CURRENT DRUG METABOLISM
·
2024
·Vol. 25
·期 10
·754-768
·
IF 2.1
Xiaoyun Liu,Dafang Zhong,Chongzhuang Tang,Xiaofeng Xu,Hong Lan,Xingxing Diao
Background BPI-460372 is an orally available, covalent, irreversible small molecule inhibitor of the transcriptional enhanced associate domain (TEAD) 1/3/4, which is currently in clinical development for the treatment of cancers with Hippo pathway alterations. Objectives This study aimed to determine the cytochrome P450 (CYP) phenotyping, metabolic stability, and in vitro and in vivo metabolic profile of BPI-460372. Methods The CYP phenotyping and metabolic stability were assessed by measuring the depletion of substrate. The metabolic profile in hepatocytes and rat and dog plasma was analyzed using ultra-high-performance liquid chromatography combined with Orbitrap tandem mass spectrometry (UHPLC-Orbitrap-HRMS). Results BPI-460372 was mainly metabolized by CYP2D6, CYP3A4, and CYP1A2. BPI-460372 exhibited low clearance in human, monkey, and rat hepatocytes, while moderate clearance in dog and mouse hepatocytes. A total of 10 metabolites were identified in five species of hepatocytes, and no human-unique metabolite was detected. In rat plasma and dog plasma, the primary metabolites were M407 (BPI-460430) and M423 (BPI-460456), respectively. The two metabolites were quantitatively determined in rat and dog plasma in pharmacokinetic and toxicological studies. The major metabolic site was 2-fluoro-acrylamide, and major metabolic pathways in hepatocytes, and rat and dog plasma involved oxidative defluorination, hydration, glutathione (GSH) conjugation, hydrolysis, cysteine conjugation, and N-acetyl cysteine conjugation. β-lyase pathway contributed to the metabolism of BPI-460372 in rats to a certain degree. Conclusion This study elucidated the metabolism of BPI-460372 and provided a basis for pharmacokinetic and toxicological species selection, human pharmacokinetics prediction, and assessment of clinical co-administration limitations and possible metabolic pathways in humans.
研究领域:
药理学
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药物代谢
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肿瘤学
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生物化学
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临床药理学
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分析化学
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毒理学
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分子生物学
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DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2021
·
IF 4.952
Zheng Zhou,Yu-Ying Zhang,Jing-Xuan Gao,Li-Xin Ma,Xu-Hui Huang,Jie Zheng,Xiu-Ping Dong,Lei Qin
This study investigated the changes in free amino acids (FAAs), 5′-nucleotides, and lipid compositions of Manila clams ( Ruditapes philippinarum ) collected from December 2017 to November 2018. High-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was used to quantify twenty-one FAAs and six 5ʹ-nucleotides. Lipid profiles were explored by ultra-performance liquid chromatography coupled with a Q-Exactive Orbitrap mass spectrometer with an untargeted lipidomic approach. Results showed significant monthly changes of FAAs, 5′-nucleotides, and lipids profiles. Alanine , glutamic acid , glycine, and aspartic acid , which contributed to the sweet and umami flavor, were the most abundant FAAs in Manila clams. Totally 90 glycerides, 76 glycerophospholipids , 21 lyso-glycerophospholipids, and 52 fatty acids were identified in Manila clams. Among these lipids, most of them possessed a high-level of unsaturation degree. The unsaturation degree of lipids in February, March, and April was the highest, showing the best nutritional value of Manila clams.
