JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2019
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IF 2.983
Bolin Zhu,Mengyao Xue,Beibei Liu,Qing Li,Xingjie Guo
In the present paper, a sensitive and selective chiral LC method has been developed for enantiomeric separation and determination of eight antihistamines in pharmaceutical formulations. Enantiomeric separation was achieved on the α 1 -acid glycoprotein-based chiral stationary phase known as Chiralpak AGP. The effects of the mobile phase composition, type and proportion of organic modifier and the concentration and pH of the buffer on retention and resolution were fully investigated. All enantiomers of target analytes were successfully separated with the mobile phase consisting of methanol and 10 mM ammonium acetate buffer, at a flow rate of 0.9 mL min −1 . Calibration curve of each enantiomer was linear over the concentration range of 5.0–100 μg mL −1 , with the correlation coefficient above 0.9990. The limits of detection and quantification were below 0.80 and 3.18 μg mL −1 , respectively. The recoveries were in the range of 98.0–102.4% with the relative standard deviation lower than 2.88% for all enantiomers. The validated method was demonstrated to be suitable for the quality control of the enantiomeric composition of antihistamines present in pharmaceuticals. Finally, the proposed chiral LC method was applied to the determination of antihistamines enantiomers in commercially available tablets containing racemic mixtures of compounds. Quantitative results of the commercial tablets demonstrated that the difference between the declared and determined values did not exceed 1.45%, and chiral antihistamines drugs were present in the form of racemates.
研究领域:
分析化学
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药物分析
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生物化学
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2024
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IF 4.3
Huan-Yu Sui,Dong Chen,Jia-Ping Huang,Zhe-Ying Hu,Lu Hu,Jie-Hua shi,Shao-Liang Jiang
Approval in 2019 was granted for the highly selective, targeted agent lorlatinib, which primary target is ROS1 and ALK. The purpose of this work was to examine the binding mechanism between lorlatinib (LOR) and HAG employing multispectral and molecular modeling techniques. Fluorescence data demonstrated that LOR quenched HAG fluorescence as a static quenching, interecalated into the hydrophobic cavity of HAG with a moderate affinity. Thermodynamic and competitive experiments pointed out that LOR bound with HAG primarily through hydrogen bonding, hydrophobic, and van der Waals forces. Circular dichroism, three-dimensional and synchronous fluorescence spectroscopic studies noted that the secondary structure of HAG and microenvironments around tyrosine (Tyr) and tryptophan (Trp) residues were altered due to binding with LOR. The contribution of each energy involved in binding process of LOR and HAG has been analyzed by molecular simulation techniques. Besides, the environmental conditions with metal ions have also been studied. The present study is expected to provide a theoretical basis for further studying the metabolism of LOR in vivo, which may help to gain a deeper understanding of the general pharmacological activity of the drug.
研究领域:
药理学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2024
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IF 4.3
Zhe-Ying Hu,Huan-Yu Sui,Qi-Feng Zhong,Lu Hu,Jie-Hua Shi,Shao-Liang Jiang,Liang Han
Dacomitinib is a highly selective second-generation tyrosine kinase inhibitor that can irreversibly bind to tyrosine kinase and is mainly used in the treatment of lung cancer. The binding characteristics of dacomitinib with human α 1-acid glycoprotein (HAG) were analyzed by multispectral and computational simulation techniques. The fluorescence spectra showed that dacomitinib can quench the fluorescence of HAG by forming the HAG-dacomitinib complex with a molar ratio of 1:1 (static quenching). At the temperature similar to that of the human body, the affinity of dacomitinib to HAG (8.95 × 10 6 M −1 ) was much greater than that to BSA (3.39 × 10 4 M −1 ), indicating that dacomitinib will give priority to binding onto HAG. Thermodynamics parameters analysis and driving force competition experiments showed that hydrogen bonding and hydrophobic forces were the major sources for keeping the complex of HAG-dacomitinib stable. The experimental outcomes also showed that the binding of dacomitinib can lead to the loosening of the skeleton structure of HAG, which led to a slight change in the secondary structure , and also reduces the hydrophobicity of the microenvironment of Trp and Tyr residues. The binding sites of dacomitinib on HAG and the contribution of key amino acid residues to the binding reaction were determined by molecular docking and molecular dynamics (MD) simulation. In addition, it was found that there was a synergistic effect between dacomitinib and Mg 2+ and Co 2+ ions. Mg 2+ and Co 2+ could increase the K b of dacomitinib to HAG and prolong the half-life of dacomitinib.
