MICROCHEMICAL JOURNAL
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2021
·
IF 4.821
Fábio de Souza Barbosa,Leonardo Capra Pezzi,Fávero Reisdorfer Paula,Sarah Eller,Elfrides E.S. Schapoval,Tiago Franco de Oliveira,Andreas S.L. Mendez
In the present study, the stability of the antibiotic doripenem was evaluated with a focus on identifying the degradation products generated. For this, a method by LC-ESI-Q-TOF was developed and validated. Also, as an auxiliary tool in the identification of degradation products, Zeneth 7 software was used in the prediction of drug degradation in silico . Under stress conditions six degradation products were detected and based on the literature and MS 2 analyzes, their structures were proposed. Under hydrolytic conditions, in acid, neutral and alkaline media, the major degradation product was formed through the cleavage of the β -lactam ring. In neutral hydrolysis, the formation of two drug dimers was also observed. Oxidation of the drug using H 2 O 2 (3%) led to the formation of three degradation products, not yet reported in the literature, generated by oxidation of the thioether group and by decarboxylation reaction. The most probable elemental compositions for degradations products were obtained with a high degree of confidence, where the error between the masses observed and calculated was less than 5 ppm. The stability of doripenem after reconstitution was studied in conditions that simulate its clinical use. At room temperature, the drug demonstrated a similar degradation profile when prepared using 0.9% NaCl and 5% glucose for infusion, keeping its content > 90% for at least 8 h, and the LC-ESI-Q-TOF analyzes detected the formation of three degradation products, highlighting two different dimers. Finally, all the data generated helps to understand the degradation behavior of doripenem and its important antibiotic class.
研究领域:
药物化学
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分析化学
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药物稳定性
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Rifa Qiao,Lifen Zhou,Minyong Zhong,Min Zhang,Lin Yang,Yuanfeng Yang,Haifang Chen,Wuliang Yang,Jinbin Yuan
Ethnopharmacological relevance Nowadays, gastrointestinal motility disorders (GMD) have reduced the quality of people's daily life worldwide, but there is still a lack of effective western medicine treatment. Fructus aurantii (FA), a representative regulating-qi herbal medicine, has been widely used to treat GMD in China for thousands of years, but it is not clear that which specific components contribute to the efficacy. Aim of the study The efficacy differences of various fractions of FA on normal mice and GMD rats were compared, so as to find out the main effective fraction of FA, and to screen the main regulating-qi components based on spectrum-effect relationship and multivariate statistical analysis. Materials and methods The fingerprints of different fractions of FA were established and main compounds were identified with UHPLC-Q-TOF/MS technique. The promoting gastrointestinal motility activities of FA were evaluated by defecation test, gastric emptying and intestinal propulsion test in mice, and further investigated according to the biochemical analysis of 5-HT, SP , MLT, GAS and VIP in GMD rats’ plasma. One-way ANOVA was used to find out the difference of efficacy. The active components were screened through spectrum-effect relationship with PCA-X, Pearson bivariate correlation analysis and OPLS analysis. Conclusions Ethyl acetate fraction is the main active fraction, and nine compounds are the major regulating-qi components. The developed spectrum-effect analysis can be used for the screening of bioactive components in natural products with high accuracy and reliability.
研究领域:
药理学
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民族药理学
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分析化学
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中药学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2018
·Vol. 410
·期 18
·4311-4322
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IF 3.307
Wu Si-Qi,Song Hui-Peng,Li Bin,Liu Run-Zhou,Yang Hua,He Ling,Li Ping
Development of fast and accurate methods to discover lead compounds for drug candidates is highly important. In this study, a reliable and effective post-column on-flow biochemical assay (POBA) was established to screen potent peroxidase inhibitors from complex chemical mixtures (e.g., natural product extracts). Multiple factors such as flow rate, organic phase, detection wavelength, and reaction coil were carefully investigated. To better understand the features of POBA, another emerging technology of ultrafiltration LC-MS was used for comparison. The result showed that POBA had advantages in saving time, avoiding false positives, and improving the accuracy. To illustrate the practicality of the method, Radix Salvia Miltiorrhizae, a traditional herb for cardiovascular disease treatment, was applied as the research objective. Finally, six compounds including tanshinol, protocatechuic aldehyde, salvianolic acid D, rosmarinic acid, lithospermic acid, and salvianolic acid B were determined as novel peroxidase inhibitors. Their bioactivities were validated by microplate-based assay, molecular docking, and pharmacophore modeling. This study demonstrates a great potential of POBA in the efficient and accurate discovery of drug candidates.
