Improved method for the quantification of aminoglutethimide in urine samples.
Due to an unknown mechanism aminoglutethimide (AG) in urine samples is partly present in a form in which it is not detected. Though most evident if samples had been stored at -20 degrees C (about 60% trapped), it also occurred in fresh urine samples (about 20% trapped). Heating the urine sample for 15 min at 100 degrees C liberated all AG. This phenomenon has led to the underestimation of the excretion of unchanged AG in previous publications. This study shows that AG was excreted unchanged for 47.5 +/- 7.3% (mean +/- SD) in patients received 2 X 125 mg or 2 X 250 mg AG. Direct measurement of hydroxylaminoglutethimide (HxAG) was found difficult, due to its instability with respect to oxidation. We found azoxyG to be a stable oxidation product derived from HxAG. The concentration of azoxyG formed was proportional to the amount of HxAG converted. HxAG seemed subjected to the same phenomenon as AG. A conversion of HxAG into an unknown compound which seemed to occur very easily and which was even accelerated by heating, made it impossible to accurately measure the concentration of HxAG.
van Tellingen
O
O
Department of Clinical Chemistry, Antoni van Leeuwenhoekhuis, Amsterdam, The Netherlands.
Bonfrer
J M
JM
Nooyen
W J
WJ
Bruning
P F
PF
D000616:Aminoglutethimide / Q000008:administration & dosage / Q000652:urine*; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008722:Methods; D010084:Oxidation-Reduction; D013048:Specimen Handling
D000616:Aminoglutethimide