期刊
THERAPEUTIC DRUG MONITORING
卷 39, 期 3, 页码 243-251出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FTD.0000000000000387
关键词
abiraterone; enzalutamide; metabolites; N-desmethyl enzalutamide; LC-MS/MS; therapeutic drug monitoring
Background: Abiraterone acetate and enzalutamide are 2 novel drugs for the treatment of metastatic castration-resistant prostate cancer. The metabolism of these drugs is extensive. Major metabolites are N-desmethyl enzalutamide, enzalutamide carboxylic acid, abiraterone N-oxide sulfate, and abiraterone sulfate; of which N-desmethyl enzalutamide is reported to possess antiandrogen capacities. A liquid chromatography-tandem mass spectrometry method for simultaneous quantification of abiraterone, enzalutamide, and the main metabolites has been developed and validated to support therapeutic drug monitoring. Methods: Human plasma samples of patients treated with abiraterone or enzalutamide were harvested at the clinic and stored at -20 degrees C. Proteins were precipitated by acetonitrile, and the final extract was injected on a Kinetex C18 column and separated with gradient elution. Analytes were detected by liquid chromatographymass spectrometry (Triple Quad 6500). Results: The method was validated over various linear ranges: 1-100 ng/mL for abiraterone, 5-500 ng/mL for enzalutamide and enzalutamide carboxylic acid, 10-1000 ng/mL for N-desmethyl enzalutamide, 30-3000 ng/mL for abiraterone N-oxide sulfate, and 100-10,000 ng/mL for abiraterone sulfate. Intra-assay and interassay variabilities were within +/-15% of the nominal concentrations for quality control samples at medium and high concentrations and within +/-20% at the lower limit of quantification, respectively. Conclusions: The described method for simultaneous determination of abiraterone and enzalutamide was validated successfully and provides a useful tool for therapeutic drug monitoring in patients treated with these agents.
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