Determination of chamaechromone in rat plasma by liquid chromatography–tandem mass spectrometry: Application to pharmacokinetic study

Lou, Yan; Liu, Yao; Yu, Qinqin; Li, Li; Li, Ping; Yu, Lushan; Jiang, Huidi; Zeng, Su

doi:10.1016/j.jpba.2011.04.009

Cited by 15 publications

(10 citation statements)

References 14 publications

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“…In a previous study, only chamaechromone has been investigated in an in vivo analysis method (Lou et al, 2011), but its plasma concentration of LLOD was not low enough, and did not satisfy the requirements of our study. In the literature, a double-peak phenomenon has been found in the plasma concentration-time curve after oral administration of purified chamechromone, which was probably caused by enterohepatic circulation.…”

Section: Pharmacokinetic Studymentioning

confidence: 81%

A UPLC‐MS/MS method for simultaneous determination of five flavonoids from Stellera chamaejasme L. in rat plasma and its application to a pharmacokinetic study

et al. 2018

Biomedical Chromatography

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Stellera chamaejasme L. has been used as a traditional Chinese medicine for the treatment of scabies, tinea, stubborn skin ulcers, chronic tracheitis, cancer and tuberculosis. A sensitive and selective ultra-high liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of five flavonoids (stelleranol, chamaechromone, neochamaejasmin A, chamaejasmine and isochamaejasmin) of S. chamaejasme L. in rat plasma. Chromatographic separation was accomplished on an Agilent Poroshell 120 EC-C column (2.1 × 100 mm, 2.7 μm) with gradient elution at a flow rate of 0.4 mL/min and the total analysis time was 7 min. The analytes were detected using multiple reaction monitoring in positive ionization mode. The samples were prepared by liquid-liquid extraction with ethyl acetate. The UPLC-MS/MS method was validated for specificity, linearity, sensitivity, accuracy and precision, recovery, matrix effect and stability. The validated method exhibited good linearity (r ≥ 0.9956), and the lower limits of quantification ranged from 0.51 to 0.64 ng/mL for five flavonoids. The intra- and inter-day precision were both <10.2%, and the accuracy ranged from -11.79 to 9.21%. This method was successfully applied to a pharmacokinetic study of five flavonoids in rats after oral administration of ethyl acetate extract of S. chamaejasme L.

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Section: Pharmacokinetic Studymentioning

confidence: 81%

A UPLC‐MS/MS method for simultaneous determination of five flavonoids from Stellera chamaejasme L. in rat plasma and its application to a pharmacokinetic study

et al. 2018

Biomedical Chromatography

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“…Sample preparation is a critical step for accurate and reliable LC − MS/MS assays. Protein precipitation (PPT) is often used for the preparation of biological samples with the advantages of simplicity and time saving (Yang et al ., ); however, PPT may cause a high noise level and interference by endogenous substances (Lou et al ., ). Liquid − liquid extraction (LLE) can produce purified as well as concentrated samples and improve the sensitivity and robustness of the assay (Chen et al ., ).…”

Section: Resultsmentioning

confidence: 97%

Comparative pharmacokinetics study of a kaurane diterpenoid after oral administration of monomer and Siegesbeckiae pubescens Makino extract to rats

Lei

Jiang

Liu

et al. 2013

Biomedical Chromatography

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In this paper, a sensitive, rapid and reproducible high-performance liquid chromatography-tandem mass spectrometry method was developed to analyze 16α-hydro-ent-kauran-17,19-dioic acid in rat plasma. First, this study compared the pharmacokinetics of 16α-hydro-ent-kauran-17,19-dioic acid after oral administration of monomer and Siegesbeckiae pubescens Makino extract in rat plasma with approximately the same dosage of 6.0 mg/kg. Second, chromatographic separation was performed on a Waters Symmetry C18 column (2.1 × 100 mm, 3.5 µm) with isocratic elution using methanol-water containing 5 mmol/L ammonium acetate (70:30, v/v) as mobile phase at a flow rate of 0.2 mL/min. The calibration curves were linear over the range of 30-12000 ng/mL for monomer. At different time points (0, 0.083, 0.25, 0.75, 1, 2, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 h) after administration, the concentrations of monomer in rat plasma were determined and main pharmacokinetic parameters were estimated. The double absorption presented in this study indicates that the pharmacokinetics of monomer in rat plasma have significant differences between different groups.

