Because of CO's known endogenous signaling roles and its demonstrated pharmacological activity at low and safe concentrations, there is considerable interest in chemical strategies that allows for generation of carbon monoxide from organic molecules under near-physiological conditions. Along this line, we report our work on studying the ability of iron porphyrin to catalyze CO generation from phenylpyruvic acid (PPA). To utilize this system for potential CO therapeutics and diagnostic applications, an activated charcoal formulation was designed, optimized, and assessed. Among the various iron porphyrin analogs studied, tetrakis(pentafluorophenyl)porphyrin iron (III) (TPFP) immobilized on activated charcoal was found to produce up to 60% CO from PPA. This chemistry could also be utilized in PKU diagnostics for quantification of PPA accumulation in urine. This catalytic conversion allows for the use of CO generation to rapidly quantify PPA concentration in urine samples. Another potential relevance of this CO generation pathway is the extent to which it could undergo in vivo as an endogenous source of CO.