Biliary secretion of methadone and methadone metabolites in man

A method for the simultaneous quantitative analysis of human bile for methadone, and two of its metabolites: pyrrolidine, the major metabolite formed by N-demethylation, and pyrroline, formed by a second N-demethylation, using gas liquid chromatography and both radiolabeled methadone and pyrrolidine as standards for determinations of recovery has been developed. This method has been applied to the quantitative analysis of methadone and its metabolites in bile collected over three days from T-tube drainage in a methadone-maintained patient who had undergone cholecystectomy and common bile duct exploration but who had no liver disease. The concentrations and total amounts of the pyrrolidine metabolite far exceeded those of methadone and of the pyrroline metabolite. The amounts of unchanged methadone found in bile (as in previous studies of feces) were found to be very low. Therefore, at least in this patient, a significant enterohepatic circulation of unchanged methadone is unlikely.