Chemical UPLC‐ESI‐MS/MS profiling of aconitum alkaloids and their metabolites in rat plasma and urine after oral administration of Aconitum carmichaelii Debx. Root extract

Abstract

In this paper, an ultra high performance liquid chromatography tandem mass spectrometric (UPLC-ESI-MS/MS) method in positive ion mode was established to systematically identify and to compare the major aconitum alkaloids and their metabolites in rat plasma and urine after oral administration of Fuzi extract. A total twenty-nine components including twenty-five C19-diterpenoid alkaloids and four C20-diterpenoid alkaloids were identified in Fuzi extract. Thirteen of the parent components and five metabolites were detected in rat plasma and sixteen parent compounds and six metabolites in urine. These parent components found in rat plasma and urine were mainly C19-diterpenoid alkaloids. All of the metabolites in vivo were demethylated metabolites (phase I metabolites), which suggested that demethylation was the major metabolic pathway of aconitum alkaloids in vivo. A comparison of the parent components in rat plasma and urine revealed that 3-deoxyacontine was found in plasma but not in urine, while kalacolidine, senbusine and 16-β-hydroxycardiopetaline existed in urine but not in plasma, which indicated that most alkaloids components were disposed and excreted in prototype form. This research provides some important information for further metabolic investigations of Fuzi in vivo.

Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics

“…After combining the results of the S-plots, the VIP value (VIP >1) was obtained from OPLS-DA analysis, and the corresponding metabolites could be selected. The chemical structures of the metabolites were identified using online databases such as SciFinder (https://scifinder.cas.org/), and further confirmation was obtained through comparisons with authentic standards and published literature (Wang et al, 2002;Yue et al, 2007;Hu et al, 2009;Yan et al, 2010;Sun et al, 2012;Zhang et al, 2012;Sun et al, 2013;Xu et al, 2014;Yang et al, 2014;Luo et al, 2016;Zhang et al, 2017;Lei et al, 2021). A total of 42 discriminating metabolites were tentatively identified, and the detailed information is given in Table 2 and Supplementary Figure S2.…”

Identification and quantification of eight alkaloids in Aconitum heterophyllum using UHPLC‐DAD‐QTOF‐IMS: A valuable tool for quality control

“…Various gradient elutions were applied for clear separation of targeted alkaloids by different research groups. A gradient from 95% (A) at 0 min to 2% (A) at 30 min and back to 95% (A) at the end of the run was employed by Chen et al 43 A gradient of 20% B at 0–4 min, 25% B at 4–10 min, 90% B at 10.01–12 min, and back to 20% B at 12.01–15 min was used by He et al 24 A gradient of 20% B at 0–2 min, 16% B at 2–3.8 min, 22% B at 6 min, 35% B at 9 min, 55% B at 9.5 min, and 100% B at 13 min was used by Gao et al 26 A gradient of 50% B at 0–0.5 min, 50–75% B at 0.5–5 min, 95% B at 5–10 min, and 95% B at 10–12 min was employed for separation by Liang et al 44 Based on the above gradient phases, initially we used 0.1% formic acid in water and 0.1% formic acid in acetonitrile with a gradient of 70% A at 0–4 min, 50% A at 6 min, 65% A at 14 min, and 70% A at 16 min. This run showed some initial separation but could not replicate the results after a few runs.…”

“…Aconitum lipo-alkaloids were identified and quantified using HPLC coupled with electrospray ionization (ESI)-MS via heating of aconitine, mesaconitine, and hypaconitine with corresponding fatty acids. 26 An ultra-flow liquid chromatography (UFLC)-ESI-MS-based method was developed for the separation of marker alkaloids (higenamine, benzoylhypaconitine, benzoylmesaconitine, benzoylaconitine, aconitine, hypaconitine, and mesaconitine). In another study, three alkaloids and seven ginsenosides were resolved to develop a common method for rapid resolution liquid chromatography (RRLC)-triple quadrupole (QQQ)-MS/MS.…”

“…For example, Jabeen et al 25 determined the aconitine concentration in Aconitum chasmanthum and A. heterophyllum using a reversed phase HPLC‐UV‐diode array detector (DAD) method. Aconitum lipo‐alkaloids were identified and quantified using HPLC coupled with electrospray ionization (ESI)‐MS via heating of aconitine, mesaconitine, and hypaconitine with corresponding fatty acids 26 . An ultra‐flow liquid chromatography (UFLC)‐ESI‐MS‐based method was developed for the separation of marker alkaloids (higenamine, benzoylhypaconitine, benzoylmesaconitine, benzoylaconitine, aconitine, hypaconitine, and mesaconitine).…”

The effect of compatibility of Aconiti Radix and honey on the pharmacokinetics of five Aconitum alkaloids in rat plasma

“…DDAs include hypaconitine (HA), mesaconitine (MA), and aconitine (AC). MDAs include benzoylhypaconine, benzoylmesaconine (BMA), and benzoylaconine (BAC) (You et al, 2022; Zhang et al, 2018). The efficacy of MDAs is similar to that of DDAs; however, the toxicity of MDAs is much lower than that of DDAs (Singhuber et al, 2009; Wu et al, 2018).…”