TALANTA
·
2025
·
IF 6.1
Xian Li,Xinxin Wen,Zewei Luo,Xuejun Wang,Yilin Zhang,Jing Wei,Yonghui Tian,Rui Ling,Yixiang Duan
Breast cancer (BC) is the primary cause of cancer-related deaths in women. Currently, the discovery of biomarkers primarily relies on single platform, which might overlook other potential biomarkers and lead to inaccurate diagnoses. This study aims to: (1) expand the detection range of biomarkers through multiple analytical techniques, thereby improving the accuracy of BC diagnosis, and (2) analyze the metabolic pathways of the biomarkers to explore the metabolic mechanisms underlying BC. Urine samples from BC patients and healthy controls were analyzed using two techniques: Ultra-high performance liquid chromatography combined with Quadrupole-Exactive-Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS), and headspace solid-phase microextraction combined with gas chromatography-high resolution mass spectrometry (HS-SPME/GC-HRMS). Data from each platform was analyzed independently using both univariate and multivariate statistical approaches to identify candidate biomarkers. Subsequently, a mid-level data fusion approach was applied to integrate the candidate biomarkers identified by each platform. The fused data were used to construct orthogonal partial least squares discriminant analysis (OPLS-DA) models and random forest (RF) models, which were then compared against models based on individual platform. The fused RF and OPLS-DA models demonstrated enhanced diagnostic accuracy compared to the individual model. Integrating GC-HRMS and UPLC-Q-Exactive Orbitrap-MS achieved the best performance, with an AUC value of 0.967, sensitivity of 86.37 %, and specificity of 89.19 %. Metabolic pathway analysis revealed that 10 metabolic pathways exert an impact on BC. Four pathways—pyruvate metabolism, sulfur metabolism, taurine and hypotaurine metabolism, and tyrosine metabolism—were found to be associated with BC in both metabolomics and volatolomics studies, indicating that these pathways play pivotal roles in BC. This study confirmed the potential of merging multi-platforms to enhance the accuracy of BC diagnosis, offering new avenues for understanding the metabolic mechanisms of BC.
研究领域:
医学
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代谢组学
·
生物信息学
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PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2018
·Vol. 32
·期 10
·e4306
·
IF 1.688
Jie Yang,Zhi Sun,Duolu Li,Fei Duan,Zhuolun Li,Jingli Lu,Yingying Shi,Tanye Xu,Xiaojian Zhang
Shenkang injection is a traditional Chinese formula with good curative effect on chronic renal failure. In this paper, a novel, rapid and sensitive ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole Orbitrap high-resolution accurate mass spectrometry was developed and validated for simultaneous determination of seven bioactive constituents of Shenkang injection in rat plasma and tissues after intravenous administration. Acetonitrile was used as a protein precipitation agent in biological samples disposal with carbamazepine as internal standard. The chromatographic separation was carried out on a C 18 column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). The MS analysis was performed in the full-scan positive and negative ion mode. The lower limits of quantification for the seven analytes in rat plasma and tissues were 0.1–10 ng/mL. The validated method was successfully applied to tissue distribution and pharmacokinetic studies of Shenkang injection after intravenous administration. The results of the tissue distribution study showed that the high concentrations of seven constituents were primarily in the kidney tract. This is the first report of the application of Q-Orbitrap with full-scan mass spectrometry in tissue distribution and pharmacokinetic studies of Shenkang injection.
