An HPLC method for the determination of iron, zinc, and copper in tissue samples has been developed utilizing a photo-diode array detection system. The method relies upon acid digestion of the samples to free the metals from the sample matrix followed by pre-column derivatization with a common complexometric indicator. With extremely small amounts of sample available for some applications, a solid-phase extraction of the complexed metal ions can be included in the sample work-up to ensure measurable concentrations of the metal complexes are obtained for analysis.