A simple UHPLC-MS/MS method for determination of SET2, a selective antagonist of TRPV2 receptor, in rat plasma...

Targeting the transient receptor potential vanilloid 2 channels (TRPV2) in order to alleviate or reverse the course of several diseases including multiple cancers, cardiovascular, immunological, or neurological disorders have been a matter of focus for several years now. SET2, a selective TRPV2 inhibitor, represents an innovative molecule which came into recognition in 2019 and seems to be a promising therapeutic modality in cancer and cardiac diseases. Drug discovery and bioanalysis in clinical environment demands simple, excellent, highly reliable, fast, sensitive, and selective analytical approaches which enable unambiguous identification and quantification of demanded molecule. Here, a targeted ultra-high-performance liquid chromatography - tandem mass spectrometry with electrospray ionization was developed for the quantification of SET2 in plasma samples. The developed method enabled analysis of approx. 15 samples within one hour. Simplicity of the whole analytical procedure can be emphasized by a very simple sample pretreatment based only on the protein precipitation with organic acid (here, 2 M tricholoroacetic acid). The validation procedure was characterized by promising validation parameters and excellent sensitivity what was documented by the limit of detection value at pg.mL^-1 concentration level. Analytical validation reported intra- and interday accuracy < 15 % for all quality control samples concentration levels. Similarly, excellent level of intra- (0.1 - 4.8 %) and interday (0.5 - 3.3 %) precision for the tested quality control samples was obtained. The applicability of the developed method was proven by quantifying SET2 concentration levels in plasma samples obtained from Wistar rats that were administered this drug intraperitoneally at a dose of 25 mg/kg. We expect that our new analytical method represents a very attractive tool that could be easily implemented in pharmacokinetics studies and/or therapeutic drug monitoring. Moreover, its applicability was confirmed by the new practicability evaluation metric tool.