Non-linear standard calibration curves occur frequently in liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS), necessitating the use of non-linear regression curve fitting or a reduction in assay dynamic range. Non-linearity can be minimized by the use of stable isotope internal standards, if the cause of curve bending is ionization saturation. Unfortunately, stable isotope internal standards can be difficult or expensive to synthesize. Structural analog internal standards, if sufficiently close to analytes both in chemical structures and HPLC retention times, may mimic the effect of stable isotope internal standards. Tentative experimental evidence supporting this concept is presented in this paper. Copyright © 2002 John Wiley & Sons, Ltd.