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Radical Mechanisms in the Radiosterilization of Metoprolol Tartrate Solutions
Authors:Catherine Slegers  Gérard Baldacchino  Dominique Le Parc  Bernard Hickel  Bernard Tilquin
Affiliation:Unité d'Analyse Chimique et Physico-chimique des Médicaments, Université Catholique de Louvain, Brussels, Belgium. catherine.slegers@cham.ucl.ac.be
Abstract:PURPOSE: Study of the radical mechanisms in the radiosterilization of metoprolol tartrate aqueous solutions in order to determine the parameters governing its radiostability. METHODS: Pulse radiolysis with pseudo-first-order kinetics to measure Ihe reaction rate constants of hydrated electrons and hydroxyl radicals with metoprolol tartrate. Chemsimul was used to solve the decay kinetics of transients and to simulate the radiolysis of metoprolol tartrate solutions. RESULTS: Hydrated electrons react with metoprolol and the tartrate ion with rate constants of 6.8 x 10(7) M(-1) s(-1) and 1.7 x 10(7) M(-1) s(-1), respectively. Hydroxyl radicals react with metoprolol and the tartrate ion with rate constants of 5.2 x 10(9) M(-1) s(-1) and 5.5 x 10(8) M(-1) s(-1), respectively. The hydroxyl-metoprolol transients are found to scavenge the superoxide anion (5.5 x 10(10) M(-1) s(-1)), react with oxygen (1.0 x 10(8) M(-1) s(-1)), and follow a biradical decay (2.0 x 10(8) M(-1) s(-1). A simplified radical mechanism is used to simulate the loss of potency of metoprolol tartrate aqueous solutions during radiosterilization. CONCLUSIONS: To decrease the loss of potency of metoprolol tartrate. the sterilization dose must be lowered and very high dose rates used.
Keywords:radiosterilization  drug aqueous solution  rate constant measurements  computer simulation  metoprolol tartrate
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