Improved method for the quantification of aminoglutethimide in urine samples

Area of Science:

• Pharmacology
• Analytical Chemistry
• Clinical Chemistry

Background:

• Aminoglutethimide (AG) is used clinically, and its excretion profile is important for therapeutic monitoring.
• Previous studies may have underestimated unchanged AG excretion due to sample handling.
• The stability and detection of AG and its metabolites in biological samples require further investigation.

Purpose of the Study:

• To investigate the mechanism causing undetectable aminoglutethimide (AG) in urine samples.
• To determine the extent of unchanged AG excretion in patients.
• To explore the stability and detection of hydroxylaminoglutethimide (HxAG) and its metabolites.

Main Methods:

• Analysis of AG in fresh and stored urine samples.
• Assessment of AG liberation upon heating urine samples.
• Investigation of hydroxylaminoglutethimide (HxAG) stability and its oxidation product, azoxyG.

Main Results:

• A significant portion of AG is present in an undetectable form in urine, both fresh (~20%) and stored (~60%).
• Heating urine samples at 100°C for 15 minutes completely liberates the trapped AG.
• Unchanged AG excretion was measured at 47.5 ± 7.3% in patients receiving AG.
• Hydroxylaminoglutethimide (HxAG) is unstable and difficult to measure directly due to rapid conversion to an unknown compound, even with heating.

Conclusions:

• An unknown mechanism causes AG to be partially undetectable in urine, leading to underestimation of excretion in prior research.
• Accurate measurement of AG excretion requires methods that account for this sample instability, such as heating.
• The instability of HxAG complicates the assessment of its role and metabolism in vivo.