Determination and Pharmacokinetics of Okanin in Rat Plasma by UltraHigh Performance Liquid Chromatography Coupled with Triple-Quadrupole Tandem Mass Spectrometry.

Yurui Shi,Ning Zhang,Meizhu Zheng,Rongda Chen,Guiming Liu,Li Li,Jing Xie

doi:10.1155/2020/4247128

Abstract

Okanin is a major flavonoid found in Coreopsis tinctoria Nutt., arousing huge interest recently for its considerable biological characteristics including antioxidant, antineurotoxic, and antidiabetic activities. An ultrahigh performance liquid chromatography triple-quadrupole tandem mass spectrometry (UPLC-MS) was successfully used to determine okanin in rat plasma after oral administration of okanin. Bavachalcone acted as an internal standard (IS). By gradient elution, IS and analyte were separated on a C18 column for 7 min at a flow rate of 0.25 mL/min with acetonitrile-0.1% acetic acid mobile phase. The stability, matrix effect, extraction recovery, accuracy, precision, linearity, and selectivity of the method were firstly demonstrated. The major pharmacokinetic parameters of okanin in rat plasma were then measured using the developed UPLC-MS method. An UPLC-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was finally established to obtain the specific and accurate mass of okanin in rat plasma after oral administration, and its proposed fragmentation was further elaborated.

Highlights

In China, Coreopsis tinctoria Nutt.’s (C. tinctoria) capitula is consumed as herbal tea, and its extracts exhibit various biological activities including antioxidant [1,2,3,4], antihypertensive [5, 6], antineuroinflammatory [7], antidiabetic activities [8,9,10,11], hepatic insulin resistance [12], and antihyperlipidemic effects [13]
In order to study the possible endogenous interference on okanin and internal standard (IS), the blank plasma from six rats, the corresponding blank plasma added with okanin and IS, and the plasma of rats after oral administration of okanin were analyzed by UPLC-MS/MS, respectively. e retention times (Rt) and Multiple reaction monitoring (MRM) transitions were adopted for analyzing okanin and IS
Intraday and interday accuracy and precision were assessed from replicate analyses (n 6) of low, middle, and high concentrations of quality control (QC) samples in the same day and over three consecutive days, respectively. e concentration of sample was calculated according to the standard curve equation prepared on the same day. e precision of the method was calculated as the relative standard deviation (RSD) and was less than 15%

Summary

Introduction

In China, Coreopsis tinctoria Nutt.’s (C. tinctoria) capitula is consumed as herbal tea, and its extracts exhibit various biological activities including antioxidant [1,2,3,4], antihypertensive [5, 6], antineuroinflammatory [7], antidiabetic activities [8,9,10,11], hepatic insulin resistance [12], and antihyperlipidemic effects [13]. Okanin refers to a major flavonoid found in C. tinctoria [14] having attracted considerable attention for its potential contribution to the pharmacological activity of C. tinctoria. Okanin showed a better antioxidant activity than quercetin in cellular experiments with IC50 as 11.0 μM [15]. Kil et al reported that okanin inhibited the production of nitric oxide and the expression of inducible nitric oxide synthetase in macrophages activated by lipopolysaccharides via nuclear factor-erythroid 2related factor 2-dependent heme oxygenase-1 expression [16]. Okanin could significantly inhibit α-glucosidase with IC50 values about 0.02 mM, suggesting that it is a potential drug for the treatment of diabetes [17]. Okanin showed significant anti-neuroinflammatory activity with the IC50 value at 15.54 μM, suggesting that it can treat neurodegenerative diseases [7]

Methods

Results

Conclusion