Mechanism and Kinetics Studies of Oxidation of the Pharmaceutical Drug Amlodipine Besylate by N-bromosuccinimide in Aqueous Acidic Medium

Abstract

The oxidation of the pharmaceutical drug Amlodipine besylate [AML] by N-Bromosuccinimide [NBS] was investigated aqueous acidic medium under pseudo-first-order condition. The experimental results indicated that the reaction exhibits first-order concerning N-bromosuccinimide, fractional order concerning [AML] and sulphuric acid [H₂SO₄]. There was no substantial effect on the rate of the reaction with KNO₃. The reaction stoichiometry shows one mole of amlodipine besylate consumes one mole of n-bromosuccinimide. The effect of temperature on the reaction rate was studied, and the activation parameters (E_a, △G, △H and △S) are calculated and tabulated. LC-MS technique was used to identify the oxidation product of amlodipine besylate. Based on experimental results, a mechanism is proposed, and constants K₁, K₂ and k₃ involved in the mechanism were evaluated. The observed rate constant values and the experimental value calculated by substituting the value of k₃= 4.0 × 10⁻³ s ⁻¹, K₂ = 1272 moldm^-3s⁻¹ and K₁= 1.96 x 10⁻⁶ in the rate equation is in good accordance with each other.