Characterisation of metabolites of 3-ethyl-3-(4-pyridyl)-piperidine-2,6-dione, a potential breast cancer drug.
The identification of metabolites from the pyridylglutarimide 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione (PG, Rogletimide) was achieved using liquid chromatography-mass spectrometry with a thermospray interface (LC-TSP-MS). The urinary metabolites include PG N-oxide, the products of 4- and 5-hydroxylation in the piperidine residue (4- and 5-hydroxy-PG) and a gamma-butyrolactone derived via terminal hydroxylation in the ethyl residue. In addition to the above metabolites, several products of glutarimide ring-opening could be detected in the plasma extracts after multiple-dose treatment. Thus LC-TSP-MS is potentially a simple and rapid technique in studies of drug metabolism for the important glutarimide class of drug.
Poon
G K
GK
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, UK.
McCague
R
R
Griggs
L J
LJ
Jarman
M
M
Lewis
I A
IA
D000616:Aminoglutethimide / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use / Q000652:urine; D001943:Breast Neoplasms / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D012015:Reference Standards
D000970:Antineoplastic Agents; D000616:Aminoglutethimide; C049837:rogletimide