Quantitative determination of proxalutamide in rat plasma and tissues using liquid chromatography/tandem mass spectrometry

Rapid Commun Mass Spectrom. 2021 Feb 15;35(3):e9003. doi: 10.1002/rcm.9003.


Rationale: Proxalutamide is a novel drug for the treatment of prostate cancer. However, to date, there are almost no reports on the pharmacokinetics of proxalutamide in vivo. This study developed a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method to determine the concentrations of proxalutamide in biological samples for pharmacokinetic studies.

Methods: Chromatographic separation was achieved on a Kromasil 100-5C8 column followed by gradient elution using a Shimadzu HPLC system. MS was performed in positive ion electrospray ionization mode using a SCIEX API 4000 triple quadrupole system. A simple and rapid one-step protein precipitation method was used for sample processing, and a low sample volume of 10 μL was used for processing and analysis.

Results: The method was validated to show good selectivity, sensitivity, precision, and accuracy. Good linearity (r2 > 0.99) was observed for rat plasma (range: 2-5000 ng/mL) and rat tissue homogenates (range: 2-2000 ng/mL). The extraction recovery was above 98%, and no significant matrix effect was observed. This method was successfully applied to investigate the pharmacokinetics and tissue distribution of proxalutamide in rats.

Conclusions: A rapid and sensitive LC/MS/MS method was developed and validated to determine the quantity of proxalutamide in rat plasma and tissue homogenates and to further study the pharmacokinetic parameters of proxalutamide in a rat model. The results showed that proxalutamide had good oral bioavailability and wide tissue distribution in vivo.

Publication types

  • Evaluation Study

MeSH terms

  • Animal Structures / chemistry
  • Animal Structures / metabolism
  • Animals
  • Biological Availability
  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Male
  • Oxazoles / administration & dosage
  • Oxazoles / blood
  • Oxazoles / pharmacokinetics*
  • Plasma / chemistry*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*
  • Thiohydantoins / administration & dosage
  • Thiohydantoins / blood
  • Thiohydantoins / pharmacokinetics*
  • Tissue Distribution


  • Oxazoles
  • Thiohydantoins
  • proxalutamide