TALANTA
·
2024
·
IF 5.6
Weiwei Chen,Kailong Yuan,Quan He,Qing Li,Jing Luo,Fengjian Chu,Huiwen Wang,Hongru Feng,Yuanjiang Pan
Mass spectrometric analysis of non-volatile salts containing samples remains challenging due to salt-induced ion suppression and contamination. This challenge is even more pronounced for a liquid chromatography-mass spectrometry analysis, where the accumulation of salts in the transmission system poses an ongoing problem. In this study, a novel thermal assisted recrystallization ionization mass spectrometry (TARI-MS) device was developed to achieve efficient on-line desalting and prolonged analysis of saline samples. The core component of this device was a heated plate positioned between the electrospray unit and the MS inlet. The desalting mechanism was demonstrated as the spontaneous separation of target molecules from salts during the “crystallization” process. After optimization, the angle between the nebulizer and the heated plate was 45°; the distance between the front end of the heated plate and the MS inlet was 2 mm; the distance between the front edge of the heated plate and the center of the sample spray projected onto the heating plate was 3 mm; the distance between the emitter of nebulizer and the heated plate was 3 mm. TARI-MS realized direct analysis of eight drugs dissolved in eight commonly used non-volatile salts solutions (up to 0.5 mol/L). The high sensitivity, repeatability, linearity, accuracy, and intra- and inter-day precision of TARI-MS confirm its reliability as a robust tool for the analysis of saline samples. Furthermore, TARI-MS allowed continuous analysis of salty eluates of LC for up to nearly 1 h without maintenance and verified the feasibility of LC-MS analysis through detecting a five-drug mixture and a crude aripiprazole product. Finally, six impurities in the crude aripiprazole product were successfully detected by LC-TARI-MS. The established method holds promise for applications across academic and pharmaceutical domains.
研究领域:
分析化学
·
药学
·
质谱
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Jin-Han Yang,Tong-Chen Bai,Lu-Li Shi,Bo Hou,Ran Tang,Rong-Ping Zhang,Xing-Long Chen
Ethnopharmacological relevance The buds of Vaccinium dunalianum Wight are used as folk medicine in the Yi settlement of the Yunnan Province, China. It has long been used as herbal tea in the local area owing to its effects of lowering blood lipids and body weight. However, there are only a few studies on its antihyperlipidemic effects, effective substances and mechanisms, especially its effectiveness in diet-induced hyperlipidemia . Aim of the study This study aimed to elucidate the therapeutic effects, pharmacodynamic material bases, and mechanisms of V. dunalianum buds on diet-induced hyperlipidemia. Materials and methods A high-fat diet-induced hyperlipidemic Sprague-Dawley (SD) rat model was established. Rats were gavaged with different doses of aqueous extract of V. dunalianum (VDW) for 8 weeks and their sera and organ samples were collected. The antihyperlipidemic effect of VDW on SD rats was evaluated based on the biochemical indices and histopathological outcomes. Liquid chromatography–mass spectrometry(LC-MS) was used to determine the main components in VDW, which were separated and purified using sequential chromatographic methods. Their chemical structures were determined using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. 6′- O -caffeoyl-arbutin, as the principal component of VDW, was also evaluated for its antihyperlipidemic activity using an approach similar to that used for VDW. Lastly, the potential targets of VDW and 6′- O -caffeoyl-arbutin in lowering blood lipids were screened out using network pharmacology , and the selected targets were docked with arbutin derivatives. The expression of target proteins was determined using western blotting to illustrate the antihyperlipidemic mechanisms of VDW and 6′- O -caffeoyl-arbutin. Results VDW reduced triglyceride , total cholesterol, low-density lipoprotein, alanine transaminase , and aspartate transaminase levels in the serum of modeled rats, and increased high-density lipoprotein levels. There was an improvement in steatoses, and lipid droplet accumulation decreased in vivo after VDW intervention. LC-MS revealed that VDW mainly contained arbutin and chlorogenic acid derivatives. Sixteen compounds were isolated and identified. 6′- O -caffeoyl-arbutin was the main compound of VDW (>21.67%) that showed obvious antihyperlipidemic effect with low hepatic damage at different doses. PTGS2, ADH1C , and MAOB were screened out using network pharmacology and they showed strong correlations with arbutin derivative through molecular docking. Results from WB showed that VDW and 6′- O -caffeoyl-arbutin could reduce blood lipid levels by reducing the protein expression of PTGS2, ADH1C, and MAOB. Conclusions 6′- O -caffeoyl-arbutin was the main component of V. dunalianum buds. VDW and 6′- O -caffeoyl-arbutin could regulate blood lipid levels in the high-fat diet-induced rat model of hyperlipidemia without damaging their vital organs. Furthermore, they could regulate the expression of PTGS2, ADH1C, and MAOB proteins and play a role in lowering blood lipids. The findings of this study lay a foundation for the further development of V. dunalianum and 6′- O -caffeoyl-arbutin as health supplements or drugs for the management of hyperlipidemia.
