Development of a UPLC-MS/MS method for determination of a dual EZH1/2 inhibitor UNC1999 in rat plasma

Aim: We aimed to establish and validate a simple and sensitive UPLC-MS/MS method for the determination of UNC1999, a dual inhibitor against EZH1 and EZH2 in plasma samples. Materials & methods: UNC1999 in rat plasma was processed with protein precipitation method and then separated on a C-18 column and detected under positive ionization mode. The method presented good linearity over the range of 1.0-2000 ng/ml with good accuracy and precision. UNC1999 was absorbed slowly and achieved a maximum concentration of 118.8 +/- 12.0 ng/ml 1.5 h after oral administration. Conclusion: The method provides a favorable character in selectivity, linearity, accuracy, precision, recovery, matrix effects and stabilities and was suitable for describing the pharmacokinetic profile of UNC1999.

Automated summary

The aim of this study was to establish and validate a simple and sensitive UPLC-MS/MS method for determining the concentration of UNC1999 in plasma samples. The method showed good linearity, accuracy, and precision, and allowed for the characterization of the pharmacokinetic profile of UNC1999 in rats.