Transporters belonging in the ATP-binding cassette (ABC) family are crucially involved in the determination
of the pharmacokinetic behavior of xenobiotics and in the development of drug resistance. The targeting of these transporters
has been accepted as a rational option via which to modify the absorption or distribution of pharmaceutical agents
and to combat ABC-related inefficiency. Inhibitors of the breast cancer resistance protein (BCRP/ABCG2) multidrug
transporter are of interest as chemosensitizers for clinical drug resistance, for improving the pharmacokinetics of substrate
chemotherapeutic drugs, and in functional assays of BCRP activity for tailoring chemotherapy. In this study, a reversephase
high-performance liquid chromatographic method was developed for the determination of a simplified fumitremorgin
C analog, Ko134, a potent ABCG2 inhibitor, in murine serum. The assay involves a simple sample preparation
step followed by chromatographic separation on a C8 reversed-phase analytical column. The calibration plots were linear
over the range 0.1 to10 µg/ml (r > 0.99). The limits of detection and quantification were 10 ng/ml and 50 ng/ml, respectively.
The validation results demonstrated that the method is precise, accurate and selective for the determination of
Ko134 in mouse serum. The method was successfully applied to evaluate the pharmacokinetic parameters of Ko134 after
different modes of administration in mice.