DRUG METABOLISM AND DISPOSITION
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2026
·
IF 3.6
Peng Li,Xianqing Yu,Jiamin Wu,Gengyao Qin,Hong Zhang,Weiqun Cao,Mingshe Zhu,Liang Shen,Yi Tao
Vutrisiran is a GalNAc-conjugated small interfering RNA (siRNA) therapeutic approved for targeted hepatic delivery and long-acting gene silencing; however, detailed in vitro and in vivo metabolism data have not been published. In this study, a sensitive LC–HRMS platform was established to systematically evaluate the metabolism and disposition of Vutrisiran in rats following administration of a low, pharmacologically relevant dose (3 mg/kg). Vutrisiran exhibited high systemic metabolic stability, with intact parent drug as the predominant species in plasma and urine. Tissue metabolite profiling revealed distinct organ-specific pathways, including hepatic GalNAc cleavage followed by slow 3′-exonuclease–mediated degradation, and a low abundant but unique kidney-specific 5′-truncation of the sense strand (SS 5′ n-4). Renal excretion was the primary route for elimination of intact drug, whereas biliary excretion was responsible for clearance of extensively catabolized fragments. The overall excretion pattern was consistent with that reported for other GalNAc-conjugated oligonucleotides. These rat metabolic profiling data provide insight into the disposition of Vutrisiran in humans and represent the first reported in vivo disposition characterization of Vutrisiran. The LC–HRMS platform developed in this study enabled highly sensitive metabolite profiling and identification. A semi-quantitative approach based on MS peak area integration was validated by demonstrating close numerical agreement with UV detection. This platform supports metabolite profiling in plasma and target tissues for PK/PD studies and rapid disposition characterization in animals and may serve as an alternative or pilot approach to inform the design and necessity of human radiolabeled mass-balance studies for oligonucleotide therapeutics.
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Lijun Liu,Junhui Chen,Xiuping He,Shuang Hao,Ziru Lian,Baodong Wang
Paralytic shellfish poisoning (PSP) toxins have received considerable attention in recent years because of their adverse effects on marine breeding industries and human health. In this study, a reliable method for the analysis of extracellular PSP toxins in the culture medium of marine toxic dinoflagellates was developed for the first time using graphitized carbon black–solid-phase extraction and hydrophilic interaction liquid chromatography–high-resolution mass spectrometry. The limit of quantification of typical PSP toxins in algal culture medium ranged from 0.072 μg/L to 0.151 μg/L under optimal conditions. Satisfactory absolute recoveries (87.5%–102.4%), precision (relative standard deviation ≤ 7.6%), and linearity ( R 2 ≥ 0.9998) were also achieved. In addition, the proposed method was applied to screen and determine the extracellular PSP toxins of two typical toxigenic dinoflagellates, Alexandrium minutum and Alexandrium tamarense . The total concentrations of the extracellular PSP toxins in A. minutum and A. tamarense over the whole growth period were within 2.0–735.5 and 2.0–19.2 μg/L, respectively. The concentrations of extracellular PSP toxins varied remarkably in the different growth stages of A. minutum and A. tamarense , and the contents of some extracellular PSP toxins were substantially higher than those of intracellular PSP toxins. Therefore, the extracellular PSP toxins released by toxigenic red tide algae cannot be ignored, and their environmental fate , bioavailability , and potential harm to aquatic environment need to be investigated in future studies.
研究领域:
海洋生物学
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环境科学
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分析化学
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PubMed
高影响因子
CHEMOSPHERE
·
2020
·
IF 5.778
Chuang Fu,Xianliang Yi,Yang Liu,Hao Zhou
Sulfonamide antibiotics (SAs) are widely used in veterinary medicine but are poorly metabolized in biological systems; thus, they can cause a selective pressure to promote the proliferation of antibiotic resistant pathogens and threaten human health. Persulfate (PS)-based advanced oxidation processes (AOPs) have been applied for SA degradation, but using transition metal ions as PS activators is relatively limited. In this study, sulfamethazine (SMZ) was used as a model SA to evaluate the performance of a Cu 2+ -activated PS system. Cu 2+ -PS exhibited better SMZ removal than other metal ions, and 25 mg/L SMZ can be degraded in the presence of 0.2 mM Cu 2+ and 2.5 g L −1 PS within 120 min. Various anions inhibited SMZ degradation to different degrees except HCO 3 − . Among the cations, Fe 3+ significantly inhibited SMZ removal, while Ni 2+ increased the removal rate. High concentrations of humic acid and protein also increased the degradation rate of SMZ. Radical and singlet oxygen quenching experiments, together with the results of electron spin-resonance spectroscopy (ESR), showed that the main active species generated from Cu 2+ -PS are SO 4 · - and ·OH. The degradation pathway of SMZ was identified through HPLC-HRMS. Direct SO 4 · - and ·OH oxidation products of SMZ were not found, suggesting that the complex formed between Cu 2+ and SMZ may affect the fate of SMZ. On the other hand, the efficiency and selectivity of Cu 2+ -PS against different SAs were confirmed. Overall, this study provides a facile and effective method for SMZ and other SA removal.
