Characterization of lignans in Forsythiae Fructus and their metabolites in rats by ultra-performance liquid chromatography coupled time-of-flight mass spectrometry

2020 ◽  
Author(s):  
Feng-xiang Zhang ◽  
Zi-ting Li ◽  
Chang Li ◽  
Min Li ◽  
Zhi-hong Yao ◽  
...  
Keyword(s):  
Ring Opening ◽  
Furan Ring ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Chemical Information ◽  
Flight Mass Spectrometry ◽  
Blood And Urine Samples ◽  
Metabolic Reactions ◽  
First Time

Abstract Objectives This study was designed to profile the chemical information of Forsythiae Fructus (FF) and investigate the in-vivo FF-related xenobiotics, especially for lignans. Methods Rats were oral administrated of FF and pinoresinol-4-O-glucoside, respectively. Blood and urine samples were collected after ingestion, and xenobiotics was profiled by an UPLC/Qtof MS method. Key findings A total of 19 lignans were identified or tentatively characterized in FF, and 63 lignan-related xenobiotics were found in rat plasma and urine after ingestion of FF. It was found that lignans could be transformed into metabolites by furan ring opening, hydrogenation, demethylation, dehydration and phase II reactions (sulfation and glucuronidation). The whole metabolic behaviour of bisepoxylignan was revealed by evaluating the metabolism of pinoresinol-4-O-glucoside in vivo. It was found that the configuration of C-8/C-8ʹ was retained after furan ring opening and metabolic reactions always occurred at position of C-3/C-4/C-5 or C-3ʹ/C-4ʹ/C-5ʹ. Additionally, other types components in FF and in vivo were also characterized. Conclusions This work revealed the in-vivo metabolism of FF, and reported the characteristic metabolic reactions of lignans for the first time. It was also provided the foundation for the further investigation on pharmacodynamic components of FF or TCMs containing FF.

scholarly journals Metabolic Profiling of Alpinetin in Rat Plasma, Urine, Bile and Feces after Intragastric Administration

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3458
Author(s):  
Jieying Qiu ◽  
Hongyu Wu ◽  
Feng Feng ◽  
Xiaoying He ◽  
Caihong Wang ◽  
...  
Keyword(s):  
Formic Acid ◽  
High Strength ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Intragastric Administration ◽  
Flight Mass Spectrometry ◽  
Metabolic Reactions ◽  
First Time

Alpinetin, a bioactive flavonoid, has been known to have a diverse therapeutic effect, with namely anti-inflammatory, anticancer and antioxidant effects with low systemic toxicity. This study aimed to obtain metabolic profiles of alpinetin in orally administrated rats. The metabolites of alpinetin were systematically analyzed and identified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The chromatographic separation was achieved on a High Strength Silica (HSS) T3 (1.8 μm, 2.1 × 100 mm) column with the mobile phase consisting of water containing 0.1% formic acid and acetonitrile with 0.1% formic acid via gradient elution. An extracted ion chromatogram strategy based on multiple prototype/metabolite intermediate templates and 71 typical metabolic reactions was proposed to comprehensively profile the metabolites of alpinetin. With the metabolite profiling strategy, altogether 15 compounds were recognized from urine, plasma, bile and feces of rats after intragastric administration of alpinetin for the first time. The prototype, glucuronide conjugates and phenolic acids metabolites were the probable predominant form of alpinetin in rats. This work showed a comprehensive study of the probable metabolic pathways of alpinetin in vivo, which could provide meaningful information for future pharmacological studies.

scholarly journals Profiling and Pharmacokinetic Studies of Alkaloids in Rats After Oral Administration of Zanthoxylum nitidum Decoction by UPLC-Q-TOF-MS/MS and HPLC-MS/MS

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 585 ◽  
Author(s):  
Aihua Huang ◽  
Yuguang Chi ◽  
Jiawei Liu ◽  
Mincun Wang ◽  
Jialiang Qin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Oral Administration ◽  
High Performance ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Flight Mass Spectrometry ◽  
Zanthoxylum Nitidum