研究领域:
海洋生物学
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代谢组学
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食品科学
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营养学
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DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
YueTao Liu,XinQi Li,AiPing Li,Ke Li,XueMei Qin
Danggui Buxue Decoction (DBD), a famous traditional Chinese medicine (TCM), is often used to treat anemia in China. However, its underlying therapeutic mechanism is unclear. Through the analysis of body weight, spleen and thymus indexes, peripheral blood routine and pathological section of femur, it was obviously that DBD could significantly improve acetylphenylhydrazine (APH) + cyclophosphamide (CTX) induced anemia mice in the present work. Ultra high performance liquid chromatography coupled with quadrupole – Exactive mass spectrometry (UHPLC Q-Exactive MS) based metabolomics and lipidomics was further utilized to screen out differential spleen metabolites associated with DBD treatment. A total of 26 differential metabolites including 8 polar metabolites and 18 lipids were firstly obtained to relate with anemia mice. 7 polar metabolites and 10 lipids among them were reversed by DBD, which the regulation of pyrimidine metabolism and glycerophospholipid metabolism were mainly associated to the anti-anemia effect of DBD based on MetaboAnalyst analysis. Through random forest analysis (RF), ROC analysis and pearson matrix correlation, three metabolites, cytosine, uracil and PC (o-16:1(9Z)/20:0), were further screened out as the potential pharmacodynamic biomarkers associated with the efficacy of DBD. This study provided a methodological reference for the study of the mechanism of TCM.
研究领域:
药理学
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中医药学
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代谢组学
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脂质组学
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药物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Analytical Methods in Chemistry
·
2022
·
IF 2.594
Mengjie Xue,Yuting Zhao,Ying Cui,Jing Yang,Yuefei Wang,Xin Chai
Qufeng Zhitong capsule (QZC) is a well-known Chinese patent medicine that has been widely applied for the clinical treatment of rheumatoid arthritis and other inflammatory diseases. To date, its material basis is still unclear, which has greatly limited its clinical application. In this study, by taking advantage of ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry, 16 chemical components such as gallic acid, protocatechuic acid, and neochlorogenic acid in QZC were characterized and unambiguously identified based on comparison with the corresponding reference standards. In addition, the correlation between the focused components and their corresponding raw herbs from QZC prescription was investigated. For the first time, the relationship between the components mentioned above and their anti-inflammatory activity was explored via network pharmacology analysis, and a visualized network of “medicinal materials-QZC-compounds-targets-pathways” was established. Based on the brief prediction results of network pharmacological analysis, ultra-performance liquid chromatography coupled with photodiode array detector method was validated in terms of linearity, limit of detection, limit of quantification, precision, repeatability, stability, and recovery test and was successfully employed to determine 16 compounds in 28 batches of QZCs, which confirmed the feasibility and reliability of the established method for the quantitative analysis of 16 compounds in QZC. Considering the content and bioactivity of the tested components, four compounds were recommended as candidate indicators for quality evaluation ultimately. The potential value of this study could not only support a quality evaluation of QZC but also provide a theoretical basis for further in-depth research of QZC in clinical research.
研究领域:
药理学
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分析化学
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中药学
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网络药理学
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质量控制
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2022
·Vol. 415
·期 3
·493-507
·
IF 4.478
Li Zhuoya,Huang Xinyi,Wang Xuan,Ren Jianwei,Xu Buyi,Luo Chunying,Wang Yanjun,Wang Lian,Harada Kouji H.,Zou Xiaoli