研究领域:
环境科学
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化学工程
·
水处理
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PubMed
高影响因子
JOURNAL OF FOOD AND DRUG ANALYSIS
·
2021
·
IF 6.079
Wei Jia,Yuyang Liu,Xi Xu,Yanxi Zhang,Lin Shi
A novel magnetic adsorbent solid-phase Fe 3 O 4 @ZIF-8 extraction method coupled with UHPLC Q-Orbitrap high resolution mass spectrometry for the sensitive and high efficiency detection of fluoroquinolones, tetracyclines, dyes and amphenicols in eggs is described. Under optimum conditions, CCβ and CCα of 0.62 to 26.97 μg.kg −1 and 0.36 to 16.37 μg.kg −1 was obtained, which is much better than that obtained by conventional methods. The accuracy, expressed as recovery, were achieved falling between 75% and 104%. The proposed strategy provides several advantages of simplicity and low energy consumption, thus retaining potential for the screening of risky drugs in various samples.
研究领域:
分析化学
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食品安全
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生物医学
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PubMed
高影响因子
FOOD CHEMISTRY
·
2026
·
IF 10.4
Xinrui Yang,Xiaoling Chen,Gaohan Li,Yang Zhou,Qinhua Chen,Jinjun Hou,Changwu Zheng,Zijia Zhang,Wanying Wu
Areca nut ( Areca catechu L.) is a widely consumed food and medicinal plant with both nutritional value and documented health risks. To comprehensively characterize its chemical composition and spatial distribution, we developed an integrated analytical platform combining solid-phase extraction (SPE), offline two-dimensional liquid chromatography with high-resolution mass spectrometry (2D-LC-HRMS), and desorption electrospray ionization mass spectrometry imaging (DESI-MSI). This approach enriched trace constituents while minimizing matrix interference, enabling the identification of 323 compounds-including terpenes and triterpenoids (89), alkaloids (52), flavonoids (31), lignans (17), and steroids (12). A pH-orthogonal separation system (alkaline and acidic modes) significantly improved resolution of structurally similar, low-abundance compounds. Spatial analysis via DESI-MSI revealed three distribution patterns: seed-specific enrichment, pericarp enrichment, and uniform distribution. By integrating compositional and spatial data, this study offers new insights into the pharmacological basis, potential toxicity mechanisms, and safe applications of areca nut in food systems.
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高影响因子
Drug Design Development and Therapy
·
2020
·
IF 3.216
Xiaofang Jiang,Lin Zhou,Lihua Zuo,Xiaohui Wang,Yingying Shi,Xiangyu Du,Jun Zhang,Liwei Liu,Zhuolun Li,Lianping Xue,Xin Liu,Zhi Sun
Purpose Shenkang injection, a traditional Chinese herbal prescription, had been widely used in renal disease due to its perfect curative effect. In this research, a novel, sensitive, accurate and rapid liquid chromatography-tandem mass spectrometric method was developed to simultaneously detect the seven active ingredients in rat plasma of Shenkang injection and investigate its pharmacokinetic behaviors with metabolism profiling meanwhile.Methods For accurate pharmacokinetic quantitation, a WATERS ACQUITY UPLC® BEH C18 column was used to perform a separation and acetonitrile-water (0.1% formic acid) was selected as mobile phase for gradient elution with a flow rate of 0.20 mL/min. A heated electrospray ionization with selective reaction monitoring mode was used to monitor the precursor-product ion transitions for all the analytes and IS.Results They all showed good linearity over a wide concentration range (r>0.996 3) and the lower limit of quantification (LLOQ) was 0.1–1.0 ng/mL for analytes. The validation parameters were all within the acceptable limits. Furthermore, for metabolism profiling study, metabolites of the seven ingredients were identified from the rat plasma based on the accurate mass and fragment ions. The metabolic pathways mainly focus on reduction, dehydration and conjugation.Conclusion This study provided an overview of disposition of Shenkang injection, which is highly instructive for better understanding the effectiveness and toxicity of this drug.