Compared with a classical method of ultrafiltration LC-MS, the newly developed method of on-flow bioassay shows advantages in saving time, avoiding false positives and improving the accuracy
研究领域:
药理学
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分析化学
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天然产物研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2023
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IF 3
Yue-Hua Chen,Si-Yu Li,Dan Wang,Wei Yuan,Kun Xu,Jia-Wei Wang,Ting-Guo Kang,Hui Zhang
Marsdenia tenacissima is a traditional Chinese medicinal plant used for treating cancer, and its main medicinal part is the stem. Considering the resource shortage of M. tenacissima , it is of great significance to improve its utilization efficiency. Steroids and caffeoylquinic acids, the two main components of M. tenacissima , are composed of several basic structures. Based on this rule, a novel strategy of combinatorics-based chemical characterization was proposed to analyze the constituents of roots, stems and leaves of M. tenacissima . Combinatorics was used to generate a compound library for structure alignment, which has the advantages of wide coverage and high specificity. Steroids are composed of four basic parts: core skeleton (C), substituent at position 11 (A), substituent at position 12 (B) and sugar moiety (S). Based on combinatorics, a compound library consisting of 1080 steroids was generated. Diagnostic neutral loss has been used to effectively predict the substituents at position 11 and 12 of steroids, including acetyl, 2-methylpropionyl, tigloyl, 2-methylbutyryl and benzoyl. As a result, 131, 131 and 99 components were detected from the roots, stems and leaves of M. tenacissima , respectively. Principal component analysis (PCA) was used to analyze the differences of roots, stems and leaves, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was further applied to find differential components. Tenacissoside H, a critical indicator component for quality evaluation of the stem, has been proved to be a differential component between roots and stems. Notably, the relative content of tenacissoside H in the roots was significantly higher than that in the stems. The bioactivity comparison showed that roots, stems and leaves of M. tenacissima had similar scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. However, their α-glucosidase inhibitory activity was ranked as leaves > stems > roots. Therefore, besides stems, the other parts of M. tenacissima have potential medicinal value. This study not only helps to develop the resource of M. tenacissima , but also provides a paradigm for the research of other similar medicinal plants.
研究领域:
药用植物学
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分析化学
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中药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2023
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IF 3
Jing Zhang,Wenyuan Li,Luming Xie,Changfeng Zhong,Changmei Wang,Lin Chen,Yifan Feng,Xia Wu
To provide the basis for further development and research of drugs, non-clinical pharmacokinetics studies were conducted on HM475, which is composed of natural active molecules honokiol and metformin through cyclization. In this paper, HM475 was studied from six aspects by gavage and intraperitoneal injection: 1) Acute toxicity of HM475 in rats, 2) Pharmacokinetic characteristics of HM475 in rats, 3) Distribution characteristics of HM475 in heart, liver, spleen, lung, and kidney, small intestine, fat and brain of rats, 4) Main metabolic pathways of HM475 in rats, 5) Excretion of HM475 in rats, 6) Determination of protein binding rate of HM475 in bovine plasma, rabbit plasma, and rat plasma. Acute toxicity of HM475 on SD rats was evaluated by maximum dose method. The metabolic analysis method of HM475 in rats was first established by UPLC-Q-TOF-MS/MS technology, and the pharmacokinetic characteristics of oral administration and intraperitoneal injection were studied. Experimental results showed that HM475 had no obvious acute toxicity. The absolute oral bioavailability of HM475 was 38.45 %, and the drug concentration in plasma was higher than that in tissues. Combined with the process characteristics of HM475 in vivo , it is inferred that HM475 has enterohepatic circulation. In this study, non-clinical pharmacokinetics were systematically studied to provide data support for the clinical pharmacokinetics and pharmacodynamics of HM475, to more accurately predict the pharmacokinetic behavior of HM475 in human body and provide scientific data for the compound to enter clinical research.
