Analytical challenges in quantifying abiraterone with LC-MS/MS in human plasma

Area of Science:

• Analytical Chemistry
• Pharmacokinetics
• Mass Spectrometry

Background:

• Abiraterone acetate is a key treatment for metastatic castration-resistant prostate cancer.
• Accurate quantification of abiraterone in plasma is essential for therapeutic drug monitoring.
• Previous methods faced challenges including sample stability and analytical interferences.

Purpose of the Study:

• To develop and validate a robust bioanalytical method for quantifying abiraterone in human plasma.
• To address and overcome specific analytical challenges encountered during assay development.

Main Methods:

• Abiraterone was extracted from plasma via protein precipitation.
• Chromatographic separation was achieved using a C18 column with gradient elution.
• Quantification was performed using tandem quadrupole mass spectrometry (MS/MS) in positive ion mode with a deuterated internal standard.

Main Results:

• The assay demonstrated limited abiraterone stability at ambient temperature but was stable for 24 hours at 2-8°C in plasma.
• Adsorption issues were mitigated using polypropylene materials, and carry-over was reduced by optimizing the mobile phase gradient.
• The validated assay range is 1-500 ng/mL, with excellent precision and accuracy (within 13.4% and 95-102%, respectively).

Conclusions:

• A reliable and validated bioanalytical method for abiraterone quantification in human plasma was established.
• This method successfully addresses critical analytical challenges, ensuring accurate measurement.
• The validated assay is suitable for clinical studies and routine patient monitoring in prostate cancer management.