Androgen deprivation therapy (ADT) is a cornerstone of prostate cancer treatment.  However, after initial success with ADT, a subset of patients can develop a more aggressive, castration-resistant prostate cancer (CRPC).  The clinical efficacy of the CYP17A1 inhibitor, abiraterone acetate, in the treatment of CRPC confirms that the disease remains hormonally driven.  Quantification of the androgen metabolome in serum and tumor biopsies can inform one as to the metabolic pathway that has been activated in individuals with CRPC.  To this end, a stable isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry (SID-LC-ESI-MS/MS) method has been developed to detect ketosteroids as Girard T oximes and hydroxysteroids as picolinic esters.  Accuracy and precision values have been obtained for ketosteroid quantification and glucuronate and sulfate conjugates quantitated using enzymatic hydrolysis.  We have applied our method to quantify serum androgen levels from patients enrolled in the Total Androgen Pathway Suppression (TAPS) Trial.

Development of stable isotope dilution liquid chromatography tandem mass spectrometry (LS-MS/MS) methods for the determination of the androgen metabolome in serum following androgen deprivation therapy

244th National Meeting (2012)

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