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Effects of liver disease on fecal excretion of methadone and its unconjugated metabolites in maintenance patients. Quantitation by direct probe chemical lonization mass spectrometry
Author(s) -
Kreek Mary Jeanne,
Bencsath F. A.,
Fanizza Angela,
Field Frank H.
Publication year - 1983
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200101003
Subject(s) - feces , excretion , mass spectrometry , chemistry , methadone maintenance , chromatography , methadone , pharmacology , medicine , biology , microbiology and biotechnology
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 collections 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 μg ml −1 of fecal homogenate. The relative concentrations of each, in descending order, were pyrrolidine, pyrrolidone (plus hydroxymethadone), methadone, pyrroline, and methadol. The 24 h fecal excretion of methadone and its unconjugated metabolites was 8.4% (±0.9 SEM) of the administered methadone dose in otherwise healthy normal patients, 9.4% (±1.0 SEM) in male patients with chronic liver disease, and 12.3% (±1.9 SEM) in female patients with chronic liver disease; none of these values was significantly different from the others. The total amounts of methadone and of each unconjugated metabolite excreted in feces were not significantly different in patients with liver disease as compared with otherwise healthy patients.