Evaluating Pharmacokinetic and Distribution Characteristics for A New Antitumor Activity Ortho-aryl Chalcone Compound of OC26 in Rats by LC-MS/MS Method

Abstract

Introduction: OC26, an ortho-aryl chalcone compound, shows excellent antitumor activity in vitro and vivo. However, the pharmacokinetic characteristics of OC26 have not been comprehensively reported. It is essential to investigate the correlation of pharmacological response. Objective: To further explore OC26, this study aims to develop an ultra-performance liquid chromatography- tandem mass spectrometric (UPLC-MS/MS) method to reveal the pharmacokinetics and distribution characteristics in rats of OC26. Methods: An UPLC-MS/MS method was developed to detect OC26 in plasma and various tissues. The protein precipitation method was applied to process the biological samples. After intravenous injection 12.5mg/kg of OC26 in rats, plasma and tissue samples were collected from rats and the method was applied to investigate pharmacokinetic and distribution characteristics of OC26. Results: Calibration curve samples of OC26 concentration range from 20 to 2000 ng/mL with the goodness of fit (r2> 0.99). The precisions for the method were within 12.3%, while the accuracies for the method were within ±11% (bias). The matrix effect had no influence on the accuracy and precision of the method. After intravenous injection 12.5mg/kg of OC26 in rats, OC26 was rapidly eliminated (t1/2=31.39±7.87min, MRT0→∞=15.03±2.55min) from rat plasma and widely distributed (Vd=4.83±0.96L/kg) in tissues. The highest concentration of OC26 was detected in the brain in which peak content (~8962.78ng/g at 15min) was over 5-fold higher than that of in other tissues, which prompted new potential targets in the brain. Besides, lung and heart also detected quite a high level of OC26. Benefited from quick elimination in the collected tissues and plasma, long-term accumulation was not observed as chronic toxicity might be less. Conclusions: This UPLC-MS/MS method was successfully applied to detect OC26 and provide a theoretical basis for the further study of OC26.