研究领域:
药理学
·
民族药理学
·
生物化学
·
分子生物学
·
网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Huijie Lv,Siqi Luo,Ruochen Tian,Wenhua Zhang,Baoshan Sun,Yan Cui
Epinephrine and norepinephrine are a class of chiral endogenous catecholamines, which are known as major neurotransmitters. This work described a new LC–MS/MS method coupled with pre-column derivatization, enabling the simultaneous enantiomeric separation of epinephrine and norepinephrine in rat plasma. After protein precipitation procedure, the samples were derivatized with ( S )-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester, [( S )-NIFE]. The derivatives resolved with good baseline separation on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with mobile phase composed of methanol with 0.2% formic acid in water at a flow rate of 0.2 mL/min. Analysis was performed by multiple reaction monitoring in positive ionization mode. The linear ranges were 1.0–500 ng/mL for epinephrine enantiomers and 1.5–750 ng/mL for norepinephrine enantiomers. The lower limits of quantification for epinephrine and norepinephrine enantiomers were 1.0 and 1.5 ng/mL, respectively. The intra-day and inter-day precision were all less than 10.7% and accuracy ranged from 96.0 to 101.5%. Recoveries for all the analytes were more than 80.3%. The proposed method was successfully applied to simultaneously determine endogenous epinephrine and norepinephrine enantiomers in rat plasma. l -epinephrine and l -norepinephrine were sensitively and accurately quantified while both the d -enantiomers were not detected. Additionally, epinephrine enantiomers were analyzed for stereoselective pharmacokinetics in rats after intravenous administration of racemic epinephrine for the first time. The pharmacokinetic results indicated that the disposition of epinephrine enantiomers was stereoselective and chiral inversion did not occur in rats.
研究领域:
分析化学
·
药物代谢
·
神经生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2020
·
IF 7.489
Huijing Ma,Bing Yu,Qingping Wang,Gary Owens,Zuliang Chen
While Fe-based metal-organic frameworks (MOFs) can be used to remove antibiotics by adsorption, knowledge of how antibiotics are degraded by MOFs is still limited. In this study, one Fe-based MOF, NH 2 -MIL-88B was used to remove pefloxacin from aqueous solution via a combination of adsorption and Fenton-like oxidation. NH 2 -MIL-88B exhibited a high adsorption capacity for pefloxacin (41.37 mg·g −1 ), with >99% removal efficiency within 120 min based on Fenton-like oxidation. To better understand the mechanisms involved in integrated adsorption and Fenton-like oxidation, various advanced characterization techniques were used to monitor the changes in morphology and composition of NH 2- MIL-88B before and after removal of pefloxacin. Scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) all supported adsorption and Fenton oxidation of pefloxacin. In addition, the pefloxacin degradation products identified by LC-UV and LC-MS provided information on the potential adsorption-Fenton oxidation mechanism. These results suggested that NH 2 -MIL-88B has remarkably potential to be used in an integrated adsorption and Fenton-like process for the removal of antibiotics from aqueous solution.
