Simultaneous Determination of Twenty-Five Compounds in Rat Plasma Using Ultra-High Performance Liquid Chromatography-Polarity Switching Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study

Abstract

An attempt was made to characterize the pharmacokinetic profiles of Qishen Keli (QSKL) that has been widely proved to be effective in clinical practice. A method using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of 25 analytes in rat plasma was developed and validated. Satisfactory chromatographic separation was achieved on an ACQUITY UPLC HSS T3 column with gradient elution using mobile phase consisting of 0.02% aqueous formic acid (A) and acetonitrile fortified with 0.02% formic acid (B), and analyte detection was carried out using polarity-switching multiple reaction monitoring mode. Method validation assays in terms of selectivity, linearity, inter- and intra-day variations, matrix effect, and recovery demonstrated the newly developed method to be specific, sensitive, accurate, and precise. Following the oral administration of QSKL at a single dose, the qualified method was successfully applied for pharmacokinetic investigations in sham and model rats. Mild differences occurred for the pharmacokinetic patterns of most components between those two groups, whereas significant differences were observed for glycyrrhizic acid and glycyrrhetic acid. The obtained findings could provide meaningful information for the clarification of the effective material basis of QSKL.

Protective effects of 18β‐Glycyrrhetinic acid against myocardial infarction: Involvement of PI3K/Akt pathway activation and inhibiting Ca2+ influx via L‐type Ca2+ channels

“…Licorice is a widely used herb that exists worldwide and has important pharmacological effects (Somayeh et al, 2017;Wittschier et al, 2009). Some of the ingredients in licorice have been shown to improve heart function (Najuan et al, 2011;Zhang et al, 2017). Oxidative stress induces excessive proliferation of ROS, which leads to cell apoptosis and even myocardial injury (Tian et al, 2017).…”

“…Licorice is a widely used herb that exists worldwide and has important pharmacological effects (Somayeh et al., 2017 ; Wittschier et al., 2009 ). Some of the ingredients in licorice have been shown to improve heart function (Najuan et al., 2011 ; Zhang et al., 2017 ).…”

Decomposing the Mechanism of Qishen Granules in the Treatment of Heart Failure by a Quantitative Pathway Analysis Method

“…These granules are used for warming Yang, nourishing Qi, promoting blood circulation to remove stasis, heat-clearing, and detoxification. As shown in our previous studies, some active compounds of QSG including luteolin, cryptotanshinone, licochalcone A, glycyrrhetinic acid, salsolinol, isoacid chlorogenic C, salvianolic acid A, and salvianolic acid B, which all have been validated by direct biochemical methods [ 13 , 14 ]. Furthermore, QSG prevents the development of myocardial hypertrophy and fibrosis, by multiple pharmacological mechanisms, in the midst of heart failure induced by chronic myocardial ischemia, myocardial infarction, and an excessive afterload [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

Multiple component‐pharmacokinetic studies on 10 bioactive constituents of Peiyuan Tongnao capsule using parallel reaction monitoring mode

“…The systematic study of the pharmacokinetics of TCM is helpful to elucidate the pharmacodynamic basis and mechanism of TCM, which can provide a reference for the quality control (QC) of TCM (Hashida, 2020;Zeng et al, 2021;Zhang et al, 2018). As we all know, the therapeutic effects of TCM are usually based on the overall synergy of multiple ingredients (Liu et al, 2016(Liu et al, , 2019Zhang et al, 2017). The pharmacokinetic et al, 2019).…”