Selinexor is a nuclear exportin-1 (XPO1) inhibitor that has been approved for the treatment of multiple myeloma patients. However, sustained use of selinexor may result in some undesirable consequences. Furthermore, selinexor has moderate inter-patient variability. Herein, we developed an ultrahigh-performance liquid chromatography tandem mass spectrometry method for measuring selinexor levels in human plasma ranging from 1 to 1000 ng mL-1. Furthermore, the developed approach was validated in accordance with FDA criteria. The established approach demonstrated inter-day and intra-day precision, expressed as the relative standard deviation, of less than 8%, with accuracies of less than 6%, expressed as relative error. The results showed that the protein depletion was quite complete for selinexor extraction, with recoveries ranging from 85.89 to 108.38%. The validated method facilitates the quantitation of selinexor in multiple myeloma patients. The selinexor plasma concentration exhibits obvious inter-patient' variability after administration. Thus, it is necessary to make a personalized prescription through therapeutic drug monitoring. Furthermore, the change in platelet counts before and after selinexor treatment was shown to be related to the plasma concentration at 3 h after administration, which provides the basis for therapeutic drug monitoring sampling time points and a method for predicting the occurrence of thrombocytopenia. In conclusion, the developed method can be used for the quantification of the plasma concentration of selinexor, and it is of great significance to conduct therapeutic drug monitoring for patients taking selinexor in order to enhance therapeutic effects and prevent the occurrence of adverse reactions.