研究领域:
药理学
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毒理学
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分析化学
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药物开发
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产品关联
DOI
PubMed
高影响因子
World Journal of Traditional Chinese Medicine
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2018
·Vol. 4
·期 1
·21
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IF 0
Chen Sha,Ma Hong-Yu,Deng Zhe,Zhang Jun,Cheng Jin-Tang,Chen Chang,Liu An
Objective: Anthraquinone (AQ), a major bioactive component of the traditional Chinese medicine HeShouWu, has widespread applications in industry and medicine. The objective of the current study is to explore the differences in the bioavailability of anthraquinones in vivo and the metabolism in liver microsomes. Materials and Methods: In vivo , we used a reliable UPLC-ESI-QqQ-MS/MS method to measure seven AQ compounds in the jugular vein plasma of rats following oral administration of HeShouWu. Furthermore, in order to quantify the bioavailability of AQs in vivo and to further understand the metabolism of these compounds, we compared the in vitro metabolism of AQ in different species with respect to metabolic profiles, the enzymes involved, and catalytic efficiency using liver microsomes from human (HLM), mouse (MLM), rat (RLM), and beagle dog (DLM). Results: We identified two metabolic pathways, including the hydroxylation and glucuronidation of AQ, in the liver microsomes of humans and other species using UPLC-ESI-Q-TOF. We found that substitutions on the AQ ring were crucial to the activity and regioselectivity of its hydroxylation. In general, hydroxylation activity decreased greatly with β-COOH (rhein) and enhanced dramatically with β-OH (emodin). We also found that glucuronidation of the compound emodin-8-O-β-D-glucoside acts as the main isoform in AQ hydroxylation in HLM and DLM. Total microsomal intrinsic clearance values for AQ were greatest in mouse microsomes, followed by those in dog, human, and rat microsomes. Conclusion: The absorption of different anthrquinone compounds varied based on the compound structure, the metabolism types and products of anthraquinones in liver microsomes were different in different species. These findings provide vital information for a deeper unuunderstanding of the metabolism of AQs.
研究领域:
药物代谢
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中药药理学
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分子药理学
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生物分析化学
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转化医学
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DOI
FITOTERAPIA
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2022
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IF 3.204
Jili Zou,Siran Wu,Bi Sheng,Jing An,Junhua Meng,Wang Xiong,Jiahan Tao,Wang Han,Lin Zhao,Hanlin Xu,Yonggang Chen
Objective: To investigate changes in the chemical composition of malts under different germination cycles and prepared with different processing methods, thus providing a reference for the clinical application of malt in disease treatment. Methods: Nine malt samples were analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), and the MS fragmentation pathway of 4 compounds (including hordenine , gramine , N -methyltyramine and catechin) were also analyzed. Results: By database comparison and literature search, we detected 31 compounds in raw barley and 33 compounds in both raw malt and roasted malt. Nonetheless, the most of these 33 compounds were detected higher contents in raw malt than in roasted malt. Besides, we detected 15 compounds in brown malt. At Day1 of germination, 31 compounds were detected in malt, without two alkaloids (representative: hordenine). At Day2–5, 33 compounds were detected, with different contents as shown by the peak area comparison; hordenine had a gradually increasing abundance; and nearly one third of the chemical components in barley increased gradually, one third decreased gradually, and one third tended to be stable. Conclusion: Malts under different germination cycles and prepared with different processing methods have varying active ingredients, and especially brown malt exhibits a serious loss of compounds. The tight association between the chemical composition and clinical application of malt offers a basis to the clinically scientific and reasonable selection of Chinese medicinal materials for treatment purposes.
