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Analytical challenges in quantifying abiraterone with LC–MS/MS in human plasma
Author(s) -
Benoist Guillemette E.,
Meulen Eric,
Lubberman Floor J.E.,
Gerritsen Winald R.,
Smilde Tineke J.,
Schalken Jack A.,
Beumer Jan H.,
Burger David M.,
Erp Nielka P.
Publication year - 2017
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3986
Subject(s) - abiraterone , chromatography , protein precipitation , bioanalysis , chemistry , analyte , mass spectrometry , tandem mass spectrometry , prostate cancer , cancer , medicine , androgen receptor
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.