Although the isoniazid (INH) has been the most widely used antituberculostatic prodrug due to its high efficacy, problems of microbial resistance are frequently observed[1]. In this context, its complexation with transition metal (Fe) could be used in order to overcome this drug limitation. In fact, the use of the pentacyanidoferrate(II)-INH complex (PCF-INH) has demonstrated to be effective in inhibiting resistant strains of Mycobacterium tuberculosis; however, the mechanism which involves the transformation of INH into isonicotinoyl radical is not completely understood yet[2] . Once the PCF-INH complex needs to be transported in different organic systems until it achieves lung, stability studies in different salt-rich aqueous media were performed (phosphate buffered saline-PBS and PBS/trichloroacetic acid-TAA ). The TAA was used to simulate more acid regions (e.g. stomach). In addition to assays with the PCFINH, a Prussian blue derivate containing INH (PB-INH) was also considered. Results showed INH oxidation and isonicotinate (ISN) formation in both solutions (Fig. 1a-b). For the PCF-INH, INH can be changed for H2O in coordination sphere. This complex can be oxidized[3] and then reacting with PCF-INH and free INH, resulting in PCFISN and ISN formation, respectively. PCF-ISN also can changes ISN ligand for H2O, releasing ISN to solution (Fig. 1c). In PB-INH complex, phosphate ions from PBS solutions reacts with Fe(III), breaking PB-INH structure, forming PCF-INH. Fe(III), in excess, can easily oxide free INH and PCF-INH, resulting in ISN and PCF-ISN formation, even in TAA presence (Fig. 1d). Taking together, these results demonstrate that salt-rich buffering medium (neutral and acid) can provide isonicotinoyl radical (and then ISN) by INH oxidation.