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JOURNAL OF CHROMATOGRAPHIC SCIENCE · 2019 ·Vol. 58 ·期 1 ·31-36 · IF 1.216

The Chiral Bioconversion and Pharmacokinetic Analysis of Trelagliptin in Beagle Dog Plasma by LC–MS/MS

Zhou Li,Xi Wang,Zhang Hui,Sun Lili,Yu Jinlong,Zou Qiaogen

A simple and enantioselective method was developed and validated for the simultaneous determination of (R)- and (S)-trelagliptin in beagle dog plasma by chiral liquid chromatography tandem mass spectrometry. Trelagliptin enantiomers and (R)-rabeprazole (as internal standard, IS) were extracted from plasma samples by liquid–liquid extraction and separated on a CHIRALCEL OX-3R column using acetonitrile-5 ammonium bicarbonate as the mobile phase in gradient elution mode. The multiple reactions monitoring transitions of m/z 358.1→341.2 and 359.9→150.1 were used to quantify trelagliptin enantiomers and IS, respectively. This method was validated for sensitivity, specificity, linearity, precision, accuracy and stability of specific analytes under various conditions. And it was successfully applied to evaluating the pharmacokinetic profile of trelagliptin enantiomers in beagle dogs after single intravenous administration of (R)-trelagliptin injection (at 1 mg/kg) and oral administration (at 6.7 mg/kg). In this study, no chiral bioconversion of (R)-trelagliptin to (S)-trelagliptin in beagle dog plasma was observed. The absolute bioavailability of (R)-trelagliptin was identified to be 128.2%.

CAS / MDL: 631-61-8
研究领域: 药物分析 · 药理学
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TALANTA · 2019 · IF 4.916

Development of Molecularly Imprinted 2D Photonic Crystal Hydrogel Sensor for Detection of L-Kynurenine in Human Serum

Aysha Sarfraz Rizvi,Ghulam Murtaza,Dan Yan,Muhammad Irfan,Min Xue,Zi Hui Meng,Feng Qu

l -Kynurenine (KYN) is a metabolite of the Kynurenine pathway and is a known potential marker of immune suppressant disorders and cancer. Here, we present a molecularly imprinted two dimensional (2D) Photonic crystal (PC) hydrogel sensor for the detection of L-KYN in human serum. The sensor utilizes polystyrene-based 2D PC colloidal arrays (2D PCCA) hydrogel with methacrylic acid as the functional monomer which can imprint the L-KYN template by hydrogen bonding . After removal of the template, the resulting nanocavities in the hydrogel can selectively bind and recognize L-KYN in the serum samples. The binding is selective for L-KYN, which is revealed by shrinkage of the hydrogel volume and decrease in the particle spacing that can be easily monitored through changes in the Debye diffraction ring diameter using a LASER pointer. The sensor demonstrates visible red to green color shift upon binding to L-KYN. The 2D PC sensor demonstrates the limit of detection (LOD) of 50  nM, linear relationship of particle spacing versus L-KYN concentration range (50–1000  nM) with the analytical recovery of up to 92 % in the spiked serum samples. The sensor can distinguish between L-KYN and D-KYN and is re-usable up to five times. The sensor is available for the rapid and quantitative detection of L-KYN in the human serum.

CAS / MDL: 79-41-4 100-42-5
研究领域: 生物化学 · 医学诊断 · 材料科学
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RSC Advances · 2017 ·Vol. 7 ·期 45 ·28016-28023 · IF 3.108

Blue and cyan fluorescent carbon dots: one-pot synthesis, selective cell imaging and their antiviral activity

Huabing Liu,Yanli Bai,Yanrong Zhou,Chenchen Feng,Lingzhi Liu,Liurong Fang,Jiangong Liang,Shaobo Xiao

