Simultaneous determination of cordycepin and its metabolite 3′‐deoxyinosine in rat whole blood by ultra‐high‐performance liquid chromatography coupled with Q Exactive hybrid quadrupole orbitrap high‐resolution accurate mass spectrometry and its application to accurate pharmacokinetic studies

Abstract

Funding information "Chen Guang" project supported by Shanghai Municipal EducationCordycepin from Cordyceps possesses excellent pharmacological properties, including anti-inflammation and anti-tumor effects, therefore representing a potential alternative medicine. However, doubts about the pharmacokinetic results of cordycepin had been raised in the previous study due to its rapid deamination. The organic solvent methanol was immediately added to terminate the degradation of cordycepin in anticoagulated blood samples and enable the accurate evaluation of pharmacokinetics in vivo. A sensitive and selective ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry method was developed and validated to simultaneously determine cordycepin and its deamination metabolite 3′-deoxyinosine using 2-chloroadenosine as an internal standard in rat whole blood. The calibration curves of cordycepin and 3′-deoxyinosine showed excellent linearity within the concentration range of 1.05-10 000.00 ng/ml with acceptable accuracy, precision, selectivity, recovery, matrix effect, and stability. This method was successfully applied to the

Ultra‐high‐performance liquid chromatography‐Quadrupole‐Exactive‐Orbitrap‐tandem mass spectrometry‐based putative identification for Eucommiae Folium (Duzhongye) and its quality‐marker candidate for pharmacopeia

“…In addition, isoquercitrin ( 14) exhibited high pharmacological relevance. According to previous reports, isoquercitrin (14) shows similar pharmacological effects to Eucommiae Folium [34][35][36][37][38][39][40], especially the antihypertensive effect [41]. Although the old Q-marker chlorogenic acid also shows anti-hypertensive activity [3,42] (Table 1, entry 3), the molecular docking data indicated that the new Q-marker isoquercitrin played a more important role than chlorogenic acid for the structure advantage [41].…”

“…All bioactive compounds were putatively identified and listed in Figure 4. For the convenience of reading, the MS spectra and fragment elucidation of three bioactive compounds were respectively illustrated in Figures 5-7, including chlorogenic acid (3), isoquercitrin (14), and pinoresinol (11). As shown in Figure 3, the identified bioactive compounds (1-26) can be classified into six main types, i.e., flavonoid derivatives, caffeoylquinic acids, alkaloids, lignans, xanthones, and steroids.…”

“…Likewise, dihydrokaempferol may be biosynthesized into quercetin (21) by F3'H and FLS [30]. Quercetin (21) undergoes glycosidation at different sites, to give quercetin 3-gentiobioside (4), quercetin 3-O-β-Dglucose-7-O-β-D-gentiobioside (5), hyperoside (12), rutin (13), isoquercitrin (14), quercetin-3-O-β-D-xylopyranoside (15), quercitrin (18), and quercetin (21), respectively. If 3′-OH methylation, quercetin (21) can also be converted into isorhamnetin-3-O-β-D-glucoside (19).…”

“…Usually, the UHPLC-Quadrupole-Exactive-Orbitrap MS/MS can simultaneously identify dozens or even hundreds of compounds [12][13][14][15]. Its efficiency is much higher than the conventional high-performance liquid chromatography coupled with ultraviolet-visible spectroscopy (HPLC-UV) analysis, which can only simultaneously identify 4-8 compounds in Eucommiae Folium [9,10,16,17].…”

Cordycepin: A review of strategies to improve the bioavailability and efficacy

“…Deamination metabolism of cordycepin by ADA in rat whole blood, plasma, and hematocyte was investigated by Qi et al (2023) and found the t 1/2 of cordycepin in the whole blood, plasma, and hematocyte of rat was 15.82, 159.17, and 24.37 min, respectively, at the same protein concentration. And the activity of ADA in rat whole blood, plasma, and hematocyte determined by the production of 3′‐deoxyinosine was 1.8 ± 0.04, 0.4 ± 0.1, and 2.2 ± 0.2 unit/mg protein, respectively.…”