESI source achieved the best analytical performance (widest linear dynamic range, lowest LOD), but the APCI source was less subject to saturation in response at high concentration.