Quinidine, an antiarrhythmic agent, is known to cause a number of immunologically mediated side effects. One of these, a kind of granulomatous hepatitis, occurs in about 5 percent of the patient population. It is believed that the problem is not caused by the drug itself but rather by a reactive intermediate covalently binding to a protein. Previous investigations have been able to account for only about 50 percent of a quinidine dose in terms of the parent drug and known metabolites. One of these metabolites is the 10,11-diol. The formation of diols is known to proceed via epoxides. Epoxides are known to covalently bind to tissue macro- molecules. This study was undertaken to determine if quinidine, after metabolic activation, could covalently bind to proteins and thus possibly cause these side effects.
KeywordsHPLC Hepatitis Filtration Cysteine MeOH
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