Zanthoxylum nitidum (Roxb.) DC (Rutaceae), called as “liangmianzhen” in China, is well known for its anti-inflammation and analgesic effect. Alkaloids are its main active constituents. However, little has been known about the absorption of main alkaloids in vivo. In this study, an ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was employed for identification of absorbed alkaloids in rats after oral administration of Z. nitidum decoction. By analyzing the fragmentation patterns, a total of nineteen alkaloids were exactly or tentatively identified in rat plasma after treatment, of which magnoflorine, α-allocryptopine, and skimmianine are dominant. Moreover, a high performance liquid chromatography coupled mass spectrometry method was developed for simultaneous quantification of magnoflorine, α-allocryptopine, and skimmianine, and successfully applied to pharmacokinetic study in rats after oral administration of Z. nitidum decoction. The research would contribute to comprehensive understanding of the material basis and function mechanism of Z. nitidum decoction.

Metabolic profile of dendrobine in rats determined by ultra-high performance liquid chromatography/Quadrupole time-of-flight mass spectrometry

2020 ◽  
Vol 23 ◽  
Author(s):  
Jun-qi Bai ◽  
Qian-xiang Guo ◽  
Jing Zhang ◽  
Juan Huang ◽  
Wen Xu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Metabolite Profiling ◽  
High Performance ◽  
Time Of Flight ◽  
Fragmentation Pathway ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Flight Mass Spectrometry

Aims & Objective: Dendrobine is a major alkaloid present mainly in dendrobium nobile Lindl. It has been reported to have analgesic, antipyretic, lower heart rate and blood pressure and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. Methods: In this study, the in vivo metabolite profiling of dendrobine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilotTM software with mass defect filter (MDF) technique. These predicted metabolites were further analyzed by MS2 spectra, and compared with the detailed fragmentation pathway of the dendrobine standard and literature data. Results: total of 59 metabolites were identified for the first time in rat plasma and urine after oral administration of dendrobine. Demethylated, dehydrogenated, hydroxylated, ketonizated and glucuronide were the major metabolic pathways. Conclusions: This research provides scientific and reliable support for full understanding of the metabolic fate of dendrobine in vivo.

scholarly journals A Metabolomic Strategy to Screen the Prototype Components and Metabolites ofShuang-Huang-Lian Injectionin Human Serum by Ultra Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Mingxing Guo ◽  
Baosheng Zhao ◽  
Haiyu Liu ◽  
Li Zhang ◽  
Long Peng ◽  
...  
Keyword(s):  
Human Serum ◽  
Human Body ◽  
Matrix Effects ◽  
Ultra Performance Liquid Chromatography ◽  
Acute Respiratory Tract Infection ◽  
Chemical Compositions ◽  
Drug Induced ◽  
Flight Mass Spectrometry ◽  
Chinese Patent ◽  
Metabolic Reactions

Shuang-huang-lian injection(SHLI) is a famous Chinese patent medicine, which has been wildly used in clinic to treat acute respiratory tract infection, pneumonia, influenza, and so forth. Despite the widespread clinical application, the prototype components and metabolites ofSHLIhave not been fully elucidated, especially in human body. To discover and screen the constituents or metabolites of Chinese medicine in biofluids tends to be more and more difficult due to the complexity of chemical compositions, metabolic reactions and matrix effects. In this work, a metabolomic strategy to comprehensively elucidate the prototype components and metabolites ofSHLIin human serum conducted by UPLC-Q-TOF/MS was developed. Orthogonal partial least squared discriminant analysis (OPLS-DA) was applied to distinguish the exogenous, namely, drug-induced constituents, from endogenous in human serum. In the S-plot, 35 drug-induced constituents were found, including 23 prototype compounds and 12 metabolites which indicated thatSHLIin human body mainly caused phase II metabolite reactions. It was concluded that the metabolomic strategy for identification of herbal constituents and metabolites in biological samples was successfully developed. This identification and structural elucidation of the chemical compounds provided essential data for further pharmacological and pharmacokinetics study ofSHLI.

scholarly journals An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2894 ◽  
Author(s):  
Song-Tao Dong ◽  
Ying Li ◽  
Hao-Tian Yang ◽  
Yin Wu ◽  
Ya-Jing Li ◽  
...  
Keyword(s):  
Matrix Effects ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Analysis Method ◽  
T790m Mutation ◽  
Flight Mass Spectrometry ◽  
Relative Standard ◽  
New Generation ◽  
Tof Ms

