Voltammetric and capillary electrophoretic study of scavenger kinetics of methylglyoxal by antidiabetic biguanide drugs

• Ion transfer voltammetry is introduced for kinetic measurements of methylglyoxal scavenging by antidiabetic biguanide drugs.
• Simultaneous assay of a biguanide and methylglyoxal by capillary electrophoresis yields their stoichiometric ratio.
• Rate constants are determined and reaction mechanism is proposed involving acid-base reaction of biguanide.

A novel electroanalytical approach is used to get insight into scavenger kinetics and mechanism of methylglyoxal (MG) by biguanides metformin, phenformin and 1-phenylbiguanide under the physiological conditions (pH 7.41 and 37 °C). The approach is based on monitoring the time profiles of concentrations of the protonated biguanides by ion transfer voltammetry (ITV) at the polarizable room-temperature ionic liquid membrane. Effects of the reactant's concentrations and pH lead us to propose a mechanism including an acid-base reaction of biguanide, which separates the parallel reactions of the protonated and deprotonated biguanide with methylglyoxal. Reaction rate increases considerably in the sequence metformin < phenformin < 1-phenylbiguanide. Kinetic data confirm the previous finding that scavenging of methylglyoxal by metformin is a relatively slow process. Optimization of the background electrolyte enables to use capillary electrophoresis (CE) to detect simultaneously the protonated biguanide and the MG anion in the reaction mixture. CE analysis then yields the mole-to-mole ratios of the reacted biguanides to MG in the range 0.6–0.7 pointing to the simultaneous formation of a 1:1 and a 1:2 reaction products. Usefulness of ion voltammetry or amperometry for further kinetic studies of biguanides, as well as for their assays, can be envisaged.

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