Structural determination of the conjugated metabolites of ritodrine

Ritodrine is a beta-2 adrenergic agonist which is used clinically for the management of preterm labor. Since ritodrine is resistant to the action of monoamine oxidase and catecholamine-O-methyltransferase, conjugation is a major route of metabolism. Glucuronide and sulfate conjugates of ritodrine are found in maternal urine. However, the structure of these metabolites has not been determined. The purpose of this study was to determine the structure of these conjugates. Urine from patients on ritodrine therapy was purified by QAE Sephadex ion exchange chromatography. The partially purified conjugates were derivatized and analyzed by GC/MS. The data did not indicate an exclusive site of conjugation. Analysis of both the glucuronide and sulfate conjugates indicates that either of the two phenolic hydroxyl groups may be involved in the formation of conjugated metabolites. However, conjugation of the [2-(p-hydroxyphenyl)-2-hydroxy-1-methylethyl]amine phenolic hydroxyl is more prevalent for both conjugates. This phenolic hydroxyl group is unique since it is located on the portion of the ritodrine molecule which more closely resembles the structure of endogenous catecholamines.