Establishment and Verification of UPLC-MS/MS Technique for Pharmacokinetic Drug–Drug Interactions of Selinexor with Posaconazole in Rats

Abstract

Background

A method for the determination of selinexor by UPLC-MS/MS was established to study the effect of posaconazole on the pharmacokinetics of selinexor in rats.

Methods

The experiment rats were divided into group A (0.5% CMC-Na) and group B (posaconazole, 20 mg/kg), 6 rats in each group. 30 minutes after administration of 0.5% CMC-Na or posaconazole, all the rats were given selinexor (8 mg/kg), and plasma samples were collected. The plasma samples underwent acetonitrile protein precipitation, and were separated by UPLC on an Acquity UPLC BEH C18 column with gradient elution. Acetonitrile and 0.1% formic acid were used as the mobile phases. The analyte detection was used a Xevo TQ-S triple quadrupole tandem mass spectrometer and multiple reaction monitoring (MRM) for analyte monitoring. We use acetonitrile for protein precipitation.

Results

Selinexor had good linearity (1.0–1000 ng/mL, r ² ₌0.996 2), and the accuracy and precision, recovery rate and matrix effects(ME) were also met the FDA approval guidelines. Compared with group A, the C _max, AUC _(0−t) and AUC _(0−∞) of selinexor in group B increased by 60.33%, 48.28% and 48.27%, and T _max increased by 53.92%, CLz/F reduced by 32.08%.

Conclusion

This bioanalysis method had been applied to the study of drug interactions in rats. It was found that posaconazole significantly increased the concentration of selinexor in rats. Therefore, when selinexor and posaconazole are combined, we should pay attention to the possible drug–drug interactions to reduce adverse reactions.