A rapid and sensitive high-performance liquid chromatography–high-resolution orbitrap mass spectrometry method was developed for the simultaneous screening of 354 organic poisons and metabolites in blood and urine, including drugs, medications, pesticides, rodenticides, veterinary drugs, alkaloids, and mycotoxins with a multi-toxicant chromatography-mass spectrometry information library. The method and library showed good prospects in clinical poisoning screening and forensic toxicological identification. Blood and urine samples were extracted successively with ethyl acetate in acidic and alkaline conditions; then, the extract was blown to nearly dry by nitrogen gas and redissolved with methanol-aqueous solution (v:v, 50:50), and the dissolved solution was analyzed by LC-MS/MS after filtering. Precursor ions’ m / z was set for identification, retention time, fragment ions, and isotopic pattern which were used for confirmation. No interference peaks were found in the blank samples, showing good specificity. The LODs of toxicants in urine and blood were 1.00×10 −3 –50.0 ng/mL and 2.07×10 −3 –50.0 ng/mL, respectively, while the LOQs were 3.30×10 −3 –1.67×10 2 ng/mL and 6.91×10 −3 –1.67×10 2 ng/mL. The intra-day precision and inter-day precision of urine samples were 2.31–9.13% and 4.75–12.3%, respectively, which were 1.92–10.8% and 2.01–12.1% in blood samples. The established method was applied to analyze 9 cases of clinical poisoning patients, and bromadiolone, carbofuran, and amanitins were detected, respectively. A total of 382 biospecimens from drug abusers were analyzed with the proposed method, which indicated that some drugs were detected in 62 cases, mainly including methamphetamine, heroin, and MDMA. The results were consistent with the information from traditional liquid chromatography-triple quadrupole mass spectrometry. Graphical abstract
研究领域:
临床医学
·
法医学
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Yueying Jin,Shengyu Cheng,Ruobai Liu,Chenglong Yu,Lingli Zhang,Xi-Ling Li,Guanghai Yan,Mingyu Zheng,Jun Zhe Min
Lurong Dabu decoction (LRDBD) is an effective traditional Chinese Korean ethnic medicine prescription composed of eight herbs, which is used for treating asthma. However, its material basis has not been studied yet. Herein, the use of a new and highly sensitive UHPLC–Q Exactive Orbitrap–HRMS technique is proposed for the high-resolution and accurate identification of the material basis of LRDBD. We identified 122 compounds belonging to different groups in LRDBD. Among these, 23 ingredients produced by decoction were identified and compared with 8 single herb compounds. Moreover, 39 other significantly different compounds were identified. Additionally, 29 absorbed prototype components and 35 metabolites were identified in rat plasma. Half of the prototype components were originated from antler velvet, it has corroborated the compatibility theory of Sasang medicine. To the best of our knowledge, the material basis of LRDBD was characterized for the first time. Our findings provide basic data and a method for further discovering potential drug targets and revealing the action mechanism of LRDBD in asthma treatment.
研究领域:
药理学
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分析化学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2025
·
IF 4
Tao Yang,Xinling Li,Jianhua Tan,Wenyao Liang,Xianzhi Peng
Sulfate and sulfonate compounds are extensively used as anionic surfactants in personal care products (PCPs), which might pose adverse potential to human health. However, available research mostly identified certain subsets of sulfated and sulfonated surfactants based on target analysis. In this study, we developed a comprehensive nontarget strategy for identification of sulfated and sulfonated surfactants in PCPs using UHPLC HRMS supplemented by an in-lab R script based on characteristic fragment ions and sulfur isotope patterns. A total of 20 sulfate and 12 sulfonate surfactants of confidence level 3 and above were identified in the range of alkyl chain length from C12 to C26 with 0–7 ethoxy groups and molecular weights of 200–600 Da in the PCP samples. The sulfates included 4 alkyl sulfates and 16 alkyl ether sulfates. In addition to commonly reported 4 alkyl benzene sulfonates, this study identified eight sulfonate surfactants for the first time, which were 3 alkyl sulfonates, 3 methyl ammonium sulfonates, and 2 bis-sulfonate sulfonates in the PCPs. Interestingly, 22 sulfate and sulfonate compounds were identified in the negatively labeled PCP samples which were not supposed to contain sulfate and sulfonate surfactants. The results demonstrated robustness of the developed nontarget analyzing strategy in identifying and characterizing sulfate and sulfonate surfactants and consequently providing guidance for management and regulation of chemical addition in PCPs to ensure safe use.
