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, co-elution with metabolites, and carry-over issues. Limited stability (2h) 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 24h and in whole blood for 8h. 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 1–500 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.

Estimation of abiraterone in human plasma by liquid chromatography tandem mass spectrometry

“…It utilizes liquid-liquid extraction technique for this relatively non-polar molecule which offers consistent and reproducible recoveries with insignificant interference and matrix effect. Moreover, this method does not have any carry -over problem as reported earlier 11 . Stability issue of abiraterone in plasma has been resolved by using potassium fluoride 14,15 .…”

“…No carry -over was observed during the experiment. Benoist et al 11 encountered with the carry -over in their recently published method which had been eliminated by using one more solvent as the mobile phase in their gradient method. However, our method is relatively simple where only isocratic elution was done without any carry -over problem.…”

“…Several chromatographic methods have been reported for determination of abiraterone in plasma [6][7][8][9][10][11] . However, these methods had their own limitations in respect to the sample preparation, gradient elution, run time, etc.…”

“…They used Phenacetin as an internal standard and protein precipitation method for sample extraction. In a recently published article, the abiraterone was estimated by LCMS/MS using a gradient method 11 . In this method, sample extraction was done by protein precipitation and deuterated abiraterone was used as an internal standard.…”

A clinically relevant decrease in abiraterone exposure associated with carbamazepine use in a patient with castration‐resistant metastatic prostate cancer

“…This time period was considered to be appropriate to reach maximal inducing effects on metabolizing enzymes and steady‐state pharmacokinetics of abiraterone. Abiraterone was measured with our validated LC‐MS/MS method that is described in further detail in a previously published article . The assay ranged from 1 to 500 ng ml −1 , and the limit of detection was 0.01 ng ml −1 .…”