Simultaneous quantitation of abiraterone, enzalutamide, N-desmethyl enzalutamide, and bicalutamide in human plasma by LC-MS/MS
Publication year
2017Source
Journal of Pharmaceutical and Biomedical Analysis, 138, (2017), pp. 197-205ISSN
Publication type
Article / Letter to editor
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Organization
Clinical Pharmacy
Journal title
Journal of Pharmaceutical and Biomedical Analysis
Volume
vol. 138
Page start
p. 197
Page end
p. 205
Subject
Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health SciencesAbstract
Inhibiting the androgen receptor (AR) pathway is an important clinical strategy in metastatic prostate cancer. Novel agents including abiraterone acetate and enzalutamide have been shown to prolong life in men with metastatic, castration-resistant prostate cancer (mCRPC). To evaluate the pharmacokinetics of AR-targeted agents, we developed and validated an LC-MS/MS assay for the quantitation of enzalutamide, N-desmethyl enzalutamide, abiraterone and bicalutamide in 0.05mL human plasma. After protein precipitation, chromatographic separation was achieved with a Phenomenex Synergi Polar-RP column and a linear gradient of 0.1% formic acid in methanol and water. Detection with an ABI 4000Q mass spectrometer utilized electrospray ionization in positive multiple reaction monitoring mode. The assay was linear over the ranges of 1-1000ng/mL for abiraterone and bicalutamide and 100-30,000ng/mL for N-desmethyl enzalutamide and enzalutamide and proved to be accurate (92.8-107.7%) and precise (largest was 15.3% CV at LLOQ for bicalutamide), and fulfilled FDA criteria for bioanalytical method validation. We demonstrated the suitability of this assay in plasma from patients who were administered enzalutamide 160mg, abiraterone 1000mg and bicalutamide 50mg once a day as monotherapy or in combination. The LC-MS/MS assay that has been developed will be an essential tool that further defines the pharmacology of the combinations of androgen synthesis or AR-receptor targeted agents.
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- Academic publications [238430]
- Faculty of Medical Sciences [90359]
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