Kinetics and Mechanism of Permanganate Oxidation of Clopidogrel Hydrogen Sulfate: An Antiplatelet Drug in Acid Perchlorate Solutions

The oxidation of clopidogrel hydrogen sulfate, commercially known as Plavix, by permanganate ion in aqueous perchloric acid medium at a constant ionic strength (I = 0.06 mol dm(-3)) has been investigated spectrophotometrically at 526 nm. The reaction between clopidogrel hydrogen sulfate and permanganate in acid medium exhibits a 5:4 stoichiometry. The identified oxidation products, 4,5,6,7-tetrahydrothieno[3,2-c]pyridine, (2-chlorophenyl)oxoacetic acid, and formaldehyde as a byproduct, are different from those obtained by biological metabolism. The reaction is first-order in MnO4- and less than first-order in both the clopidogrel hydrogen sulfate and H+. ion concentrations. The active species of permanganate was found to be HMnO4. The oxidation reaction in acid medium was found to proceed through a permanganate-clopidogrel complex that decomposes slowly in a rate-determining step followed by other fast steps to give the products. The main products were identified by spot test and IR and GC-MS spectral studies. The reaction constants involved in different steps of the mechanism were calculated at different temperatures. The activation parameters with respect to the slow step of the mechanism were computed, and thermodynamic quantities were also determined.