研究领域:
药理学
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分析化学
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食品科学
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中药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
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2021
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IF 4.556
Ruixuan Zhao,Hui Zou,Renjie Zhao,Ningyang Li,Zhenjia Zheng,Xuguang Qiao
The formation of pigment precursors was investigated systematically using green models containing arginine, lysine, alanine, glycine, serine, tyrosine, glutamic acid, and aspartic acid, respectively. Pigment precursor and blue pigments during garlic greening were investigated using ultra-performance liquid chromatography and tandem high-resolution mass spectrometry with a quadrupole time-of-flight analyser (UPLC–ESI-Q-TOF-MS). The intermediate products during the formation of a pigment precursor with a 3-oxopropenyl side chain were tentatively identified. N -substituted 3,4-dimethylpyrrole pigment precursors were found to react with 2-propenesulfenic acid first, and the propenesulfenic acid side-chain decomposed to a 3-oxopropenyl side chain, which provided a hypothesis of the formation pathway. Density functional theory calculations combined with the experimental results led to the conclusion that the primary amino group located on the α-carbon reacted with 3,4-dimethylbutanedithial S -oxide to form pigment precursors. In contrast, the amino group in the amino acid R group did not participate in pigment precursors formation. The R -groups of amino acids containing hydroxyls or carboxyl groups have influential roles in the stability of N -substituted 3,4-dimethylpyrrole pigment precursors. In contrast to a previous report, larger R-groups made a more outstanding contribution to the production of blue pigments.
研究领域:
食品科学
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化学
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光谱学
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生物化学
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产品关联
DOI
高影响因子
PLANTA MEDICA
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2022
·Vol. 88
·期 14
·1369-1383
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IF 3.007
Song Mengmeng,Xu Zhuicheng,Han Sixuan,Sheng Xianjie,Chen Yan,Li Xinru,Su Yan,Li Qin,Shan Chenxiao,Xie Tong,Kang An
Agrimonia pilosa is a perennial herbaceous flowering plant, commonly known as agrimony or hairy agrimony. The dried aerial parts of this species have been widely used for the treatment of acute diarrhea, hemostasis, and other inflammation-related diseases. However, information on the in vivo metabolism of A. pilosa constituents is limited. In this study, the phytochemical profile of A. pilosa was investigated using HPLC-Q-TOF-MS/MS combined with a nontargeted diagnostic ion network analysis strategy. An information-dependent acquisition method with multiple filters was utilized to screen possible prototypes and metabolites in complex biological matrices. Furthermore, various data-processing techniques were applied to analyze possible prototypes and their metabolites in rat plasma, feces, and urine following oral administration of A. pilosa extract. A total of 62 compounds, which belonged to five main structural classes (21 phenols, 22 flavonoids, 6 coumarins, 3 triterpenes, and 10 organic acids), were tentatively identified in A. pilosa. In addition, using our proposed stepwise method, 32 prototypes and 69 metabolites were detected in rat plasma, feces, and urine. The main metabolic pathways after the oral administration of A. pilosa extract were revealed to include methylation, dihydroxylation, demethylation, hydrolysis, sulfation, and glucuronidation. This comprehensive in vivo and in vitro identification of the possible active components in A. pilosa could provide a basis for understanding its various pharmacological activities.
研究领域:
药理学
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分析化学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2024
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IF 7
Haojie Sha,Yanrong Ma,Jiaxing Li,Junying Zhao,Yunbi Xu,Dingding Su
Rice has a long history as a staple food consumed by half of the world’s population. Compared with white rice (WR), colored rice (CR) has more nutritional value because it contains rich active ingredients. In this study, the potential mechanism of CR (red rice (RR), green rice (GR), black rice (BR), and purple rice (PR)) for immunomodulation was explored by UPLC-Q-TOF, network pharmacology, and cell experiment. kuromanin, kaempferol-3-O-arabinoside, keracyanin, guajavarin, and hispidulin in CR were the critical components for improving immunity. These ingredients are mainly found in BR. Cell experiments supported that kuromanin plays a role in maintaining immune homeostasis. In the normal environment, it promotes cell proliferation and improves DNA repair; In an inflammatory environment, it binds to AKT1 and reduces the release of inflammatory factors through the MAPK and NFKB signaling pathways. The study provides a guideline for humans to utilize the precise nutrition of CR.