研究领域:
中药学
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药理学
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分析化学
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PubMed
高影响因子
MICROCHIMICA ACTA
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2020
·Vol. 187
·期 2
·1-11
·
IF 6.232
Di Siyuan,Yu Jing,Chen Pin,Zhu Gangtian,Zhu Shukui
A net-like mesoporous carbon nanocomposite (MCN) was hydrothermally prepared by using filter paper as the raw material. The MCN contains magnetic nanoparticles of type Fe 3 O 4 which result from the addition of Fe(NO 3 ) 3 ·9H 2 O during synthesis. The MCN was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, Raman spectra, Brunauer-Emmett-Teller methods and vibrating sample magnetometry. The MCN is shown to be a viable material for magnetic solid-phase extraction of trace sulfonamides (SAs) including sulfadiazine, sulfapyridine, sulfamerazine, sulfamethazine, sulfamethizole, sulfamethoxypridazine, sulfachloropyridazine and sulfadimethoxine. Following desorption with acetone containing 0.5% ammonia, the SAs were quantified by UPLC with high-resolution mass spectrometric detection. With sulfamethazine as an example, the adsorption equilibrium configurations and the major interaction mechanism between SAs and the MCN were calculated by using density functional theory. Under the optimal conditions, the calibration plots are linear in the 0.05–10 ng·mL −1 SA concentration ranges. The limits of detection are between 7.2 and 13.6 ng·L −1 . The recoveries from spiked samples ranged from 79 to 107%, with relative standard deviations of <9.9%.
Schematic representation of nanocomposite preparation, adsorption mechanism of sulfonamide and magnetic solid-phase extraction (MSPE) for sulfadiazine (SDZ), sulfapyridine (SPD), sulfamerazine (SMR), sulfamethazine (SMZ), sulfamethizole (SMT), sulfamethoxypridazine (SMP), sulfachloropyridazine (SCP) and sulfadimethoxine (SDMX). Quantification was accomplished by UPLC with high-resolution mass spectrometric detection
研究领域:
分析化学
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环境科学
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PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Yuqing Zhao,Yue Yang,Mingshe Zhu,Chongzhuang Tang
Metabolite profiling and identification of oligonucleotide-based therapeutics (OBTs) is important in drug discovery and development. Conventional liquid chromatography-high resolution mass spectrometry (LC-HRMS) methods (using ProMass, BioPharma Finder) are effective for targeted analysis of predictable nuclease-derived metabolites but often miss unexpected non-nuclease-mediated ones. This study aimed to develop a universal analytical workflow for comprehensive metabolite profiling of multiple classes OBTs by integrating BioPharma Finder for targeted identification with a Background Subtraction Filter (BSF) for untargeted detection of unexpected biotransformation products. Inclisiran, a GalNAc-conjugated siRNA, was used as a model compound. Samples incubated with rat, monkey, and human liver S9 fractions were analyzed by the LC-HRMS workflow. As a result, a total of 25 (22 predicted +3 unpredicted) inclisiran metabolites were identified across the three species. BioPharma Finder enabled rapid and sensitive identification of 22 predicted metabolites, supported by automated fragment ion assignment. The BSF data processing revealed 22 metabolites not present in control samples, including SS-1GalNAc, SS-2GalNAc, and SS-3GalNAc, which were missed by BioPharma Finder and likely formed via β- N -acetylglucosaminidase-mediated biotransformation. The structures of BSF-detected metabolites were confirmed by comparison with BioPharma Finder-identified metabolites or characterized through manual MS/MS interpretation. Product ion spectra of these metabolites showed weak or absent diagnostic ion ( m / z 94.936), a characteristic fragment of phosphorothioate-containing oligonucleotides, suggesting that the product ion filtering of this ion exhibits limited utility in discovering inclisiran metabolites. Overall, the integrated LC-HRMS workflow shows strong potential as a universal platform for biotransformation studies of OBTs.
研究领域:
药物分析
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代谢组学
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药物代谢
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生物治疗
·
质谱分析
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寡核苷酸治疗
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PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Jingyu Li,Yuping Zhang,Renyu Zhang,Rujie Yang,Qianli Ma,Zhongshuai Wang,Pi Li,Jiangtao Xing,Peng Gao,Huan Liu,Hansheng Gong
Lipids are the key matrix for the presence of odorants in meat products. The formation mechanism of odorants of air-fried (AF) pork at 230 °C was elucidated from the perspectives of lipids and heat transfer using physicochemical analyses and multidimensional statistics. Twenty-nine key aroma compounds were identified, with pyrazines predominantly contributing to the roasty aroma of air-fried roasted pork. Untargeted lipidomics revealed 1184 lipids in pork during roasting, with phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triglyceride (TG) being the major lipids accounting for about 60 % of the total lipids. TG with C 18 acyl groups, such as TG 16:1_18:1_18:2 and TG 18:0_18:0_20:3, were particularly significant in forming the aroma of AF pork. The OPLS-DA model identified seven potential biomarkers that differentiate five roasting times, including PC 16:0_18:3 and 2-ethyl-3,5-dimethylpyrazine. Notably, a lower specific heat capacity and water activity accelerated heat transfer, promoting the formation and retention of odorants in AF pork.