研究领域:
中药学
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分析化学
·
药理学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Zuo Lihua,Liu Liwei,Yang Yantao,Yang Jie,Chen Min,Zhang Huafeng,Kang Jian,Zhang Xiaojian,Wang Jiabo,Sun Zhi
Prucalopride was widely used for chronic constipation, which is difficult to be adequately relieved by laxatives in adult patients in clinic. Due to the difficulty in metabolite identification, metabolic process of prucalopride had not been investigated in vivo. In this study, an efficient strategy was proposed for comprehensive metabolite profiling of prucalopride after oral administration in rat plasma, urine, and feces samples. This strategy was composed of five steps. First, the samples at multiple time points after oral administration were collected to increase the representativeness of the samples. Second, different sample preparation methods were investigated to obtain superior extraction efficiency. Third, the raw data of test sample and blank sample were acquired using ultra-performance liquid chromatography with Q-Exactive hybrid quadrupole–orbitrap high-resolution accurate mass spectrometry under the positive and negative full-scan/dd MS2 mode. Fourth, combined mass defect filter with background subtraction model in soft of compound discovery, all peaks were constructed to filter potential metabolites after retention time alignment and ion filtration, which could remove large amounts of interference ions. Besides, it can predict potential biotransformation, promoting to understand how to metabolize the drug. This provides multiple possibilities and prevents us conjecturing the potential metabolites blindly. Finally, the verification procedure was implemented through exporting the structure and MS2 spectrum to the analytical tool of Mass Frontier. The proposed strategy significantly improved the targeted detection and identification for metabolites in vivo. A total of 47 metabolites were tentatively characterized in the plasma, urine, and feces samples after oral administration of prucalopride. This study could provide a valuable reference for systematic metabolite profile of drug in vivo.
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高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2017
·
IF 3.255
Pei-le Wang,Zhi Sun,Xiao-jing Lv,Tan-ye Xu,Qing-quan Jia,Xin Liu,Xiao-fang Zhang,Zhen-feng Zhu,Xiao-jian Zhang
Because of the complicated chemical composition of Traditional Chinese Medicines, their chemical profile study has been a great challenge. In the present work, a homologues prediction strategy for rapid screening and identification of C 21 steroids in Xiao-ai-ping injection was developed by using an ultra high performance liquid chromatography coupled with high resolution hybrid quadrupole-orbitrap mass spectrometry. This strategy was characterized by the design of C 21 steroidal skeleton, substituent group and glycan chain in an orderly way, which could quickly and efficiently screen the interested precursor ions. As a result, a total of 95C 21 steroids including 47 potential new ones were identified or tentatively identified, which greatly expanded our knowledge of C 21 steroids in Xiao-ai-ping injection. The results indicated that the homologues prediction strategy not only provided an efficient technique to screen and identify target constituents, but also offered a new perspective for discovery new components in Traditional Chinese Medicines.
研究领域:
药理学
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分析化学
·
传统医学
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PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Xinyi Jiao,Rongrong Li,Simon Sani Ocholi,Haitao Wang,Tongcan Cui,Biying Chen,Liming Wang,Zhifei Fu,Erwei Liu,Fengchao Wang,Lifeng Han
Huanglian (HL) is a member of the Ranunculaceae family, including Coptis chinensis Franch., Coptis deltoidea C. Y. Cheng et Hsiao, or Coptis teeta Wall. The dried rhizomes are highly esteemed herbal medicine in Chinese pharmacopeia. However, the composition of HL is complex, and current identification technologies are insufficient for conducting a comprehensive analysis of HL, leading to major obstacles in quality control. Therefore, an in-depth exploration of the influence of species diversity and geographic provenance on the chemical profile of HL is imperative for its rational application and quality assurance. To comprehensively analyze compounds in HL samples from diverse geographical regions, this study employed an integrated approach combining offline two-dimensional ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry (2D-LC-MS/MS) with online 2D-LC-MS/MS. This dual-platform strategy enabled detailed characterization of complex compound profiles. Additionally, the retention time prediction (RT-Ensemble Pred) models were utilized to predict and identify the retention times of unknown compounds, which particularly facilitated the differentiation of isomers. The comprehensive research resulted in the identification of 150 chemical constituents in HL, including 72 isomers. Furthermore, the compounds were analyzed and categorized according to mathematical classification models, allowing for distinction between various geographical origins. Based on unexposed data, the model demonstrated robust predictive capability, enabling the selection of 20 distinctive characteristic compounds with prominent features for use in geographical origin discrimination. Overall, this multidimensional investigation significantly enhanced our understanding of the chemical composition and inherent variability of HL plant resources, providing crucial technical underpinnings and methodological insights for the comprehensive exploitation and utilization of HL in biomedical and pharmaceutical applications.
