Effects of liver disease on fecal excretion of methadone and its unconjugated metabolites in maintenance patients. Quantitation by direct probe chemical ionization mass spectrometry.

This study was performed to determine the amounts of methadone and unconjugated metabolites excreted in feces of otherwise healthy methadone maintained patients and to determine whether the metabolism and elimination of methadone, as assessed by analysis of feces, is altered in patients with liver disease. The method for analysis of fecal homogenates was modified from the methods previously developed by our laboratories for the quantitative measurements of methadone and its metabolites in urine, using chemical ionization mass spectrometry with direct probe insertion of specimens to improve sensitivity of analysis. Analysis of fecal homogenates from unmedicated volunteer patients showed that interferences at the mass range of interest (m/z 264 to 326) were usually very small, even smaller than those found in analyses of unmedicated urine specimens, and therefore would not introduce significant error into analysis. Nineteen patients stabilized in chronic methadone treatment for over two years were studied, including five otherwise healthy males and 14 patients with chronic liver disease (nine males and five females). Fecal collections were made over 24 h periods. Three consecutive fecal samples were collected over the required number of sequential 24 h intervals. Each of these fecal conditions was analysed separately. Each analysis was made in triplicate, following extraction procedures. The concentrations of methadone and unconjugated metabolites varied due to biological, pharmacological, and analytical factors and ranged from 3.8 ng ml-1 to 42 micrograms ml-1 of fecal homogenate. The relative concentrations of each, in descending order, were pyrrolidine, pyrrolidone (plus hydroxymethadone), methadone, pyrroline, and methadol.(ABSTRACT TRUNCATED AT 250 WORDS)