Characterization of the In Vivo and In Vitro Metabolites of Linarin in Rat Biosamples and Intestinal Flora Using Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry

Feng, Xinchi; Yang, Li; Guang, Chenxi; Qiao, Miao; Wang, Tong; Chai, Liwei; Qiu, Feng

doi:10.3390/molecules23092140

Cited by 29 publications

(16 citation statements)

References 20 publications

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“…The corresponding ESI-MS 2 spectrum featured product ions with m/z 281.0782, 255.0997, and 253.0843 produced by loss of H 2 O, CO 2 , and H 2 O + CO, respectively, while the product ion with m/z 205.0483 was formed through C2–C1′ bond cleavage. Additionally, secondary ions with m/z 179.0333 and 119.0493 were produced by retro-Diels−Alder (RDA) cleavage of ring C, and this reaction was concluded to be a representative flavonoid fragmentation pathway allowing rapid metabolite identification [21,27,28]. The MS/MS spectra and fragmentation pathways of farrerol are presented in Figure 3.…”

Section: Resultsmentioning

confidence: 99%

“…The two major product ions with m/z 285.0760 and 269.0800 were ascribed to loss of CO and CO 2 , respectively [30]. RDA cleavage afforded ions with m/z 193.0121 (Δ = 14 Da) and 119.0495 [21]. Based on the above, M15 and M16 were identified as 8-ketofarrerol and 6-ketofarrerol, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) is widely employed for the rapid and accurate qualitative analysis of biological samples [21], as exemplified by the popularity of using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) for metabolite identification [21,22]. Therefore, these popular technologies were herein chosen to probe farrerol metabolism.…”

Section: Introductionmentioning

confidence: 99%

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A Complete Study of Farrerol Metabolites Produced In Vivo and In Vitro

Yin

Ma²,

Liang

et al. 2019

Molecules

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Complete Study of Farrerol Metabolites Produced In Vivo and In Vitro

Yin

Ma²,

Liang

et al. 2019

Molecules

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“…It was observed from the concentration–time curve that tenacissoside B, I, H and G had double peaks, which might be associated with enterohepatic and enteric circulation (Feng et al, 2018; Wang, Bao, Wang, Li, & Meng, 2019). Those pharmacokinetic profiles suggested that the maximal concentrations of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, tenacissoside B, I and G were apparently achieved after 0.25 and 0.5 h for tenacissoside H, revealing that these analytes were rapidly absorbed in rat blood.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous determination of eight bioactive components in Marsdenia tenacissima extract in rat plasma by LC–MS/MS and its application in a pharmacokinetic study

Pei

Zhang

2020

Biomedical Chromatography

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As a traditional Chinese medicine, Marsdenia tenacissima (Roxb.) Wight et Arn. plays an indispensable role in clinical practice owing to its specific efficacy in treating malignant tumors, leukocythemia, cystitis and asthma. This study aimed to establish a novel and scientific LC-MS/MS approach to simultaneously determine tenacissoside B, H, G and I, caffeic acid, cryptochlorogenic acid, chlorogenic acid and neochlorogenic acid from M. tenacissima extract within the rat plasma samples. Digoxin was used as the internal reference. All determinations were carried out using the Eclipse Plus C 18 column, and water (containing 0.1% formic acid) was used as the mobile phase A, while acetonitrile was the mobile phase B for gradient elution. The UPLC methods were validated, including calibration curves, accuracy, precision, stability and recovery of the total eight analytes, in accordance with the requirements for biopharmaceutical analysis. Moreover, the proposed approach was also used in comprehensive pharmacokinetic research on those eight analytes in rats following M. tenacissima extract gavage. According to the pharmacokinetic parameters, tenacissoside B, I, H and G are the long-acting and primary bioactive constituents in M. tenacissima extract, with long mean residence times and high concentrations. Our findings shed light on the absorption mechanism and provide significant information for the clinical application of M. tenacissima.

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“…However, one of our previous studies revealed that linarin shows low bioavailability (0.47%) after oral administration, which suggests that linarin could be extensively metabolized after oral administration, and the metabolites of linarin could still show various pharmacological activities [11]. Acacetin, apigenin, and p -hydroxy benzaldehyde (Figure 1) have been identified as the metabolites of linarin [12]. We found that these three metabolites showed a protective effect against severe d -GalN-induced hepatic failure in rats (data not shown).…”

Section: Introductionmentioning

confidence: 99%

LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin

et al. 2019

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Linarin, a flavone glycoside, is considered to be a promising natural product due to its diverse pharmacological activities. Recently, it has been brought into focus for its potential to treat liver failure. In this study, a rapid and sensitive liquid chromatography electrospray-ionization tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of linarin and its three metabolites (acacetin, apigenin, and p-hydroxy benzaldehyde) in plasma and liver tissue samples of normal rats and rats with d-galactosamine (d-GalN)-induced liver injury. After liquid–liquid extraction (LLE) with ethyl acetate, chromatographic separation of the four analytes was achieved using an ACQUITY UPLC BEH-C18 (1.7 μm, 2.1 × 50 mm) with a mobile phase of 0.01% formic acid in methanol and 0.01% formic acid at a flow rate of 0.3 mL/min. The detection was accomplished on a tandem mass spectrometer via an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in the negative ionization mode. The method had a good linearity over the concentration range of 1.00–200 ng/mL for linarin and its metabolites. The validated method was successfully applied to the pharmacokinetic and liver tissue distribution study of linarin and its metabolites after a single oral administration of linarin (90 mg/kg) to rats.

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Characterization of the In Vivo and In Vitro Metabolites of Linarin in Rat Biosamples and Intestinal Flora Using Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry

Cited by 29 publications

References 20 publications

A Complete Study of Farrerol Metabolites Produced In Vivo and In Vitro

A Complete Study of Farrerol Metabolites Produced In Vivo and In Vitro

Simultaneous determination of eight bioactive components in Marsdenia tenacissima extract in rat plasma by LC–MS/MS and its application in a pharmacokinetic study

LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin

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