研究领域:
药理学
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生物化学
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计算生物学
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2023
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IF 4.4
Shao-Liang Jiang,Wan-Jun Wang,Zhe-Ying Hu,Rong-Juan Zhang,Jie-Hua Shi
The primary coverage of this paper is to investigate the molecular interaction of JAK2 inhibitor, fedratinib (FED) with BSA/HAG proteins through multispectral approaches and molecular docking as well as MD calculation. Arrival at a conclusion, the endogenous fluorescence of BSA/HAG protein was quenched separately in the form of static and mixed quenching. The FED-BSA and FED-HAG complexes with the stoichiometric ratio of 1:1 were formed in the interaction process. And, The K b values of these complexes were of 10 4 –10 5 M −1 and 10 5 –10 6 M −1 , respectively, representing that the FED-HAG complex exhibited a comparatively high affinity compared to the FED-BSA complex. It is confimed that FED inserted into the interface area between subdomain IIA and IIB of BSA (marked as site II') and the bucket-shaped hydrophobic cavity of HAG, respectively, resulting in the slight alteration in the secondary structure of BSA/HAG and the micro-environment round Tyr and Trp residues. The expetimental results also confirmed that van der Waals forces (VDW), hydrogen bonds and hydrophobic interaction played a dominant role in the formation of two stable complexes. The above experimental results were supplemented and verified through molecular docking and MD simulation. Meanwhile, the effects of common ions on affinity were explored. This study could shine a light on evaluating the pharmacological properties of the JAK inhibitor FED, understanding the distribution and operation of the drug in the body, and leading to the development of the creation of novel medication devise.
研究领域:
药理学
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生物化学
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计算生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2025
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IF 4
Liang Xu,Jinjian Yao,Zhen Wang,Songzi Xie,Jinmei Ou,Bin Wang
Conventional methods for analyzing monosaccharides, such as 1-Phenyl-3-methyl-5-pyrazolone (PMP) derivatization coupled with high-performance liquid chromatography (HPLC), struggle to detect ketoses and acidic sugars. This limitation hinders the precise structural analysis of polysaccharides in traditional Chinese medicine (TCM). A methylation-assisted Gas Chromatography-Mass Spectrometry (GC–MS) approach was developed to address this issue in the current study. By optimizing the methylation process and using GC–MS with a BR-17 column and an Electron Ionization (EI) source, simultaneous detection of ten different monosaccharides was achieved within 20 min. GC–MS profiling of monosaccharides generally gives two peaks per analyte, except in the cases of fructose and galacturonic acid. Notably, fructose (Fru) was identified for the first time in the polysaccharides of Polygonatum species: P. sibiricum at 18.55 μg/mg, P. cyrtonema at 16.90 μg/mg, and P. kingianum at 14.35 μg/mg, overcoming the limitations of the inability to detect ketoses in the PMP-HPLC method. Data analysis revealed distinct species-specific markers: P. kingianum polysaccharides (PKP) uniquely contained α -galacturonic acid (α-Gal: 19.95 μg/mg), whereas P. sibiricum polysaccharides (PSP) featured six monosaccharides, including glucose (Glc: 135.45 μg/mg), mannose (Man: 78.95 μg/mg), and ribose (Rib: 26.90 μg/mg), with a total of 299.50 μg/mg. P. cyrtonema polysaccharides (PCP) showed elevated levels of glucuronic acid (GlcA, 38.40 μg/mg). This derivatization-enhanced GC–MS method effectively fingerprints TCM polysaccharides, enabling clear differentiation of Polygonatum species through analysis of monosaccharide composition and total sugar content. This approach establishes clear structural distinctions, overcoming the limitations of conventional chromatographic techniques and enhancing the quality control and authentication of TCM polysaccharides.
研究领域:
分析化学
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碳水化合物化学
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植物化学
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中医药学
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质谱分析
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）