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.

scholarly journals In Vitro/In Vivo Metabolism of Ginsenoside Rg5 in Rat Using Ultra-Performance Liquid Chromatography/Quadrupole-Time-of-Flight Mass Spectrometry

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2113 ◽  
Author(s):  
Chao Hong ◽  
Ping Yang ◽  
Shuping Li ◽  
Yizhen Guo ◽  
Dan Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Time Of Flight ◽  
Ultra Performance Liquid Chromatography ◽  
In Vivo Metabolism ◽  
Rat Urine ◽  
Flight Mass Spectrometry ◽  
Ginsenoside Rg5

Background: Ginsenoside Rg5 has been proved to have a wide range of pharmacological activities. However, the in vitro and in vivo metabolism pathways of ginsenosides are still unclear, which impedes the understanding of their in vivo fate. In this paper, the possible metabolic process of Rg5 was studied and the metabolites are identified. Methods: Samples from rat liver microsomes (RLMs) in vitro and from rat urine, plasma and feces in vivo were collected for analysis after oral administration of Rg5. A rapid analysis technique using ultra-performance liquid chromatography (UPLC)/quadrupole-time-of-flight mass spectrometry (QTOF-MS) was applied for detecting metabolites of Rg5 both in vitro and in vivo. Results: A feasible metabolic pathway was proposed and described for ginsenoside Rg5. A total of 17 metabolic products were detected in biological samples, including the RLMs (four), rat urine (two), feces (13) and plasma (four). Fifteen of them have never been reported before. Oxidation, deglycosylation, deoxidation, glucuronidation, demethylation and dehydration were found to be the major metabolic reactions of Rg5. Conclusions: The present study utilized a reliable and quick analytical tool to explore the metabolism of Rg5 in rats and provided significant insights into the understanding of the metabolic pathways of Rg5 in vitro and in vivo. The results could be used to not only evaluate the efficacy and safety of Rg5, but also identify potential active drug candidates from the metabolites.

Rapid screening of active components group with Topoisomerase I inhibitory activity in Sophora alopecuroides L. based on ultrafiltration coupled with UPLC-QTOF-MS

2021 ◽  
Vol 22 ◽  
Author(s):  
Lin Zhang ◽  
Xiaoying Yin ◽  
Xi Wan ◽  
Yun Sun ◽  
Menghui Cao ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Topoisomerase I ◽  
Molecular Mechanisms ◽  
Ultra Performance Liquid Chromatography ◽  
Rapid Screening ◽  
Active Components ◽  
Pharmacological Mechanism ◽  
Flight Mass Spectrometry ◽  
Sophora Alopecuroides

Background: Topoisomerase I (Topo I) is a key target of many antitumor drugs in vivo. Alkaloids in Sophora alopecuroides L. can reportedly inhibit Topo I activity, but the pharmacodynamic material basis has not yet been determined. Objective: The objective of this study is to rapidly identify active components group which inhibit Topo I in S. alopecuroides L. Methods: Affinity ultrafiltration-ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UF-UPLC-QTOF-MS) screening system based on Topo I protein was established to screen and isolate a total alkaloid fraction in S. alopecuroides L. Topo I inhibitory activity and anti-tuomor proliferation activity of the screened components were evaluated, and their molecular mechanisms were studied. Results: Six compounds bound specifically to Topo I were obtained. Further screening showed that matrine, cytisine, and sophoridine presented higher inhibitory activity on Topo I and were able to inhibit the proliferation of breast cancer MDA-MB-468 cells with IC50 values of 9.40 ± 1.12 mM, 17.4 ± 2.20 mM and 10.4 ± 1.37 mM, respectively. To the best of our knowledge, their dual molecular mechanisms against Topo I have been discussed here for the first time: (1) stabilization of Topo I-DNA complex and (2) inhibition or blocking of Topo I binding to DNA. Conclusion: Matrine, cytisine, and sophoridine from S. alopecuroides L. were defined as the active components group with Topo I inhibitory activity and their pharmacological mechanism was confirmed, which provided an important base for further research and development of antitumor components fromS. alopecuroides L.

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