Analysis of [14C]-saterinone and its metabolites in dog plasma, urine and bile by high-performance liquid chromatography with radioactivity and fluorescence detection and by mass spectrometry.
An HPLC method was developed for the direct on-line radioactivity determination of [14C]-saterinone and its metabolites in biological canine fluids after intravenous and intraduodenal administration. After direct injection of 200 microliters of sample, the metabolites were separated on a semi-preparative reverse-phase column. The metabolites were identified by HPLC reference standards, enzymatic hydrolysis and mass spectrometry. Besides a small amount of unchanged saterinone, six metabolites could be detected, both in bile and urine. The main fraction (about 80-90% of the sum of detected metabolites) contained the phase II metabolites of saterinone, the sulphate and glucuronide. Ring hydroxylated saterinone and three metabolites that were not identified made up about 1-4% each. In plasma, only the major compounds could be detected because of the lower absolute concentrations. The metabolic pathway of saterinone in dogs was elucidated and compared with other species. Results from previous studies concerning a first-pass metabolism could be confirmed.
Rudolph
M
M
Pharmaceutical Development, Beiersdorf AG, Hamburg, Germany.
Schmiedel
G
G
D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry*; D002316:Cardiotonic Agents / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006868:Hydrolysis; D008297:Male; D013058:Mass Spectrometry; D010879:Piperazines / Q000032:analysis* / Q000097:blood / Q000652:urine; D011728:Pyridones / Q000032:analysis* / Q000097:blood / Q000652:urine; D013050:Spectrometry, Fluorescence
D001647:Bile Acids and Salts; D002316:Cardiotonic Agents; D010879:Piperazines; D011728:Pyridones; C058572:saterinone