Simultaneous determination of the novel tyrosine kinase inhibitor meditinib and its active metabolite demethylation meditinib in monkey plasma by liquid chromatography–tandem mass spectrometry and its application to pharmacokinetic studies

4区 · 医学

Article

作者: Liang, Feng ; Ding, Rigao ; Cai, Jinling ; Wang, Yu ; Guan, Yongbiao ; Guo, Yongqi ; Kong, Qi ; Liu, Shi ; Sun, Dejie

AbstractMeditinib (ME) is a novel tyrosine kinase inhibitor used as an antichronic myeloid leukemia drug. A simple, sensitive and specific LC/MS/MS method was developed and validated for the analysis of ME and its metabolite demethylation meditinib (PI) in monkey plasma using naltrexone as the internal standard. Sample preparation involved protein precipitation with methanol. The analysis was carried out on an Agilent C8 column (3.5 µm, 2.1 × 50 mm). Elution was achieved with a mobile phase gradient varying the proportion of a water solution containing 0.1% formic acid (solvent A) and a 0.1% formic acid in methanol solution (solvent B) at a flow rate of 300 μL/min. The method had a linear calibration curve over the concentration range of 2–1000 ng/mL for ME and 2–1000 ng/mL for PI. The lower limits of quantification of ME and PI were 2 and 2 ng/mL, respectively. The intra‐ and inter‐day precision values were <15% and accuracy values were within ±10.0%. The mean recoveries of ME and PI from plasma were >85%. The assay has been successfully used for pharmacokinetic evaluation of ME and PI using the monkey as an animal model, and those data are reported for the first time. Copyright © 2015 John Wiley & Sons, Ltd.

2011-04-01·Journal of Applied Microbiology3区 · 生物学

Immunostimulatory activities of specific bacterial secondary metabolite ofAnoxybacillus flavithermusstrain SX-4 on carp,Cyprinus carpio

3区 · 生物学

Article

作者: Y. Lei ; F. Wang ; Y. Liu ; J. Liu ; G. Wang ; Y. Yi

AIMSTo determine the capacity of secondary metabolite of strain SX-4, to enhance the nonspecific immunity and survival of carp (Cyprinus carpio), and to identify the constituents that are responsible.METHODS AND RESULTSA thermophilic strain SX-4 that is able to produce immunostimulatory metabolite was isolated from sludge sample of hot spring and identified by comparison with 16S rRNA sequences (99% of homology) as Anoxybacillus flavithermus. Bioactivity-guided fractionation of methanol extract from its cell-free culture, one bacterial peptide with the capacity of improving the nonspecific immune responses and disease resistance (relative per cent survival = 66·67%) was obtained and the compound was characterized as cyclo-(L-Pro-Gly) by IR, ESI-MS, (1) H NMR and (13) C NMR spectroscopic analyses. After intraperitoneal administration of this peptide, selected innate immune parameters including phagocytic activity, superoxide anion production, serum lysozyme activity and serum SOD activity, along with immune-related genes expression (i.e. interleukin-1β and inducible nitric oxide synthase), in the blood were found to be significantly increased.CONCLUSIONSThe bacterial peptide cyclo-(L-Pro-Gly) significantly enhances nonspecific immunity and survival of carp.SIGNIFICANCE AND IMPACT OF THE STUDYThere is a possibility of using cyclo-(L-Pro-Gly) as a better natural immunostimulant, which could have a promising role in aquaculture to prevent diseases and disease outbreaks.

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适应症	最高研发状态	国家/地区	公司	日期
费城染色体阳性慢性粒细胞白血病	临床1期	中国	北京美迪康信医药科技有限公司	2016-09-08
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