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Abstract: Farfarae Flos, the dried flower buds of Tussilago farfara L., is usually used to treat coughs, bronchitic and asthmatic conditions as an important traditional Chinese medicine. Tussilagone and methl butyric acid tussilagin ester are seen as representatives of two kinds of active substances. In addition, the pyrrolizidine alkaloids, mainly senkirkine and senecionine, present in the herb can be hepatoxic. In this study, a rapid and sensitive ultra‐high‐performance liquid chromatography coupled with hybrid triple quadrupole time‐of‐flight mass spectrometry method was successfully applied to identify the metabolites of tussilagone, methl butyric acid tussilagin ester, senkirkine and senecionine. A total of 35, 37, 18 and nine metabolites of tussilagone, methl butyric acid tussilagin ester, senkirkine and senecionine in rats were tentatively identified. Hydrolysis, oxidation, reduction and demethylation were the major metabolic reactions for tussilagone and methl butyric acid tussilagin ester. The main biotransformation routes of senkirkine and senecionine were identified as demethylation, N‐methylation, oxidation and reduction. This study is the first reported analysis and characterization of the metabolites and the proposed metabolic pathways might provide further understanding of the metabolic fate of the chemical constituents after oral administration of Farfarae Flos extract in vivo. [ABSTRACT FROM AUTHOR]

Vindoline (VDL) is an indole alkaloid, possessing hypoglycemic and vasodilator effects, and it is also the prodrug of many vinca alkaloids. In this paper, we analyzed in vivo (including plasma, urine, bile and faeces) and in vitro metabolic profile of VDL in rat with ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). The chromatographic separation was performed on a C 18 column with a mobile phase consisted of 3 mM ammonium acetate buffer and acetonitrile at a flow rate of 300 μL/min. The mass spectral analysis was conducted in a positive electrospray ionization mode, and on-line data acquisition method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) were used in the biological samples analysis to trace all the potential metabolites of VDL. Twenty-five metabolites of VDL were detected by comparing with the blank sample, of which there were 2 sulfate conjugates. These data suggested that the biotransformation of VDL was deacetylation, oxidation, deoxidization, methylation, dealkylation and sulfate conjugation. This study provides useful information for further study of the pharmacology and mechanism of VDL, meanwhile, the research method can be widely applied to speculate structural features of the metabolites of other vinca alkaloids. [ABSTRACT FROM AUTHOR]

Although farrerol, a characteristically bioactive constituent of Rhododendron dauricum L., exhibits extensive biological and pharmacological activities (e.g., anti-oxidant, anti-immunogenic, and anti-angiogenic) as well as a high drug development potential, its metabolism remains underexplored. Herein, we employed ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with multiple data post-processing techniques to rapidly identify farrerol metabolites produced in vivo (in rat blood, bile, urine and feces) and in vitro (in rat liver microsomes). As a result, 42 in vivo metabolites and 15 in vitro metabolites were detected, and farrerol shown to mainly undergo oxidation, reduction, (de)methylation, glucose conjugation, glucuronide conjugation, sulfate conjugation, N-acetylation and N-acetylcysteine conjugation. Thus, this work elaborates the metabolic pathways of farrerol and reveals the potential pharmacodynamics forms of farrerol. [ABSTRACT FROM AUTHOR]

Eupatorin is the major bioactive component of Java tea (Orthosiphon stamineus), exhibiting strong anticancer and anti-inflammatory activities. However, no research on the metabolism of eupatorin has been reported to date. In the present study, ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) combined with an efficient online data acquisition and a multiple data processing method were developed for metabolite identification in vivo (rat plasma, bile, urine and feces) and in vitro (rat liver microsomes and intestinal flora). A total of 51 metabolites in vivo, 60 metabolites in vitro were structurally characterized. The loss of CH2, CH2O, O, CO, oxidation, methylation, glucuronidation, sulfate conjugation, N-acetylation, hydrogenation, ketone formation, glycine conjugation, glutamine conjugation and glucose conjugation were the main metabolic pathways of eupatorin. This was the first identification of metabolites of eupatorin in vivo and in vitro and it will provide reference and valuable evidence for further development of new pharmaceuticals and pharmacological mechanisms. [ABSTRACT FROM AUTHOR]

Highlights • The metabolites of hinokiflavone were first characterized. • A rapid and sensitive method was developed. • Glutamine conjugation and glycine conjugation were unique metabolic pathways of hinokiflavone. • The metabolic profiling of hinokiflavone was first inferred and summarized. Abstract Hinokiflavone (HF), belonging to biflavonoids, possesses excellent pharmacological activities, including anti-inflammatory, antioxidant and antitumor activity. Nevertheless, its metabolism in vivo (rats) and in vitro (rat liver microsomes and intestinal flora) is presently not characterized. In this study, ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) based on four-step strategy was a rapid method for the detection of HF metabolites. A total of 41 metabolites in vivo , 49 metabolites in vitro were characterized. It also verified that intestinal tract exceeds the liver in the biotransformation of HF. More significant, the main metabolic pathways for HF were mainly bio-transformed to various mono-flavone resulting from the rupture of connective C O bonds, which exhibited a large distinction with other biflavones. Noteworthily, glutamine conjugation and glycine conjugation were considered as unique metabolic pathways of HF. The information obtained from this study contributes to better understanding of pharmacological mechanism of HF. [ABSTRACT FROM AUTHOR]

Nevadensin is major constituents of Lysionotus pauciflorus Maxim . (Chinese name: Shidiaolan), which has a variety of pharmacological effects such as anti-mycobacterium tuberculosis activities, antitussive, anti-inflammatory and anti-hypertensive. In this paper, we investigated the metabolism of nevadensin in vitro and in vivo . A strategy was firstly developed to identify the metabolites of nevadensin by using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). An on-line data acquisition method a multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) was developed to trace all probable metabolites. Furthermore, some assistant tools, such as key fragment ions (KFI), were employed for compound hunting and identification. Based on the proposed method, 23 metabolites were structurally characterized in vivo including 16 phase I and 7 phase II metabolites, and 12 metabolites were detected in vitro containing 10 phase I and 2 phase II metabolites. The results indicated that oxidation, hydrolysis, demethylation, methylation, sulfate conjugation and glucuronide conjugation were main metabolic pathways of nevadensin. In a word, this study maybe can provide reference and valuable evidence for further investigation of the metabolic mechanism of nevadensin. [ABSTRACT FROM AUTHOR]

Sophoricoside (SOPH) is an isoflavone glycoside isolated from Fructus Sophorae , and it has the effects on reproductive system. Currently, a strategy was firstly developed to identify the metabolites of SOPH in vitro and in vivo using ultra high performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC–Q–TOF–MS/MS). Based on the proposed method, 60 metabolites were structurally characterized in vivo including 22 phase I and 38 phase II metabolites, and 4 metabolites in vitro were detected containing 2 phase I and 2 phase II metabolites. The results indicated that the metabolic pathways mainly included oxidation, reduction, hydrolysis, methylation, sulfate, glucuronide, glutamine and glycine conjugation. These results will provide basic data for future pharmacological and toxicology studies of SOPH and other isoflavone glycoside. [ABSTRACT FROM AUTHOR]