研究领域:
中药学
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分析化学
·
植物化学
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PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2022
·Vol. 45
·期 23
·4158-4166
·
IF 3.614
Huan Yang,Wei Wang,Li Zeng,Run Liang,Quanwei Xiao,Yan Zhou,Wenlin Wu,Fang Deng
Citrus , a raw material widely used in food and medicine, is susceptible to fungal infection and its metabolites during growth, transportation, and storage. Thus, monitoring the residual levels of various mycotoxins in Citrus traditional Chinese medicines and related products is crucial. This study described a simple, reliable, and sensitive method for simultaneous identification and quantification of 30 mycotoxins in Citrus products. The method is based on modified quick, easy, cheap, effective, rugged, and safe extraction and purification followed by ultra-high-performance liquid chromatography–quadrupole/orbitrap high-resolution mass spectrometry. The limit of detection ranged from 0.10 to 1.50 μg/kg, and the quantification ranged from 0.25 to 5.00 μg/kg. The recoveries at three spiked levels were 64.90–99.72% and the relative standard deviation was less than 12%. The method was applied to 55 Citrus samples. The detection rates of tentoxin and mycophenolic acid were the highest, reaching 22.7% and with concentration ranges of 0.33–1.03 and 0.57–2.09 μg/kg, respectively. All contamination levels were below the maximum residue limits recommended by the European Commission and China. These results could be used to establish guidelines for screening mycotoxins in Citrus products and the limits of acceptable levels.
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高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2021
·
IF 4.759
Keyu Feng,Simiao Wang,Lifeng Han,Yuexin Qian,Huifang Li,Xue Li,Li Jia,Ying Hu,Huimin Wang,Meiyu Liu,Wandi Hu,Dean Guo,Wenzhi Yang
Herbs represent complex chemical systems involving various primary and secondary metabolites that are featured by large spans of acid-base property, polarity, molecular mass, and content, etc. , which thus poses great challenges to characterize the metabolites contained. Here, the combination of multiple-mechanism chromatography coupled with improved data-dependent-MS 2 acquisition (DDA-MS 2 ) is presented as a strategy to support the deep metabolites characterization. Targeting Uncaria sessilifructus , a reputable medicinal herb containing alkaloids and triterpenic acids (TAs) as the main pharmacologically bioactive ingredients, a three-dimensional liquid chromatography (3D-LC) system was established by integrating ion exchange chromatography, hydrophilic interaction chromatography, and reversed-phase chromatography (IEC-HILIC-RPC). The first-dimensional chromatography, configuring a PhenoSphere SCX column eluted by methanol/20 mM ammonium acetate-0.05% formic acid in water, could well fractionate the total extract into two fractions (unretained ingredients and alkaloids). The subsequent HILIC using an XAmide column and RPC by a CSH Phenyl-Hexyl column achieved the sufficient resolution of the total TAs and total alkaloids, respectively. A polarity-switching precursor ions list-including DDA approach by Q-Orbitrap-MS enabled the high-efficiency, coverage-enhanced identification of alkaloids and TAs. This 3D-LC/Q-Orbitrap-MS system was validated as precise (RSD < 5% for intra-day/inter-day precision), Up to 308 components were separated from U. sessilifructus , and 128 thereof (including 85 alkaloids, 29 TAs, and 14 others) were identified or tentatively characterized, exhibiting superiority over the conventional one-dimensional LC/MS. Conclusively, 3D-LC/MS in an off-line mode can facilitate the flexible configuration of multiple chromatography to accomplish the fit-for-purpose characterization of the metabolites from an herbal extract or a biosample.
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高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2019
·Vol. 42
·期 11
·2069-2079
·
IF 2.516
Bo Yang,Yin Ying,Jie Zou,Shuyu Ge,Lihua Zuo
Dan-Huang-Qu-Yu capsule, a Chinese herbal medicine compound preparation, is widely used for chronic pelvic inflammatory disease. In this study, a rapid, selective, and sensitive microwave-assisted extraction ultra-high-performance liquid chromatography-Q Exactive quadrupole-orbitrap high-resolution mass spectrometry method was developed for analyzing its chemical compositions. A total of 85 compounds, including 22 flavonoids, 8 terpenoids, 5 quinones, 5 phthaleolactone, 23 organic acids, and 22 other compounds were identified from Dan-Huang-Qu-Yu capsule. Among them, 35 major compounds were unambiguously detected by comparing them with reference standards and selected as quality control markers, which were simultaneously determined in Dan-Huang-Qu-Yu capsule. The established method was successfully validated and applied for simultaneous determination of 35 bioactive compounds in Dan-Huang-Qu-Yu capsule from ten sample batches. The quantitative data of the analytes were analyzed by principal component analysis for quality assessment of Dan-Huang-Qu-Yu capsule. Six compounds (e.g., astragaloside IV, salvianolic acid B, ellagic acid, chlorogenic acid, N -butylidenephthalide, and luteolin) were screened out and regarded as chemical markers for quality control of Dan-Huang-Qu-Yu capsule. The established method has been proved to be a novel and useful tool for rapid research of Dan-Huang-Qu-Yu capsule. This research will provide reference for the scientific research of traditional Chinese medicines.
