title: Analytical challenges in quantifying abiraterone with LC-MS/MS in human plasma.
abstract: A method was developed and validated to quantify abiraterone in human plasma. During assay development, several analytical challenges were encountered: limited stability in patient samples, adsorption to glass, coelution with metabolites and carry-over issues. Limited stability (2 h) was found for abiraterone in fresh plasma as well as whole blood at ambient temperature. When kept at 2-8°C, abiraterone in plasma was stable for 24 h and in whole blood for 8 h. Adsorption of abiraterone to glass materials was addressed by using polypropylene throughout the method. Carry-over was reduced to acceptable limits by incorporating a third mobile phase into the gradient. The chromatographic separation of abiraterone with its multiple metabolites was addressed by using a longer analytical column and adjusting the gradient. Abiraterone was extracted by protein precipitation, separated on a C18 column with gradient elution and analyzed with tandem quadrupole mass spectrometry in positive ion mode. A stable deuterated isotope was used as the internal standard. The assay ranges from 1 to 500 ng/mL. Within- and-between-day precisions and accuracies were below 13.4% and within 95-102%. This bioanalytical method was successfully validated and applied to determine plasma concentrations of abiraterone in clinical studies and in regular patient care for patients with metastatic castration-resistant prostate cancer.
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Guillemette E
authors.identifier: http://orcid.org/0000-0002-3432-3575
authors.initials: GE
authors.lastname: Benoist
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: van der Meulen
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Floor J E
authors.initials: FJE
authors.lastname: Lubberman
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Winald R
authors.initials: WR
authors.lastname: Gerritsen
authors.affiliation: Department of Medical Oncology, Jeroen Bosch Hospital, Den Bosch, Netherlands.
authors.forename: Tineke J
authors.initials: TJ
authors.lastname: Smilde
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Schalken
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Beumer
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Nielka P
authors.initials: NP
authors.lastname: van Erp
mesh_terms: D000736:Androstenes / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature
chemical_list: D000736:Androstenes; C089740:abiraterone
keywords: LC-MS/MS; abiraterone; abiraterone acetate; stability; validation