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

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.