研究领域:
环境科学
·
化学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2021
·
IF 3
Zong-Chao HONG,Quan CAI,He-Zhen WU,Yan-Fang YANG,Heng FAN,Xue-Yun DUAN
Ulcerative colitis (UC) is a chronic refractory non-specific intestinal inflammatory disease that is difficult to be cured. The discovery of new ulcerative colitis-related metabolite biomarkers may help further understand UC and facilitate early diagnosis. It may also provide a basis for explaining the mechanism of drug action in the treatment of UC. Compound Sophorae Decoction (CSD) is an empirical formula used in the clinical treatment of UC. Although it is known to be efficacious, its mechanism of action in the treatment of UC is unclear. The purpose of this study was to investigate the changes in endogenous substances in UC rats and the effects of CSD on metabolic pathways using the metabonomics approach. Metabolomics studies in rats with UC and normal rats were performed using LC-MS/MS. Rats with UC induced using TNBS enema were used as the study models. Metabolic profiling and pathway analysis of biomarkers was performed using statistical and pathway enrichment analyses. 36 screened potential biomarkers were found to be significantly different between the UC and the normal groups; it was also found that CSD could modulate the levels of these potential biomarkers. CSD was found to be efficacious in UC by regulating multiple metabolic pathways.
研究领域:
药理学
·
代谢组学
·
胃肠病学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2015
·Vol. 20
·期 11
·20031-20041
·
IF 2.416
Jie Zhao,Ting Geng,Qi Wang,Haihong Si,Xiaoping Sun,Qingming Guo,Yanjing Li,Wenzhe Huang,Gang Ding,Wei Xiao
Ginkgolide B (GB), an important active constituent ofGinkgo bilobaextract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18column (1.8 μm, 2.1 × 50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions atm/z(Q1/Q3) 423.1/367.1 for GB andm/z269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The Cmaxvalues of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations.Keywords:ginkgolide B;hot-melt extrusion;liquid layer;beagle dog plasma;pharmacokinetics;LC-MS/MS
研究领域:
药理学
·
药物分析
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 9
·1104
·
IF 5.215
Yin Huang,Fang Yang,Linling Guo,Yan Xu,Xiaxia Yu,Zunjian Zhang,Yuxin Zhang
Doxorubicin (DOX) is an essential component in chemotherapy, and Astragali Radix (AR) is a widely used tonic herbal medicine. The combination of DOX and AR offers widespread, well-documented advantages in treating cancer, e.g., reducing the risk of adverse effects. This study mainly aims to uncover the impact of AR on DOX disposition in vivo. Rats received a single intravenous dose of 5 mg/kg DOX following a single-dose co-treatment or multiple-dose pre-treatment of AR (10 g/kg × 1 or × 10). The concentrations of DOX in rat plasma and six tissues, including heart, liver, lung, kidney, spleen, and skeletal muscle, were determined by a fully validated LC-MS/MS method. A network-based approach was further employed to quantify the relationships between enzymes that metabolize and transport DOX and the targets of nine representative AR components in the human protein–protein interactome. We found that short-term (≤10 d) AR administration was ineffective in changing the plasma pharmacokinetics of DOX in terms of the area under the concentration–time curve (AUC, 1303.35 ± 271.74 μg/L*h versus 1208.74 ± 145.35 μg/L*h,p> 0.46), peak concentrations (Cmax, 1351.21 ± 364.86 μg/L versus 1411.01 ± 368.38 μg/L,p> 0.78), and half-life (t1/2, 31.79 ± 5.12 h versus 32.05 ± 6.95 h,p> 0.94), etc. Compared to the isotype control group, DOX concentrations in six tissues slightly decreased under AR pre-administration but only showed statistical significance (p< 0.05) in the liver. Using network analysis, we showed that five of the nine representative AR components were not localized to the vicinity of the DOX disposition-associated module. These findings suggest that AR may mitigate DOX-induced toxicity by affecting drug targets rather than drug disposition.Keywords:Adriamycin;drug disposition;combination therapy;LC-MS/MS;network
研究领域:
药理学
·
肿瘤学
·
中药学
·
分析化学
·
系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 15
·5634
·
IF 4.6
Chen Sun,Bo Liu,Fengzhi Zhou,Qianqian Zheng,Chunmei Dai,Wei Wei,Guochao Liao,Yuqi Sun
