David L. Hachey

Stereoselective disposition of methadone in man

Abstract Stable isotope labeled methadone (pentadeuteromethadone) has been used in conjunction with gas chromatography-chemical ionization mass spectrometry to study plasma disappearance rates and urinary excretion of pharmacologically active R-(−)-methadone (l-methadone) and inactive S-(+)-methadone (d-methadone) in three adult methadone maintenance patients. In all three cases, the analgesically active enantiomeric form of the drug had a significantly longer elimination half-life ( t 1 2 β ) when studied in a steady state than did the inactive form ( t 1 2 β for active R-(−)-methadone, 51.7 to 61.8 hours; t 1 2 β for inactive S-(+)-methadone, 31.8 to 37.0 hours). The ratio of drug elimination half-lives } R-(−)-/S-(+)- ranged between 1.40 and 1.94. In the two cases so studied, slower plasma disappearance of active R-(−)-enatiomer than the inactive S-(+)-enantiomer was also observed ( t 1 2β R-(−)-, 42.8 and 52.5 hours; t 1 2β S-(+)-, 38.3 and 41.3 hours).

Separation of bile acids as their phenacyl esters by high-pressure liquid chromatography

Abstract Bile acids have been separated by high-pressure liquid chromatography. The free acids were derivatized to their phenacyl esters by treatment with triethylamine and α-bromoacetophenone. The stationary phase was a C 18 , Partisil ODS column. A dual-solvent, stepwise gradient system was used for the mobile phase. The method is applied to a human bile sample and shows excellent resolution of the dihydroxy bile acid phenacyl esters. Detection limits for pure derivatized bile acids are 10–20 pmol (5–10 ng), except for the cholic acid derivative, which has a detection limit of 265 pmol.

Stable isotopes: essential tools in biological and medical research

The renaissance of interest in stable isotopes of hydrogen, carbon, nitrogen, oxygen and sulphur within the last ten years is based upon the development of new instrumentation, on the greater availability of enriched isotopes and on an espousal of non-radioactive techniques for human studies on ethical grounds. In order to put the present use of stable isotopes into perspective, we should examine both its antecedents and its expectations, so that we can judge the benefits to be expected.