研究领域:
食品科学
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分析化学
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DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2018
·Vol. 164
·期 6
·427-435
·
IF 2.35
Xu Tanye,Zhou Lin,Shi Yingying,Liu Liwei,Zuo Lihua,Jia Qingquan,Du Shuzhang,Kang Jian,Zhang Xiaojian,Sun Zhi
Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction. Metabolomic profiling in bio-fluid or tissue is vital for elucidating the pathogenesis of sepsis and evaluating therapeutic effects of medication. In this study, an untargeted metabolomics approach was applied to study the metabolic changes in lung tissue of septic rats induced by cecal ligation and puncture (CLP) and investigate the treatment effects of Xubijing injection (XBJ). Metabolomics analyses were performed on ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap-HRMS) together with multivariate statistical analysis. A total of 26 differential metabolites between CLP and sham-operated group were identified. The altered metabolic pathways included energy metabolism, amino metabolism, lipid metabolism, fatty acid metabolism and hormone metabolism. Among the 26-varied metabolites, 15 were significantly regulated after XBJ treatment. The metabolic pathway network of sepsis was drawn to interpret the pathological feature of lung damage caused by sepsis and the underlying regulating mechanism of XBJ on the molecular levels. Our findings display that LC-MS-based metabolomics is a useful tool for uncovering the underlying molecular mechanism of sepsis, and XBJ may exert therapeutic effect by regulating multiple metabolic pathways.
研究领域:
医学
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药理学
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生物化学
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2024
·
IF 2.8
Peng Wang,Qiuliang Xu,Hua Zou,Ming Liu,Xiangjing Gao,Hong Ren,Junlin Wang,Yiyao Cao
Accurate, reliable, and sensitive methods for the determination of eight metabolites of p-chloronitrobenzene (p-CNB) were developed based on ultra-performance liquid chromatography − quadrupole − orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). The free and conjugated forms of metabolites were determined before and after urine samples were hydrolyzed with acid. Subsequently, three solid phase extraction steps were used for concentration and purification. The calibration curves of the eight metabolites exhibited good linearity with an R 2 of >0.999, and the precision was good as well, with the coefficient of variations of intra-day and inter-day being lower than 7.0 % and 8.5 %, respectively. Analytical accuracy for all metabolites varied within ranges of 76.0–102.9 %, and the limit of detection and limit of quantification of all the metabolites varied within ranges of 0.2–7.7 μg/L and 0.6–25.6 μg/L in human urine, respectively. In addition, the application potential of the proposed methods were evaluated by applying them to the determination of metabolites in the urine of workers exposed to p-CNB, and these results showed that these methods were accurate, reliable, and sensitive, which makes them an excellent choice for detecting the metabolites of p-CNB in the urine of exposed workers.
研究领域:
分析化学
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环境健康
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职业健康
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2024
·
IF 2.8
Tong Zhang,Zhuoqian Guo,Tao Ma,Shanlan Li,Ziqi Dai,Yujin Luo,Feng Gao,Qi Zeng,Jihui Lu,Junshuai Wang,Yongli Liu,Bing Xu,Haimin Lei
Qingfei Decoction (QFD) is recognized as one of the 100 classic prescriptions by the National Administration of Traditional Chinese Medicine of China and is widely used for the treatment of pulmonary diseases. Chronic obstructive pulmonary disease (COPD) is a common respiratory condition primarily characterized by airway obstruction. It’s necessary to examine the therapeutic effect of QFD in the treatment of COPD and elucidate its potential effective components, targets, and pathways. This study utilized UHPLC coupled with HRMS to identify the chemical constituents of QFD, resulting in the qualitative analysis of 68 compounds. Network pharmacology predicted 30 gene targets, including IL6, AKT1, and EGFR, and revealed 45 compounds, including ruscogenin, schisandrin A, and esculetin that may contribute to its therapeutic effects on COPD. Subsequently, an elastase-induced COPD mouse model was employed to evaluate the efficacy of QFD. The effects of QFD were assessed through hematoxylin and eosin (H&E) staining, periodic acid-Schiff (PAS) staining, and real-time quantitative polymerase chain reaction (RT-qPCR) on lung tissues. Transcriptomic analysis indicating QFD treatment of COPD primarily acted on the IL-17 signaling pathway, which was consistent with the network pharmacology results. Furthermore, RT-qPCR, immunofluorescence, and western blot demonstrated reduced mRNA and protein expression levels of TRAF3IP2, TRAF6, IL17, and TNFα. These findings confirmed that QFD effectively reduced inflammation, likely by down-regulating the IL-17 signaling pathway, thereby treating COPD.
研究领域:
中医药学
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药理学
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呼吸系统疾病
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分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）