Carbon dots (CDs) have demonstrated attractive potential in cell imaging and tracking. However, one of the most challenge problems is the selective entrance of CDs into the cytoplasm or cell nucleus. Here, a facile strategy was developed to prepare two types of CDs capable of selective entrance into cytoplasm and the whole cell without further surface modification. The surface charge of CDs changes from negative to neutral after the addition of urea in the hydrothermal process, and the as-prepared CDs exhibit different fluorescent colors. The blue-fluorescent CDs (b-CDs) can only enter the cytoplasm, while the cyan-fluorescent CDs (c-CDs) can distribute over the whole cell, including the nucleus. Additionally, the antiviral activity of the two CDs against pseudorabies virus (PRV) was studied and b-CDs were shown to have better antiviral activity. This study has provided a facile and novel strategy for the fabrication of CDs used in selective cell imaging, which may facilitate the application of CDs in nanomedicine.

研究领域: 生物医学 · 纳米医学 · 病毒学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 8 ·3764 · IF 4.9

Tandemly Repeated G-Quadruplex Structures in the Pseudorabies Virus Genome: Implications for Epiberberine-Based Antiviral Therapy

Songjie Fan,Xiaotian Chang,Yan Qiao,Xiaoxiao Zhao,Jiafu Zhao,Heshui Zhu,Yingqian Han,Chao Zhang

G-quadruplex (G4) structures have emerged as critical regulatory elements in viral genomes and represent potential targets for antiviral intervention. In this study, we identified and characterized G4 structures in the unique long (UL) region of the Pseudorabies virus (PRV) genome, highlighting their role as novel antiviral targets. Bioinformatic analysis revealed two guanine-rich regions (R1 and R2) that form stable G4 structures, as confirmed by fluorescence assays, circular dichroism (CD) spectroscopy, and immunofluorescence staining. Notably, these G4 structures exhibit a tandem repeat arrangement, a previously unreported feature in the PRV genome. Epiberberine (EPI), a natural G4-stabilizing ligand, bound to and stabilized these structures, leading to the inhibition of Taq polymerase progression. Functional assays demonstrated that EPI effectively suppressed PRV replication in vitro while having no significant impact on viral entry or release. In vivo, EPI treatment significantly improved survival rates and reduced viral loads in multiple organs, including the brain, heart, lungs, and kidneys of infected mice. These findings provide new insights into the role of G4 structures in PRV replication and demonstrate that EPI exhibits potential antiviral activity by targeting G4 structures.

研究领域: 分子生物学 · 病毒学 · 药理学
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Frontiers in Pharmacology · 2025 · IF 4.8

UPLC-MS/MS method for simultaneous determination of pyrantel, praziquantel, febantel, fenbendazole and oxfendazole in dog plasma and its application to a bioequivalence study

Fengyichi Zhang,Fanxi Guo,Xinyu Zhao,Chongyang Li,Junli Wang,Mengyun Wang,Ruixia Ma,Baochang Chen,Qiangqiang Miao,Yimeng Wang,Zihan Wang,Di Cao,Zugong Yu

A rapid, sensitive and reliable ultra–performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was developed and validated for the simultaneous quantitation of pyrantel (PYR), praziquantel (PRA), febantel (FBT) and its active metabolites, fenbendazole (FEN) and oxfendazole (OXF) in dog plasma. Fenbendazole–D3 (FEN–D3) was used as an internal standard (IS). The analytes and IS were prepared using simple protein precipitation (PP) combined with liquid–liquid extraction (LLE). Chromatographic analysis was performed on UPLC BEH C18 column using acetonitrile–0.1% formic acid in water for gradient elution. Detection was carried out in multiple reaction monitoring (MRM) mode under positive electrospray ionization. The standard curves were linear through the concentration range of 4–240 ng/mL for PYR and OXF, 15–900 ng/mL for PRA, 2–120 ng/mL for FBT and 10–600 ng/mL for FEN with all correlation coefficients >0.99. The intra–and inter–batch precision was 1.08%–14.26% and accuracy was from 90.66% to 110.28%. The mean extraction recoveries for the analytes and IS were >90%. The total run time was 9.0 min. The developed method was successfully applied to a bioequivalence study after oral administration of compound febantel tablets in 38 healthy dogs.

