Simultaneous determination of active xanthone glycosides, timosaponins and alkaloids in rat plasma after oral administration of Zi-Shen Pill extract for the pharmacokinetic study by liquid chromatography–tandem mass spectrometry

Cai, Fei; Xu, Wen; Wei, Hua; Sun, Lianna; Gao, Shouhong; Yang, Qi; Feng, Jia‐Xun; Zhang, Feng; Chen, Wansheng

doi:10.1016/j.jchromb.2010.05.024

Cited by 70 publications

(41 citation statements)

References 26 publications

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“…Obvious double peaks in rat plasma were previously observed after oral administration of TB-2 (Cai et al, 2008) or herbal medicine (Cai et al, 2010). In this study, distinct double peaks were observed not only in portal vein plasma and abdominal aorta plasma but also in the liver after oral administration (Fig.…”

Section: Discussionsupporting

confidence: 74%

The Hepatobiliary Disposition of Timosaponin B2 Is Highly Dependent on Influx/Efflux Transporters but Not Metabolism

Sheng

Tian

et al. 2014

Drug Metab Dispos

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The purpose of this study was to characterize the hepatobiliary disposition of timosaponin B2 (TB-2), a natural saponin. Although TB-2 has multiple pharmacologic activities, the mechanism of its hepatobiliary disposition has not been explored. Because the metabolism of TB-2 is limited and the accumulation of TB-2 in primary hepatocytes is highly temperature dependent (93% of its accumulation is due to active uptake), the contribution of hepatic transporters was investigated. Organic anion-transporting polypeptide (OATP) 1B1-and OATP1B3-transfected human embryonic kidney 293 cells were employed. TB-2 serves as a substrate for OATP1B1 and OATP1B3, with the former playing a predominant role in the hepatic uptake of TB-2. An inhibition study in sandwich-cultured rat hepatocytes suggested that TB-2 is a substrate for both breast cancer resistance protein (Bcrp) and multidrug resistance-associated protein 2 (Mrp2), consistent with its high biliary excretion index (43.1-44.9%). This hypothesis was further verified in BCRP and MRP2 membrane vesicles. The cooperation of uptake and efflux transporters in TB-2 hepatic disposition could partially explain the doublepeak phenomenon observed in rat plasma and liver and biliary clearance, which accounted for 70% of the total TB-2 clearance. Moreover, TB-2 significantly increased the rosuvastatin concentration in rat plasma in a concentration-dependent manner and decreased its biliary excretion, which corresponded to reductions in rosuvastatin accumulation in hepatocytes and the biliary excretion index in sandwich-cultured rat hepatocytes, representing a perfect example of a potential saponin-statin drug-drug interaction. These studies demonstrate that transporters (Oatp, Bcrp/Mrp2), but not metabolism, contribute significantly to rat TB-2 hepatobiliary disposition.

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Section: Discussionsupporting

confidence: 74%

The Hepatobiliary Disposition of Timosaponin B2 Is Highly Dependent on Influx/Efflux Transporters but Not Metabolism

Sheng

Tian

et al. 2014

Drug Metab Dispos

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“…This finding is consistent with that in a previous study in which neomangiferin was absorbed promptly at a T max of 0.58 h after oral administration of the Zi-Shen Pill extract [7]. The C max of neomangiferin reached 1804.28 ng/mL, whereas the t 1/2 was only 0.95 ± 0.31 h, which is much lower than the corresponding value obtained after the oral administration of the Zi-Shen Pill [7]. The C max of mangiferin was 824.48 ng/mL, and the plasma concentration slowly declined with a relatively long elimination t 1/2 of 3.22 h. Hence, the elimination rate of mangiferin was slower than that of neomangiferin.…”

Section: Conditionsupporting

confidence: 93%

“…Mangiferin has been investigated extensively because of its remarkable pharmacological effects, including antioxidant [7,8], anti-inflammatory [9], antidiabetic [10], anticancer [11], antibacterial [12], anti-HIV [13], and radioprotective activities [14]. Notably, neomangiferin is likely biotransformed to mangiferin in vivo [7].…”