研究领域:
药理学
·
分析化学
·
中药研究
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DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2022
·Vol. 45
·期 18
·3459-3479
·
IF 3.614
Huanyu Guan,Pengfei Li,Qian Wang,Fanli Zeng,Jiashuo Wu,Fangqing Zhang,Shanggao Liao,Yue Shi
Shengjiang Xiexin decoction, a traditional Chinese medical formula, has been utilized to alleviate the delayed-onset diarrhea induced by irino tecan. However, the chemical constituents of this formula and the activities of its constituents remain unclear. In this study, ultrahigh-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry was employed to comprehensively analyze the chemical constituents of Shengjiang Xiexin decoction. A total of 270 components, including flavonoids, coumarins, triterpenoids, alkaloids, diarylheptanoids and others, were identified or characterized. Multidrug resistance-associated protein 2 is an efflux transporter responsible for regulating drug absorption. A total of 20 characteristic components from the formula were selected to evaluate their effects on the function of multidrug resistance-associated protein 2 using the vesicular transport assay. Glycyrrhizic acid and glycyrrhetinic acid were identified as potential multidrug resistance-associated protein 2 inhibitors, while 9 flavonoid aglycones increased the uptake of the substrate [ 3 H]-estradiol 17- β -glucuronide in the vesicles. This was the first systematic investigation of the chemical constituents from Shengjiang Xiexin decoction and the effect of its characteristic components on the transporter. The results offered a basis for further exploring the detoxification mechanisms of this formula and its interactions with other drugs.
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高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Tao Ai,Siyu Yao,Yuanyuan Yu,Kai Peng,Ling Jin,Xifen Zhu,Haijun Zhou,Jiahui Huang,Jianteng Sun,Lizhong Zhu
Sulfonamide antibiotics, extensively used in human and veterinary therapy, accumulate in agroecosystem soils through livestock manure and sewage irrigation. However, the interaction between sulfonamides and rice plants remains unclear. This study investigated the transformation behavior and toxicity of sulfamethoxazole (SMX) and its main metabolite, N4-acetyl-sulfamethoxazole (NASMX) in rice. SMX and NASMX were rapidly taken up by roots and translocated acropetally. NASMX showed higher accumulating capacity, with NASMX concentrations up to 20.36 ± 1.98 μg/g (roots) and 5.62 ± 1.17 μg/g (shoots), and with SMX concentrations up to 15.97 ± 2.53 μg/g (roots) and 3.22 ± 0.789 μg/g (shoots). A total of 18 intermediate transformation products of SMX were identified by nontarget screening using Orbitrap-HRMS, revealing pathways such as deamination, hydroxylation, acetylation, formylation, and glycosylation. Notably, NASMX transformed back into SMX in rice, a novel finding. Transcriptomic analysis highlights the involvements of cytochrome P450 (CYP450), acetyltransferase (ACEs) and glycosyltransferases (GTs) in these biotransformation pathways. Moreover, exposure to SMX and NASMX disrupts TCA cycle, amino acid, linoleic acid, nucleotide metabolism, and phenylpropanoid biosynthesis pathways of rice, with NASMX exerting a stronger impact on metabolic networks. These findings elucidate the sulfonamides' metabolism, phytotoxicity mechanisms, and contribute to assessing food safety and human exposure risk amid antibiotic pollution.
研究领域:
环境科学
·
植物生理学
·
药理学
·
分子生物学
·
毒理学
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高影响因子
危险品化学品经营许可证（带存储）