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“…Few studies have reported the metabolic characteristics of chamaechromone in human liver microsomes (HLMs). We estimated the oral bioavailability of chamaechromone in rats to be 8.9 % in our previous study [12]. Our follow-up study further established the metabolites of chamaechromone in the rat and in the rat liver S9 fraction [13].…”

Section: Intmentioning

confidence: 64%

“…Such findings have supported the belief that HLMs might be a better model to predict the metabolism of chamaechromone, in vivo, in humans. An LC-MS method [12] was used to study the enzyme kinetics of chamaechromone in HLMs and related recombinant isozymes. It was found that the enzyme kinetics for both hydroxylation and glucuronidation fit well with the Michaelis-Menten equation in HLMs.…”

Section: Intmentioning

confidence: 99%

Metabolism of Chamaechromone In Vitro with Human Liver Microsomes and Recombinant Human Drug-Metabolizing Enzymes

et al. 2014

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Chamaechromone is a major component in the dried roots of Stellera chamaejasme with antihepatitis B virus and insecticidal activity. In this study, metabolic profiles of chamaechromone were investigated in human liver microsomes. One monohydroxide and two monoglucuronides of chamaechromone were identified. The enzyme kinetics for both hydroxylation and glucuronidation were fitted to the Michaelis-Menten equation. The hydroxylation of chamaechromone was inhibited by α-naphthoflavone, and predominantly catalyzed by recombinant human cytochrome P450 1A2, whereas the glucuronidation was inhibited by quercetin, 1-naphthol, and fluconazole, and mainly catalyzed by recombinant human UDP-glucuronosyltransferase 1A3, 1A7, 1A9, and 2B7. Key wordsStellera chamaejasme · Thymelaeaceae · chamaechromone · metabolite · in vitro · human liver microsomes · recombinant human enzymes Abbreviations ! CL int : intrinsic clearance DDI: drug-drug interaction hCYP: human cytochrome P450 HLMs: human liver microsomes hUGT: human UDP-glucuronosyltransferase K m : Michaelis constant UDPGA: UDP-glucuronic acid UPLC Q-TOF MS: ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry V max : maximal velocity of formation Supporting information available online at http://www.thieme-connect.de/ejournals/toc/plantamedica Stellera chamaejasme L. (Thymelaeaceae) is a toxic perennial herb. Its root is known as Langdu and is described in the Chinese Pharmacopoeia [1] as having antiviral [2, 3], antitumor [4], antibacterial [5], immunomodulatory [6], and insecticidal effects [7, 8]. The use of Langdu along with various clinically prescribed drugs may result in a herb-drug interaction or Langdu toxicity [9]. Chamaechromone, a biflavone, is one of the major active constituents of the dried roots of S. chamaejasme [10]. The range of chamaechromoneʼs biological effects, such as its anti-HBV effect and insecticidal activity [2, 7], may explain the widespread use of Langdu. The pathways of biflavone metabolism are relatively limited compared to monomeric flavones [11]. Few studies have reported the metabolic characteristics of chamaechromone in human liver microsomes (HLMs). We estimated the oral bioavailability of chamaechromone in rats to be 8.9 % in our previous study [12]. Our follow-up study further established the metabolites of chamaechromone in the rat and in the rat liver S9 fraction [13]. However, humans and animals may display markedly different metabolic profiles with regard to the composition of different isoforms, and the expression and catalytic activities of drug-metabolizing enzymes [14]. Furthermore, HLMs and recombinant enzymes are useful in vitro tools for the prediction of drug-metabolism pathways in vivo in humans and for the identification of specific enzymes involved in these pathways. They also offer valuable insights into potential clinical drug-drug interactions [15]. They may also potentially reduce the use of animals and provide an easy drug-metabolizing enzyme assay protocol. In view of these advantages...

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Determination of chamaechromone in rat plasma by liquid chromatography–tandem mass spectrometry: Application to pharmacokinetic study

Cited by 15 publications

References 14 publications

A UPLC‐MS/MS method for simultaneous determination of five flavonoids from Stellera chamaejasme L. in rat plasma and its application to a pharmacokinetic study

A UPLC‐MS/MS method for simultaneous determination of five flavonoids from Stellera chamaejasme L. in rat plasma and its application to a pharmacokinetic study

Comparative pharmacokinetics study of a kaurane diterpenoid after oral administration of monomer and Siegesbeckiae pubescens Makino extract to rats

Metabolism of Chamaechromone In Vitro with Human Liver Microsomes and Recombinant Human Drug-Metabolizing Enzymes

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