CAS / MDL: 1336-21-6
研究领域: 兽医学 · 分析化学
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Current Research in Microbial Sciences · 2025 · IF 5.8

Canine-derived Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 combat aging by regulating gut microbiota

Nan Chen,Zexu Yu,Xuan Ji,Siyi Zhang,Chongwei Yu,Teresa G. Valencak,Fushan Shi,Daxi Ren

Old age raises the susceptibility of age-related disease in domestic dogs. Discovering effective anti-aging interventions is key for mitigating age-related disease and conserving “healthspan” in pet dogs. In this study, 2 bacterial strains were isolated from canine feces. After screening and identifying the strains, Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 were chosen to intervene during D- galactose-induced senescence in mice. We found that administering Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 improved the aging phenotype of mice, including an increase in antioxidant activity, a decrease in pro-inflammatory cytokines, and the restoration of intestinal and liver tissue damage. In addition, Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 lead to changes in the structure of intestinal microbiota in aging mice. Specifically, there was a decrease in the abundance of the Cyanobacteria and an increase in the abundance of Akkermansia and Lactobacillus . More importantly, there was a significant increase in acetic acid, a short-chain fatty acid, due to intervention with the 2 strains. This increase might be attributed to higher Akkermansia . We show that the modulation of gut microbiota and metabolism in aging mice may be a promising strategy through which Weissella confusa ZJUIDS-D034 and Enterococcus faecalis ZJUIDS-D016 might exert their anti-aging effects.

CAS / MDL: 7664-38-2
研究领域: 微生物学 · 老年医学 · 动物健康
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MOLECULES · 2018 ·Vol. 23 ·期 12 ·3214 · IF 3.098

Tailor-Made Deep Eutectic Solvents for Simultaneous Extraction of Five Aromatic Acids from Ginkgo biloba Leaves

Jun Cao,Huimin Wang,Wei Zhang,Fuliang Cao,Geli Ma,Erzheng Su

Ginkgo bilobaleaves have various health benefits due to the presence of bioactive compounds such as polyprenyl acetates, flavonoids, and terpene trilactones. However, there is little literature reported on the aromatic acids inGinkgo bilobaleaves. In this work, five aromatic acids including shikimic acid (SA), 6-hydroxykynurenic acid (6-HKA), protocatechuic acid (PA), gallic acid (GAA), andp-hydroxybenzoic acid (PHBA) were simultaneously extracted fromGinkgo bilobaleaves by employing the green deep eutectic solvents (DESs). A DES tailor-made from xylitol, glycolic acid and 1,5-pentanedioic acid at a molar ratio of 1:3:1 with 50% (w/w) water addition, named as NGG50, gave higher extraction yields for the five aromatic acids. Main factors affecting the extraction process were further optimized. The highest extraction yields of SA, GAA, 6-HKA, PA, and PHBA were 94.15 ± 0.96 mg/g, 332.69 ± 5.19 μg/g, 25.90 ± 0.61 μg/g, 429.89 ± 11.47 μg/g and 67.94 ± 0.37 μg/g, respectively. The NGG50-based extraction process developed here was a successful attempt of simultaneously extracting five aromatic acids fromGinkgo bilobaleaves for the first time, which could provide a new exploitation direction ofGinkgo bilobaleaves.Keywords:deep eutectic solvents;Ginkgo bilobaleaves;simultaneous extraction;shikimic acids;6-hydroxykynurenic acid

研究领域: 药学化学 · 分析化学 · 植物科学
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Current Pharmaceutical Analysis · 2023 ·Vol. 19 ·期 4 ·282-288 · IF 0.6

Synthesis, Structure Confirmation of Deuterium-substituted Kynurenine and the Conformation Analysis of Kynurenine in Daptomycin

