JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2017
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IF 3.255
Xiaoxue Liu,Chenrong Huang,Ling Xue,Qingqing Xu,Wen Xia,Xing Li,Liyan Miao
A rapid and highly sensitive liquid chromatography-tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the determination of a novel anti-HBV compound Y101 and its metabolites M8 and M9 in human plasma. The plasma samples were deproteinated with acetonitrile after addition of Peramivir (internal standard, IS) and separated on a 40 °C ACQUITY UPLC BEH C 18 column (2.1 mm × 50 mm, 1.7 μm). The mobile phase consisted of water (containing 5 mM ammonium acetate and 0.1% formic acid) and acetonitrile (74:26, v/v) at a flow rate of 0.3 mL/min. The detection was performed on a Triple Quad 5500 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive mode. Quantification was conducted by multiple reaction monitoring (MRM) of the transitions of m / z 490.1 → 339.0 for Y101, m / z 357.2 → 105.2 for metabolite M8, m / z 373.1 → 105.1 for metabolite M9 and m / z 329.1 → 270.2 for IS, respectively. The method was validated over the calibration curve range of 1.000–1000 ng/mL for Y101, 2.000–2000 ng/mL for metabolite M8 and 0.3000–300.0 ng/mL for metabolite M9, using linear regression and 1/x 2 weighting. No matrix effect and carryover effect was observed. The intra- and inter-batch precision and accuracy of Y101, metabolite M8 and M9 were all within the acceptable criteria. This method allows a rapid and simple determination of Y101 and its metabolites M8 and M9 in human plasma. It was successfully applied in a pharmacokinetic study in human for the first time.
研究领域:
药理学
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分析化学
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临床药理学
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DOI
PubMed
高影响因子
Arabian Journal of Chemistry
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2023
·
IF 6
Xucong Huang,Zhenghua Wu,Yanchao Liu,Mengqi Jia,Wenjuan Zhao,Shuowen Wang,Xinhui Jiang,Yuefen Lou,Guorong Fan
A simple, sensitive, and rapid LC-MS/MS method for the simultaneous determination of BIC, the M7 and M8 active metabolites in SD rat plasma was developed. After salting-out assisted liquid–liquid extraction (SALLE) with 5 M ammonium acetate solution, the sample was analyzed on a Sciences column (C18 3.0 × 100 mm, 3 μm) using a gradient elution at 40 ℃ within 7 min. The assay displayed excellent linearity in the range of 4–2000 ng/mL for M7 and BIC, and 1–500 ng/mL for M8. The results of this method exhibited that the precision, accuracy, matrix effect, recovery, and stability of BIC, M7 and M8 met all requirements for the quantitation in plasma samples. The pharmacokinetic result showed that the AUC (0→t) was calculated as 383.1 ± 164.4 (ng/mL·h) for BIC, and 5627 ± 1261 (ng/mL·h) for M7 after oral administration with BIC. Compared with BIC group, the pharmacokinetic parameters in BIC-NPs group were improved. Augmentation in AUC (0→t) (3.02-fold) and t 1/2 (1.43-fold) for BIC. Meanwhile, double peak phenomenon was observed on the mean plasma concentration–time curves of M7 in BIC and BIC-NPs group. In conclusion, both BIC and BIC-NPs were metabolized to abundant M7 in SD rat, which would provide a basis for researching the treatment mechanism of liver injury.
研究领域:
药物代谢
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药理学
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分析化学
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DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2023
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IF 13.6
Jinghua Li,Yiwen Ou,Lijuan Wang,Yue Zheng,Weiyun Xu,Jianbiao Peng,Xin Zhang,Zhiguo Cao,Junpei Ye
For the bioremediation of mixed-contamination sites, studies on polycyclic aromatic hydrocarbon (PAH) degradation or Cd (II) tolerance in bacteria are commonly implemented in nutrient-rich media. In contrast, in the field, inocula usually encounter harsh oligotrophic habitats. In this study, the environmental strain Paraburkholderia fungorum JT-M8 was used to explore the overlooked Cd (II) defense mechanism during PAH dissipation under P-limited oligotrophic condition. The results showed that the growth and PAH degradation ability of JT-M8 under Cd (II) stress were correlated with phosphate contents and exhibited self-regulating properties. Phosphates mainly affected the Cd (II) content in solution, while the cellular distribution of Cd (II) depended on Cd (II) levels; Cd (II) was mainly located in the cytoplasm when exposed to less Cd (II), and vice versa. The unique Cd (II) detoxification pathways could be classified into three aspects: (i) Cd (II) ionic equilibrium and dose–response effects regulated by environmental matrices (phosphate contents); (ii) bacterial physiological self-regulation, e.g., cell surface-binding, protein secretion and active transport systems; and (iii) specific adaptive responses (flagellum aggregation). This study emphasizes the importance of considering culture conditions when assessing the metal tolerance and provides new insight into the bacterial detoxification process of complex PAH-Cd (II) pollutants.
