Ultra performance liquid chromatography coupled with electrospray and atmospheric pressure chemical ionization (ESCi)‐quadrupole time‐of‐flight mass spectrometry with novel mass spectrometry^{Elevated Energy} (MS^E) data collection technique: Determination and pharmacokinetics, tissue distribution and biliary excretion study of ergone in rat

Abstract

Ergosta-4,6,8(14),22-tetraen-3-one (ergone) has been proved to have novel antitumor effects on HepG2 cells. The aim of this study was to investigate the pharmacokinetics, tissue distribution, and biliary excretion of ergone in rats following a single oral administration (5, 10, and 20 mg/kg). The levels of ergone in plasma, tissues, and bile were measured by ultra performance liquid chromatography coupled with electrospray and atmospheric pressure chemical ionization (ESCi)-quadrupole time-of-flight mass spectrometry with novel mass spectrometry(Elevated Energy) (MS(E)) data collection technique method. The results show ergone was distributed and eliminated from rat plasma and in non-linear pharmacokinetics from a dose range of 5-20 mg/kg. The ergone was found to distribute widely in the internal organs, with tissue concentrations in order of lungs, spleen, liver, intestine, kidneys, heart, stomach, parorchis, teasticles, and brain. At 12 h after dosing, the tissue concentrations in the organs were markedly decreased. The lungs, spleen, and liver were the dominant organs with high tissue concentrations that might be the primary sites for metabolism and elimination of ergone. Total recoveries of ergone within 24 h in bile were 34.14%.

A Pharmaco-Metabonomic Study on Chronic Kidney Disease and Therapeutic Effect of Ergone by UPLC-QTOF/HDMS

“…Our previous study demonstrated that ergone could prevent progression of renal injury and subsequent renal fibrosis [21] . Pharmacokinetic studies indicated ergone was mainly excreted into the rat feces via bile instead of urine with approximately 57% of the loading dose present in the feces within 24 h [22] – [25] . Although therapeutic efficacy of ergone for CKD was demonstrated, the biochemical mechanism of its action was still not fully understood.…”

Structure and Biological Activity of Ergostane-Type Steroids from Fungi

“…The following pharmacokinetic parameters were measured after a single oral administration (20 mg/kg) of ergone to rats: the area under the plasma concentration versus time curve from time 0 h to indefinite time (AUC 0–∞ ) was 19.6 μg h mL −1 , peak plasma concentration (C max ) was 1.5 μg/mL, the elimination half-life (t 1/2 ) was 5.90 h, and time to C max (T max ) was 3.8 h [ 266 ].…”

Identification of metabolites of palmatine in rats after oral administration using ultra‐high‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry

“…In general, the UPLC technique is combined with high‐resolution mass spectrometry (HRMS) for metabolite identification in vitro or in vivo . Quadrupole time‐of‐flight mass spectrometry (QTOF‐MS), a HRMS technique, allows the generation of mass information with higher accuracy and precision for the identification of known or unknown compounds, which could provide candidate empirical formulae with a mass error of less than 5 ppm . Accordingly, the Waters QTOF mass spectrometer was able to generate accurate mass data which could be used to calculate elemental compositions of metabolites or their fragment ions .…”