LC-MS/MS assay for the quantification of testosterone, dihydrotestosterone, androstenedione, cortisol and prednisone in plasma from castrated prostate cancer patients treated with abiraterone acetate or enzalutamide

Abstract

Prostate cancer is the most common malignancy among men in the Western world. Treatment of this patient population, e.g. by (chemical) castration, is primarily focused on depletion of tumor-stimulating androgens, with testosterone being the major androgenic hormone. After initial therapy, prostate cancer may progress to metastatic castration-resistant prostate cancer. Anti-hormonal drugs abiraterone acetate and enzalutamide are commonly used to treat patients with this disease as both drugs reduce tumor growth and increase time to tumor progression. To evaluate the pharmacodynamic effects of anti-hormonal drugs in this patient population, we developed an LC-MS/MS method for the quantification of testosterone, dihydrotestosterone, androstenedione, cortisol and prednisone in human plasma. The validated assay ranges from 10-10,000 pg/mL for testosterone and androstenedione, 100-10,000 pg/mL for dihydrotestosterone, 50-5000 pg/mL for cortisol and 500-50,000 pg/mL for prednisone. Intra-assay and inter-assay variabilities were within ±15% of the nominal concentrations for quality control (QC) samples at low, medium and high concentrations and within ±20% at the lower limit of quantification (LLOQ), respectively. The applicability of the method was demonstrated in plasma from patients with metastatic castrated-resistant prostate cancer using either abiraterone acetate or enzalutamide.