SARS-CoV-2 is a highly contagious and pathogenic virus that first appeared in late December 2019 and caused a global pandemic in a short period. The virus is a single-stranded RNA virus belonging to the Coronaviridae family. Numerous treatments have been developed and tested in response to the pandemic, particularly antiviral drugs. Among them, GS441524 (GS441), a nucleoside antiviral drug, has demonstrated promising results in inhibiting SARS-CoV-2. Nevertheless, the limited oral bioavailability of GS441 restricts its application to patients with the virus. In this study, a novel prodrug of GS441 (NGP-1) with an isobutyl ester and cyclic carbonate structure was designed and synthesized. Its purity and the stability in different artificial digestive juices of NGP-1 was determined with HPLC-DAD methods. The pharmacokinetics of NGP-1 and GS441 were studied in rats via gavage administration. A new LC-MS/MS method was developed to quantitatively analyze GS441 in plasma samples. The results showed that the ka, Cmax, and MRT of converted GS441 from NGP-1 were 5.9, 3, and 2.5 times greater than those of GS441 alone. The Frelof NGP-1 was approximately four-fold that of GS441, with an AUC0–∞of 9716.3 h·ng mL−1. As a prodrug of GS441, NGP-1 increased its lipophilicity, absorption, and bioavailability, indicating that it holds promise in improving the clinical efficacy of anti-SARS-CoV-2 medications.Keywords:anti-SARS-CoV-2;prodrug of GS441524;purity;stability and pharmacokinetics;oral bioavailability;LC-MS/MS
研究领域:
药理学
·
病毒学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2024
·
IF 2.8
Xijin Yang,Ying Li,Qiju Shao,Zhirong Li,Zeli Chun,Yan Wang,Yaping Zhou,Rongxiang Chen
Persicaria chinensis (L.) H. Gross ( P. chinensis ), also known as “Huotanmu” in Chinese, is a traditional ethnic herbal medicine and a functional food ingredient. In this study, liquid chromatography − electrochemical detection (LC-ECD) screening, liquid chromatography − tandem mass spectrometry (LC-MS/MS) identification, and multivariate statistical analysis were combined to clarify the antioxidant components in P. chinensis . The samples were extracted using 80 % aqueous methanol under ultrasound-assisted extraction and their in vitro antioxidant activities were evaluated. The fingerprint of P. chinensis was established using LC-ECD, while the identification of major chemical components was performed using LC-MS/MS through comparison of ion fragments. Subsequently, grey correlation analysis and partial least squares regression analysis were used to investigate the association of different compounds with antioxidant activity. P. chinensis from different sources showed excellent DPPH radical scavenging capacity, ABTS radical scavenging capacity, and ferric reducing antioxidant power. A total of 25 common peaks were obtained and identified in the LC-ECD fingerprint of P. chinensis , which were primarily comprised of tannins and flavonoids. The similarity between samples of different batches was ≥ 0.767, indicating relatively consistent quality. The comprehensive analysis results of grey relational analysis and partial least squares regression analysis indicated that tannins such as di-galloyl-HHDP-hexoside and davidiin were the major contributors to the antioxidant activity of P. chinensis . Therefore, LC-ECD can rapidly screen the potential phenolic antioxidants of P. chinensis , providing a basis for its product development, resource utilization, and quality control.
研究领域:
植物化学
·
药理学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2119
·
IF 4.9
Chengwei Wang,Chunjie Wu,Linjiang Song
Saiga antelope horn (SAH), a rare traditional Chinese medicine, exhibits activities of anti-feverish convulsions and anti-inflammation, whereas its underlying mechanism and specific pharmacological components are still unclear. In the present study, transient receptor potential ankyrin 1 (TRPA1), a major transient receptor potential cation channel was used as a target protein to identified TRPA1 high-affinity peptides (THPs) from SAH digests. Firstly, the SAH was digested under in vitro gastrointestinal conditions. With the method of affinity ultrafiltration and liquid chromatography–mass spectrometry (AUF-LC/MS), about 200 peptides that have a high-affinity interaction with the TRPA1 protein were screened from SAH digests. Subsequently, bioactivity databases and molecular docking were further exploited to identified three THPs, including RCWPDCR, FGFDGDF, and WFCEGSF. Furthermore, RIN-14B cells, characterized by the high expression of TRPA1 on cell surfaces, were used as the cell model to investigate the biological effect of THPs. Immunofluorescence and ELISA were conducted and showed that THPs can increase the intracellular Ca2+concentration and serotonin (5-HT) secretion in RIN-14B cells by activating TRPA1, which is evidenced by impaired upregulation of intracellular Ca2+levels and 5-HT secretion after pretreatment with the TRPA1 inhibitor (HC-030031). Moreover, an analysis of Western blots displayed that THPs up-regulated the expression levels of the 5-HT synthesis rate-limiting enzyme (TPH1) and 5-hydroxytryptophan decarboxylase (Ddc), while serotonin reuptake transporter (SERT) levels were down-regulated, suggesting that THPs enhance 5-HT secretion by regulating the 5-HT synthesis pathway. In summary, our findings demonstrate that THPs, which were identified from SAH digest via TRPA1-targeted affinity panning, exhibited the activation of the TRPA1 channel and enhanced 5-HT release in RIN-14B cells.