Zhang Hanzhi,Qin Feng,Sun Ning,Zheng Mengmeng,Luo Wenyan,Qiu Ya,Liu Hao,Zhang Xiangmin

Background: After the hydrolysis of daptomycin in deuterated hydrochloric acid, the deuterium-substituted kynurenine was found, but the structure of deuterium-substituted kynurenine has not been reported. Introduction: The deuterium-substituted kynurenines were simply synthesized and confirmed to be tri- and tetra-substituted products by high resolution mass spectrum and NMR. In further, the deuterium-substituted kynurenines were used to determine the conformation of kynurenine to be L-type in daptomycin through conformation analysis combined with derivation and high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLCQ/ TOF-MS). Methods: In the present study, a simple synthesis method was developed for deuteriumsubstituted kynurenine, and its structure was confirmed by high resolution mass spectrometry and NMR. L-kynurenine was mixed with the deuterated hydrochloric acid and heated at 110 °C for 7 h. The hydrogen/deuterium exchange products of L-kynurenine were obtained through the hydrogen/deuterium exchange method. After the derivation of deuterium-substituted L-kynurenine by Marfey’s reagent, the conformation of kynurenine in daptomycin was deduced by HPLC-Q/TOF-MS. Results: The deuterium-substituted kynurenines were confirmed to be tri- and tetra-substituted products by high resolution mass spectrum. Further, Hydrogen NMR spectrum indicated that the deuterium-substitution positions were β-position on amino acid and 3’ and 5’ positions on the benzene ring. Thus, the tri-deuterium-substituted product was L-[β, 3’, 5’-2H3] kynurenine-d3, while the tetra-deuterium-substituted product was L-[β, β, 3’, 5’-2H4] kynurenine-d4. Furthermore, the deuterium-substituted kynurenines were used to determine the conformation of kynurenine to be L-type in daptomycin through conformation analysis combined with derivation and HPLC-Q/TOF-MS. Conclusion: The synthesis, structures, and application of tri- or tetra- deuterium-substituted kynurenine were reported in this study.

研究领域: 生物化学 · 药物化学 · 分析化学
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Natural Product Communications · 2025 · IF 1.4

Cerebral Ischemia Increases the Distribution and Residence Time of 6-Hydroxykynurenic Acid in the Ischemic Cerebral Cortex of Mice

Zhuowei Shen,Yanhong Chen,Kui Zeng,Haihong Hu,Jie Pan,Mingcheng Xu,Kaifeng He,Fengting Ou,Lushan Yu,Su Zeng,Lu Chen

Background6-hydroxykynurenic acid (6-HKA), isolated from Ginkgo biloba leaves, has demonstrated neurorestorative properties against cerebral ischemia in middle cerebral artery occlusion (MCAO) mice models. However, our previous studies showed that 6-HKA was difficult to penetrate the blood brain barrier (BBB) to exert its pharmacological effects in rats. Therefore, this study aims to investigate the pharmacokinetics and cerebral cortex distribution of 6-HKA in MCAO mice, to determine whether the ability of 6-HKA to cross the BBB is contingent upon barrier integrity.MethodsThis study established and validated the ultra-performance liquid chromatography tandem mass spectrometric (UPLC-MS/MS) methods for the quantification of 6-HKA in mouse plasma and brain, and investigated the pharmacokinetics and cerebral cortex distribution of 6-HKA in MCAO mice and sham-operated mice.ResultsThis study demonstrates that the mean residence time (MRT0−t) of 6-HKA in the MCAO group was significantly prolonged compared to the sham-operated group, and there was a higher distribution of 6-HKA in the ischemic cerebral cortex than in the contralateral normal cerebral cortex.ConclusionThis study illustrated that in MCAO mice, the prolonged MRT0−t of 6-HKA and the increased permeability of BBB made the accumulation of 6-HKA in the ischemic cerebral cortex, thereby enabling 6-HKA to exert neurorestorative effects.