研究领域:
食品科学
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药理学
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免疫学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2025
·
IF 4
Xijia Zhang,Yingjie Zhuo,Qianqian Xu,Ningning Wang,Hao Zhong,Dongsheng Li,Juanjuan Zhao
Steroid hormones play a crucial role in human physiological functions, and the simultaneous quantification of multiple steroid hormones in biological matrices has considerable clinical relevance. However, the simultaneous quantification of steroid hormones in biological matrices remains analytically challenging due to their ultra-trace concentrations and substantial matrix interference. A novel complementary multi-aptamer strategy was proposed in our study. Multi-aptamer magnetic beads (MA-MBs) were synthesized by simultaneously immobilizing estrogen-specific aptamer (AptE) and corticoid-specific aptamer (AptC) on the magnetic beads. Then MA-MBs was used to extract multiple steroid hormones in biological matrices based on the combined specificity of complementary aptamers. Following extraction, the enriched steroid hormones are quantified using quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LC-MS). MA-MBs demonstrated a rapid magnetic response (5 seconds), high extraction efficiency, and excellent reusability (at least 10 cycles). Under optimal extraction conditions, the proposed MA-MBs-Q-TOF LC-MS method exhibited a wide linear range (0.02-200 ng/mL), low limits of detection (0.02-1 ng/mL), and high recovery rates (92.93%-104.93%) for 10 types of steroid hormones. Finally, the validated method was applied to quantify ten clinically-relevant steroid hormones in serum samples, demonstrating its potential for advanced endocrine research applications. Furthermore, this study provides a robust platform for multiplexed targets analysis in complex biological matrices.
研究领域:
分析化学
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内分泌学
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生物分析化学
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质谱分析
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分子识别
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产品关联
DOI
PubMed
高影响因子
Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2017
·
IF 1.059
Juan Wu,Xiao’ai Fang,Yan Yuan,Yanfen Dong,Yanling Liang,Qingchun Xie,Junfeng Ban,Yanzhong Chen,Zhufen Lv
Canarium pimela K.D. Koenig, Burseraceae, have a long history of use in the Chinese traditional medicine treatment of various ailments including hypertension, and our research team has reported the anti-hypertensive activity and delineated the mechanism involved in the action. The following research aims to evaluate the vasorelaxant and antioxidant activities of ethanol extract from C. pimela leaves and to analyze its chemical composition by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) that may correlate with their pharmacological activities. The results showed that pre-incubation of aortic rings with the extract (0.3, 1, 3, 10, 30 and 100 mg/l) significantly inhibited the contractile response of the rings to norepinephrine-induced contraction ( p < 0.01or p < 0.05). Crude ethanol extract and refined ethanol extract showed a highest inhibitory effect against 2,2dipheyl-2-picrylhydrazyl hydrate scavenging activity (IC 50 of crude ethanol extract = 15.42 ± 0.14 μg/ml and IC 50 of refined ethanol extract = 5.72 ± 0.31 μg/ml) and 2,2′-azinobis (3-ethyl-benzothiazoline-6-sulphonic acid ammonium salt) (ABTS (IC 50 of crude ethanol extract = 3.24 ± 0.18 μg/ml and IC 50 of refined ethanol extract = 1.88 ± 0.07 μg/ml) scavenging activity, which was considerably higher than that reported for butylated hydroxytoluene and lower of that measured for ascorbic acid. Moreover, its chemical composition was analyzed by UPLC/Q-TOF-MS. Sixteen compounds including nine flavonoids, four tannins, two phenolic acids and one dianthrone were identified for the first time as constituents of this species. And of this, six major phenolic components were simultaneous quantitative analysis by HPLC-UV, chlorogenic acid is the major compounds in C. pimela leaves. These results indicate that the phenolic-rich extract of C. pimela leaves is a promising natural pharmaceutical for combating hypertension and oxidative stress.
研究领域:
药理学
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分析化学
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传统中药
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）