研究领域:
药理学
·
分子生物学
·
传统中药
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2021
·Vol. 10
·期 5
·1073
·
IF 4.35
Meng-Bo Tian,Lin Yuan,Ming-Yuan Zheng,Zhu-Mei Xi
Anthocyanins are vital components of plant secondary metabolites, and are also the most important coloring substances in wine. Teinturier cultivars are rich in anthocyanins. However, the differences in anthocyanin accumulation and profiles between teinturier and non-teinturier cultivars have not been reported. In this study, Yan 73 and Dunkelfelder were selected as the experimental materials, and three non-teinturier cultivars were used for comparison. LC-MS and qRT-PCR were used to determine the individual anthocyanin contents and the relative gene expression. The results show that the total anthocyanin content of the teinturier cultivars was considerably higher than that in non-teinturier cultivars, and the levels of individual anthocyanins increased gradually during ripening. Lower ratios of modified anthocyanins were found in the teinturier cultivars, which was not only due to the high expression level ofVvUFGTandVvGST4, but also due to the relatively low expression ofVvOMTin these cultivars. Cluster analysis of gene expression and anthocyanin accumulation showed thatVvUFGTis related to anthocyanin accumulation, and thatAM1is related to the synthesis and transport of methylated anthocyanins. Our results will be useful for further clarifying the pathways of anthocyanin synthesis, modification, and transport in teinturier cultivars.Keywords:grape;Yan 73;Dunkelfelder;anthocyanin;cluster analysis
研究领域:
植物学
·
植物生理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2024
·
IF 3.8
Baodong Feng,Linqi Su,Yang Yang,Renyan Liu,Yu Zhang,Lingyi Xin,Li Wang,Zhiming Yang,Xuemei Wei,Qinhua Chen
Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) influenced by multiple factors. Berberine, an isoquinoline alkaloid derived from the root and bark of Coptis chinensis Franch., has shown promise in managing UC, but its underlying mechanisms remain unclear.Methods: To elucidate the relationship between berberine, ulcerative colitis (UC), and the organism’s metabolome, we established a dextran sulfate sodium (DSS)-induced UC model in rats. Colonic tissue was collected for histopathological examination, while plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with dynamic Multiple Reaction Monitoring (dMRM). This approach, characterized by its short analysis time of 20 min per sample, excellent reproducibility, and straightforward data processing, allowed for the comprehensive detection of a wide array of metabolites, including amino acids, lipids, and organic acids, many of which are implicated in the pathophysiology of UC.Results: Our results showed that berberine modulated the metabolic disturbances of 33 compounds in the plasma of UC rats, primarily including amino acids, pyrimidines, organic phosphoric acids, fatty acyls, and organonitrogen compounds. These altered metabolites were associated with various pathways, such as amino acid metabolism, glutathione metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, pyrimidine metabolism, glyoxylate and dicarboxylate metabolism, and the citrate cycle (TCA cycle). Notably, 3-hydroxyproline, homocysteic acid, L-threonine, L-lysine, carbamoyl phosphate, O-phosphoethanolamine, taurine, leucine, and phosphorylcholine exhibited significant differences between the Treatment and Model groups, with levels reverting to those of the Control group (p < 0.001). These findings suggested that these compounds may serve as potential plasma biomarkers for UC.Conclusion: This study provided valuable insights into the mechanism by which berberine exerted its therapeutic effects on UC through metabolomics. Our results highlighted berberine’s potential to modulate key metabolic pathways and restore the levels of several metabolites, suggesting its utility as a therapeutic agent for UC. These findings underscored the importance of metabolomics in understanding the pathophysiology and treatment of UC.
研究领域:
药理学
·
代谢组学
·
炎症性肠病研究
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）