Development and validation of a novel LC-MS/MS method for simultaneous determination of abiraterone and its seven steroidal metabolites in human serum: Innovation in separation of diastereoisomers without use of a chiral column.
J Steroid Biochem Mol Biol
; 172: 231-239, 2017 09.
Article
en En
| MEDLINE
| ID: mdl-27063554
ABSTRACT
Abiraterone acetate (AA), the prodrug of abiraterone, is FDA-approved for the treatment of castration-resistant prostate cancer. Abiraterone is metabolized in patients to a more potent analogue, D4A. However, we have recently reported that this analogue is further metabolized to additional metabolites in patients treated with AA. Here, we present a liquid chromatography-tandem mass spectrometry method developed to resolve and detect abiraterone and its seven metabolites in human serum using an AB Sciex Qtrap 5500 mass analyzer coupled with a Shimadzu Nexera UPLC station. Analytes and the internal standard (abiraterone-d4) were extracted from human serum using the liquid-liquid extraction procedure. The analytes were separated using a Zorbax Eclipse Plus C18 150×2.1mm, 3.5µm column at 40°C and an isocratic mobile phase 35% A (0.1% formic acid in water), 65% B (0.1% formic acid in methanolacetonitrile; 6040). Electrospray ionization in positive mode was applied with multiple reaction monitoring in a total run time of 13min. Abiraterone detection was linear in the range 2-400ng/mL and all metabolites from 0.1-20ng/mL. The method was validated following US FDA guidelines for bioanalytical method validation, and all the metabolite results were within the acceptance limits. Despite the similarity in structure and mass transition between the metabolites, the validated method separated all the metabolites, including diastereomers, to allow accurate identification and quantitation of each compound.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Profármacos
/
Cromatografía Liquida
/
Antineoplásicos Hormonales
/
Espectrometría de Masas en Tándem
/
Neoplasias de la Próstata Resistentes a la Castración
/
Acetato de Abiraterona
Tipo de estudio:
Guideline
/
Prognostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos