Pharmacokinetics of ebeiedinone in mouse blood by UPLC–MS/MS

Abstract

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established to determine ebeiedinone in mouse blood, and the pharmacokinetics of ebeiedinone after intravenous (0.5 mg/kg) and oral (2, 4, and 8 mg/kg) administration was studied. Twenty-four mice were randomly divided into 4 groups, 1 group was for intravenous administration (0.5 mg/kg), and other 3 groups were for oral administration (2, 4, and 8 mg/kg), with 6 rats in each group. Yubeinine was used as an internal standard. Multiple reaction monitoring (MRM) mode was used to quantitatively analyzed ebeiedinone m/z 414.4 → 91.1 and the internal standard m/z 430.4 → 412.3 in the electrospray ionization (ESI) positive interface. In the concentration range of 1–2000 ng/mL, the ebeiedinone in the mouse blood was linear (r2 > 0.995), and the lower limit of quantification was 1.0 ng/mL. In the mouse blood, the intra-day precision coefficient of variation (CV) was less than 15%, and the inter-day precision CV was less than 15%. The accuracy ranged from 85.4% to 114.6%, and the average recovery was higher than 61.3%. The matrix effect was between 87.0% and 106.5%. These data met the pharmacokinetic study requirements of ebeiedinone. The UPLC–MS/MS method was sensitive, rapid, and selective and was successfully applied to the pharmacokinetic study of ebeiedinone in mice. The absolute bioavailability of ebeiedinone was 30.6%.

Natural drug sources for respiratory diseases from Fritillaria: chemical and biological analyses

“…It is necessary for researchers to conduct pharmacokinetics and pharmacodynamics, which will be beneficial for studying the action mechanism and developing the medicinal value of Bei Mu. A limited number of studies focused on pharmacokinetics and pharmacodynamics, such as the pharmacokinetics of ebeiedinone in mouse blood [ 132 ] and pharmacokinetic study of delavinone in mice [ 133 ].…”

“…Pharmacokinetic investigations by LC–MS focused on isosteroidal alkaloids (such as peimine, peiminine, verticine, verticinone and isoverticine, puqietinone, imperialine, delavinone, and ebeiedinone) in rat [ 173 – 177 ], mouse [ 132 , 133 ], and beagle dog [ 178 ]. Studies had also been conducted to investigate the tissue distribution and excretion of two components (peimine and peiminine) in rats on the basis of pharmacokinetics [ 179 ].…”

Pharmacokinetics and bioavailability of curdione in mice by UPLC-MS/MS

“…There were several LC-MS or LC-MS/MS methods developed for determination of curdione in rat or rabbit plasma [19][20][21][22][23][24], however, no UPLC-MS/MS method developed for determination of curdione in mice and its pharmacokinetics. Chromatographic detection methods have long analysis time, poor selectivity for complex matrices, low sensitivity, and cannot achieve effective detection of the drugs; UPLC-MS/MS due to its fast analysis speed, it has the advantages of high sensitivity and strong specificity [25][26][27][28][29][30]. In this study, the protein precipitation method was used to extract curdione in blood samples, and an UPLC-MS/MS method was established for the determination of curdione in mouse blood with high sensitivity and high specificity, and this method was successfully applied to the in vivo pharmacokinetics of curdione after gavage and intravenous injection in mice.…”