Section: Introductionmentioning

confidence: 99%

The Pharmacokinetics and Metabolism of Neomangiferin, a Major Bioactive Component in Anemarrhena asphodeloides

Gao¹,

Liu²

2016

Med chem

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“…Many modern MS instruments are now capable of fast polarity switching during data acquisition and have been exploited in simultaneous acquisition of both positive and negative ion mode data (68,69). The use of both positive and negative ionization LC-MS offers more comprehensive metabolome coverage than the use of a single polarity (50,67).…”

Section: Chromatography Coupled To Msmentioning

confidence: 99%

Mass Spectrometry Strategies in Metabolomics

Lei

Huhman

Sumner

2011

Journal of Biological Chemistry

422

351

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MS has evolved as a critical component in metabolomics, which seeks to answer biological questions through large-scale qualitative and quantitative analyses of the metabolome. MSbased metabolomics techniques offer an excellent combination of sensitivity and selectivity, and they have become an indispensable platform in biology and metabolomics. In this minireview, various MS technologies used in metabolomics are briefly discussed, and future needs are suggested.Metabolomics is idealized as the large-scale, qualitative, and quantitative study of all metabolites in a given biological system. Unlike transcripts and proteins, the molecular identity of metabolites cannot be deduced from genomic information. Thus, the identification and quantification of metabolites must rely on sophisticated instrumentation such as MS, NMR spectroscopy, and laser-induced fluorescence detection. Each of these technologies has its own unique advantages and disadvantages. Optimal selection of a particular technology depends on the goals of the study and is usually a compromise among sensitivity, selectivity, and speed.NMR is highly selective and non-destructive and is generally accepted as the gold standard in metabolite structural elucidation, but it suffers from relatively lower sensitivity. Laser-induced fluorescence is one of the most sensitive techniques, but it lacks the chemical selectivity that is critical in structural identification. In contrast, MS offers a good combination of sensitivity and selectivity. Modern MS provides highly specific chemical information that is directly related to the chemical structure such as accurate mass, isotope distribution patterns for elemental formula determination, and characteristic fragment ions for structural elucidation or identification via spectral matching to authentic compound data. Moreover, the high sensitivity of MS allows detection and measurement of picomole to femtomole levels of many primary and secondary metabolites. These unique advantages make MS an important tool in metabolomics (1, 2).Modern MS offers an array of technologies that differ in operational principles and performance. Variations include ionization technique, mass analyzer technology, resolving power, and mass accuracy. The most common ionization techniques in metabolomics include electron ionization, electrospray ionization (ESI), 2 and atmospheric pressure chemical ionization (APCI). Other ionization techniques such as chemical ionization, MALDI, and, more recently, desorption ESI (DESI) (3) and extractive ESI (EESI) (4) have also been used. Mass analyzers with different resolving powers have also been used in metabolomics. These include ultrahigh and high resolution MS such as Fourier transform ion cyclotron resonance MS (FT-ICR-MS), orbitrap MS, and multipass TOF-MS. However, lower resolution instruments such as ion traps (both linear and three-dimensional quadrupoles) and single quadrupoles are utilized by many. Each of these mass analyzers has its own advantage and limitation. Selection of a specific MS pl...

show abstract

Simultaneous determination of active xanthone glycosides, timosaponins and alkaloids in rat plasma after oral administration of Zi-Shen Pill extract for the pharmacokinetic study by liquid chromatography–tandem mass spectrometry

Cited by 70 publications

References 26 publications

The Hepatobiliary Disposition of Timosaponin B2 Is Highly Dependent on Influx/Efflux Transporters but Not Metabolism

The Hepatobiliary Disposition of Timosaponin B2 Is Highly Dependent on Influx/Efflux Transporters but Not Metabolism

The Pharmacokinetics and Metabolism of Neomangiferin, a Major Bioactive Component in Anemarrhena asphodeloides

Mass Spectrometry Strategies in Metabolomics

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