1: Pharm Res.  2003 Dec;20(12):1977-83.  

Radical mechanisms in the radiosterilization of metoprolol tartrate solutions.

Slegers C, Baldacchino G, Le Parc D, Hickel B, Tilquin B.

Unite d'Analyse Chimique et Physico-chimique des Medicaments, Universite
Catholique de Louvain, Brussels, Belgium. catherine.slegers@cham.ucl.ac.be

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.

PMID: 14725362 [PubMed - in process]