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PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2022
·Vol. 102
·期 10
·4054-4064
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IF 4.125
Xianxian Dong,Yin Wan,Yanru Chen,Xiaojiang Wu,Yulong Zhang,Mengfei Deng,Wenqin Cai,Xiaodan Wu,Guiming Fu
BACKGROUND Tannase is an enzyme produced by microbial fermentation and is widely used in the food industry; however, the molecular mechanism of tannase production by Aspergillus has not yet been studied. This study was conducted to reveal the differences in Aspergillus carbonarius tannase enzymatic characterization, secondary structures and molecular mechanisms after treatment of the strain with atmospheric and room temperature plasma (ARTP). RESULTS The results showed that the specific activity of tannase was improved by ARTP treatment, and it showed higher thermostability and tolerance to metal ions and additives. The enzymatic characterization and molecular docking results indicated that tannase had a higher affinity and catalytic rate with tannic acid as a substrate after ARTP treatment. In addition, the docking results indicated that Aspergillus tannases may catalyze tannic acid by forming two hydrogen-bonding networks with neighboring residues. RNA-seq analysis indicated that changes in steroid biosynthesis, glutathione metabolism, glycerolipid metabolism, oxidative phosphorylation pathway and mitogen-activated protein kinase signaling pathways might be crucial reasons for the high production of tannase. CONCLUSION ARTP enhanced the yield and properties of A. carbonarius tannase by changing the enzyme structure and cell metabolism. This study provides a theoretical basis for elucidating the molecular mechanism underlying high production of Aspergillus tannases. © 2022 Society of Chemical Industry.
研究领域:
微生物学
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生物化学
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基因组学
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酶学
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分子生物学
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PubMed
高影响因子
MOLECULES
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2023
·Vol. 28
·期 4
·1995
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IF 4.6
Aijie Zhang,Fanlong Yang,Yang Yuan,Cai Li,Xiaokui Huo,Jing Liu,Shenzhi Zhou,Wei Li,Na Zhang,Jianfeng Liu,Shiqi Dong,Huirong Fan,Ying Peng,Jiang Zheng
Bentysrepinine (Y101) is a novel phenylalanine dipeptide for the treatment of hepatitis B virus. Renal excretion played an important role in the elimination of Y101 and its metabolites, M8 and M9, in healthy Chinese subjects, although the molecular mechanisms of renal excretion and potential drug–drug interactions (DDIs) remain unclear. The present study aimed to determine the organic anion transporters (OATs) involved in the renal disposition of Y101 and to predict the potential DDI between Y101 and entecavir, the first-line agent against HBV and a substrate of OAT1/3. Pharmacokinetic studies and uptake assays using rat kidney slices, as well as hOAT1/3-HEK293 cells, were performed to evaluate potential DDI. The co-administration of probenecid (an inhibitor of OATs) significantly increased the plasma concentrations and area under the plasma concentration–time curves of M8 and M9 but not Y101, while reduced renal clearance and the cumulative urinary excretion of M8 were observed in rats. The time course of Y101 and M8 uptake via rat kidney slices was temperature-dependent. Moreover, the uptake of M8 was inhibited significantly by probenecid and benzylpenicillin, but not byp-aminohippurate or tetraethyl ammonium. M8 was found to be a substrate of hOAT3, but Y101 is not a substrate of either hOAT1 or hOAT3. Additionally, the entecavir inhibited the uptake of M8 in the hOAT3-transfected cells and rat kidney slices in vitro. Interestingly, no significant changes were observed in the pharmacokinetic parameters of Y101, M8 or entecavir, regardless of intravenous or oral co-administration of Y101 and entecavir in rats. In conclusion, M8 is a substrate of OAT3 in rats and humans. Furthermore, M8 also mediates the DDI between Y101 and entecavir in vitro, mediated by OAT3. We speculate that it would be safe to use Y101 with entecavir in clinical practice. Our results provide useful information with which to predict the DDIs between Y101 and other drugs that act as substrates of OAT3.Keywords:Y101;entecavir;renal excretion;organic anion transporters;drug-drug interaction
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
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