<p>A systematic analytical method for discriminating methamphetamine (MA) from its structural analogs was developed by combining a solid-phase chromogenic method with the use of a molecularly imprinted polymer (MIP) and Simon reaction. L-proline (Pro), L-hydroxyproline (HYP), <i>N</i>-methylbenzylamine (NMe-BA), and <i>N</i>-isopropylbenzylamine (NIP-BA) were selected as false positives, while <i>tert</i>-butoxycarbonyl derivatized MA (<i>t</i>-Boc-MA) was selected as a false-negative substance. MA and the structural analogs were loaded into SupelMIP™ SPE-Amphetamines cartridges and Simon's reagent was added to the cartridge, then the coloration of the solid-phase gel was observed from outside the cartridge. After elution with a basic solution, Simon's reagent was added to the eluate (first-step eluate), and a change in color tone was observed. The MIP was then heated under acidic conditions, and the analytes were eluted (second-step eluate) with water, basified at pH 10, and the Simon reaction was repeated. Pro and HYP could be discriminated from MA by the color tone of the MIP solid-phase gel, whereas NMe-BA and NIP-BA could be discriminated from MA by the color tone of the first-step eluate. In addition, the color tone of the second-step eluate confirmed the presence of <i>t</i>-Boc-MA.</p> Graphical abstract <p></p>