Determination of 4-hydroxyandrost-4-ene-3,17-dione metabolism in breast cancer patients using high-performance liquid chromatography-mass spectrometry.
A sensitive procedure for studying the metabolism of the steroidal aromatase inhibitor 4-hydroxy-androst-4-ene-3,17-dione (4OHA) was developed based on enzyme hydrolysis, liquid-liquid extraction and reversed-phase liquid chromatography coupled with a mass spectrometer (LC-MS) using a thermospray interface. Seven metabolites were identified from the hydrolysed urine samples together with the parent drug. The major routes of metabolism were via dehydrogenation, reduction of the ketone functional groups, reduction at the C-4-C-5 double bond and hydroxylation at the C-5 position. Confirmation of the identity of 4OHA and its metabolites isolated from female patients' urine samples was accomplished by comparison of the retention times of their corresponding synthetic standards on LC-MS. We have demonstrated that this technique is particularly suitable for studying the metabolism of steroidal drugs.
Poon
G K
GK
Cancer Research Campaign Laboratory, Institute of Cancer Research, Sutton, Surrey, U.K.
Jarman
M
M
Rowlands
M G
MG
Dowsett
M
M
Firth
J
J
D000284:Administration, Oral; D000735:Androstenedione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000652:urine; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*
D047072:Aromatase Inhibitors; D000735:Androstenedione; C014594:formestane