研究领域: 神经科学 · 药理学 · 生物化学
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BIOMEDICAL CHROMATOGRAPHY · 2014 ·Vol. 28 ·期 12 ·1738-1743 · IF 1.662

Bioavailability comparison of a new form of vilazodone XVII to IV in beagles using liquid chromatography/mass spectrometry

Ling-ling Zeng,Li-li Sun,Qiaogen Zou,Fan Zhou,Ping Wei,Ping-kai Ouyang

Vilazodone hydrochloride (CAS 163521-12-8) is polymorphic and has 15 crystal forms, referred to as I–XI and XIII–XVI. In the study, we prepared and performed structural identification of a new crystal form named XVII. To investigate this in vivo , a rapid and sensitive method based on liquid–liquid extraction, followed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the determination of vilazodone hydrochloride in dog plasma. This HPLC-MS/MS method was successfully applied to a bioavailability comparison of two crystal forms of vilazodone hydrochloride (IV and XVII) in six healthy beagles using a single-dose, two-way crossover design. The maximum plasma concentration ( C max ), the time taken to reach C max , and the area under the concentration–time curve were determined following oral administration of 10 mg vilazodone hydrochloride (IV or XVII) to beagles. These analyses revealed no significant bioavailability differences between vilazodone hydrochloride forms IV and XVII in dogs. Copyright © 2014 John Wiley & Sons, Ltd.

CAS / MDL: 631-61-8
研究领域: 药学 · 分析化学
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ACS Nano · 2025 · IF 16

Metal–Phenolic Network Hydrogel Vaccine Platform for Enhanced Humoral Immunity against Lethal Rabies Virus

Jiamin Deng,Zongmei Wang,Liqin Wu,Zhiyong Song,Hagar Shendy Bahlol,Xun Li,Ling Zhao,Heyou Han

Rabies, caused by rabies virus (RABV), is a zoonotic disease with a high mortality rate that has attracted global attention with the goal of eradication by 2030. However, rabies can only be prevented by appropriate and multiple vaccinations, which impede widespread vaccination in developing countries due to its high expenditure. Designing single-dose vaccines is a pressing challenge in the prevention of rabies and other infectious diseases. Herein, a metal–phenolic network (MPN)-based hydrogel vaccine (designated as CGMR) was developed to stimulate potent humoral immunity against RABV infection by a single immunization, resulting in 4.3-fold and 1.8-fold enhancements of virus-neutralizing antibody compared with that induced by inactivated RABV and alum adjuvant. The CGMR, cross-linked by phenol-modified chitosan with manganese ion, could prolong residence time by confining the antigen to the network of hydrogel, acting as a “hydrogel antigen depot”. It also stimulated the activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway, facilitating dendritic cell maturation and antigen presentation. The vaccine formulation recruited immunocytes and activated the germinal center, enhancing and sustaining humoral immune responses against the virulent RABV challenge. Collectively, this injectable manganese-based hydrogel vaccine provides a universal and ideal avenue for rabies and other infectious diseases.

研究领域: 免疫学 · 生物医学工程 · 病毒学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2012 · IF 2.453

Adjuvant activity of Chinese herbal polysaccharides in inactivated veterinary rabies vaccines

Ye Liu,Shoufeng Zhang,Fei Zhang,Rongliang Hu

Four botanical polysaccharide preparations (from Astragalus , Echinacea , wolfberry, and kelp) were evaluated as immunopotentiators/adjuvants of a veterinary rabies vaccine. Results showed that lymphocyte proliferation and some cytokines were significantly elevated, with cellular immune responses skewed towards Th1 and Tc1. All four polysaccharides produced accelerated and enhanced effects on rabies-neutralizing antibody responses in mice and dogs. The results also indicated that certain botanical polysaccharides could be used in rabies vaccine formulations for early and persistent prophylaxis.

研究领域: 免疫学 · 兽医学 · 植物化学
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