The activity of platinum compounds is dependent on nucleophile substitution reactions. In this paper, we study the reactivity of L-met with carboplatin, oxaliplatin and cisplatin by following with HPLC-UV the concentration of L-met and by characterizing the resulting adducts with LC-MS. In the absence of NaCl, in water, the initial rate at which L-met concentration decreases with cisplatin, oxaliplatin and carboplatin is 0.25 90.007, 0.057 9 0.01 and 0.17 90.02 mM h -1 , respectively. In phosphate buffer this rate is 0.056 9 0.009 for cisplatin, 0.019 90.001 and 0.13 90.02 for carboplatin and oxaliplatin, respectively. Reactions of L-met with cisplatin occurred via its conversion into monoaqua species in water and into phosphato-derivatives (AP) in phosphate buffer but finally the same methionine-platinum adducts M2 [(NH 3 ) 2 (met)]Pt, M4 and M5 [(met) 2 ]Pt were characterized. Reaction of carboplatin with L-met occurred via the formation of M0 [(NH 3 ) 2 (met)(CBDCA)]Pt whose structure is consistent with the direct interaction of L-met with carboplatin. However, the same final products as those found with cisplatin were characterized. The reaction of oxaliplatin with L-met proceeded through a mechanism similar to that of carboplatin to give M7 [(met)(DACH)]Pt. In the presence of NaCl, cisplatin directly reacted with L-met to yield at least five methionine -platinum adducts. The reaction of carboplatin gave the same adducts suggesting its transformation into cisplatin. The reaction of oxaliplatin with L-met occurred via the formation of aquated species A [(OH)(Cl)(DACH)]Pt which readily underwent reaction with L-met to form M6 [(met)(Cl)(DACH)]Pt and M7. This study shows that the reactivity of cisplatin, carboplatin and oxaliplatin is dependent on the media in which they occur. The discrepancy between their reactions with L-met could partly explain their therapeutic differences.