研究领域:
环境科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2026
·Vol. 14
·期 7
·e72115
·
IF 5
Bin Li,Ruiyi Fan
Fingered citron ( Citrus medica L. var. sarcodactylis Swingle) is a medicinal and edible citrus fruit cultivated in several major production regions of China. However, comprehensive information on its regional metabolite variation and its chemical differentiation from chayote ( Sechium edule ), a botanically unrelated commodity that may be confused with fingered citron because of partially overlapping Chinese vernacular names, remains limited. In this study, untargeted UPLC‐Q‐Orbitrap MS/MS was used to profile fingered citron samples from Zhejiang (CF1), Sichuan (CF2), Guangdong/Guangxi (CF3), and Yunnan (CF4), together with chayote samples used as a targeted authentication comparator (CFM). A total of 380 metabolites were putatively annotated, including 47 secondary metabolites comprising 23 flavonoids, 8 terpenoids, 8 phenols, 3 coumarins, 3 alkaloids, and 2 steroids. Multivariate analyses and hierarchical clustering identified 65 differential metabolites, including 19 secondary metabolites, that clearly separated the five sample groups within the present dataset. The very high cross‐validated Q 2 values should nevertheless be interpreted cautiously because of the large taxonomic and metabolic distance between C. medica and S. edule and the limited sample size. The interspecific separation was therefore interpreted as an expected chemotaxonomic difference with practical authentication value, rather than as a comparison between biologically equivalent taxa. Phenylalanine metabolism and flavone and flavonol biosynthesis showed the strongest nominal enrichment, although neither remained significant after FDR correction. These results provide a metabolite reference for regional quality discrimination of fingered citron and identify candidate chemical features for its targeted authentication against chayote. Further validation using independent samples, additional production years, and other potential comparator commodities is required before routine application. Untargeted UPLC‐Q‐Orbitrap MS/MS metabolomics was used to profile fingered citron ( Citrus medica ) from four Chinese production regions (CF1–CF4) and chayote ( Sechium edule , CFM). Of 380 putatively annotated metabolites, 65 differential metabolites distinguished the five groups, clearly separating chayote from fingered citron and highlighting regional chemical variation among fingered citron cultivars.
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Peng Gan,Xin Zhang,Yu Wang,Qianru Zhou,Xiaoli Zou
The prevalence of carcinogenic N-nitrosamines formed as byproducts during water treatment was public health of significant concern. The salt-assisted liquid-liquid microextraction (SALLME) combined with gas chromatography-tandem Q-Exactive Orbitrap mass spectrometry, employing programmed temperature vaporization–large volume injection (PTV-LVI) was developed for the determination of sixteen N-nitrosamines. The Plackett-Burman Design and Response Surface Methodology were applied to optimize the PTV-LVI parameters and sample pretreatment procedures. The optimal SALLME conditions were 200 μL dichloromethane as extraction solvent, 30 % (w/v) sodium carbonate concentration, and 40 s extraction time. The optimized PTV-LVI injection volume of 5 μL demonstrated approximately one order of magnitude greater sensitivity compared to conventional 1 μL splitless injection. Under these optimized conditions, the proposed method exhibited linearity correlation coefficients between 0.9947 and 0.9998 for sixteen N-nitrosamines within the range of 0.2–100 μg/L, except for NDMA and NMEA, which showed corresponding correlation coefficients of 0.9937–0.9941 over a linear range of 0.5–100 μg/L. The method detection limits ranged from 1.6 to 4.6 ng/L. The relative recoveries for spiked tap water samples at concentrations of 20 ng/L, 50 ng/L and 100 ng/L ranged from 60.4 % to 113.4 %, with the relative standard deviation below 10 %. The proposed method offered a rapid, environmentally friendly and highly sensitive alternative analytical method for the determination of trace level of N-nitrosamines in drinking water.
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产品关联
DOI
PubMed
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2020
·Vol. 34
·期 19
·e8880
·
IF 2.2
Meilong Lu,Ke Li,Hailang He,Yating Cheng,Peng Yang
Rationale Eomecon chionantha Hance (ECH), a traditional folk herb, is commonly used to treat traumatic injuries based on its analgesic and anti-inflammatory properties. Previous studies have reported that alkaloids are the major bioactive components in ECH. Therefore, identification of alkaloids from ECH contributes to the discovery of its potential active ingredients and quality control in clinic treatments. Methods A four-step screening strategy was performed as follows. (1) Extracting the accurate masses of ions related to different molecules. (2) Screening different types of compounds using their molecular cations, protonated molecules, diagnostic product ions and fragmentation pathways. (3) Comparing the characteristic product ion formulae to obtain the type and number of substituents. (4) Using the biosynthetic pathways of isoquinoline alkaloids to determine the concentration of alkaloids. Results Ultrahigh-performance liquid chromatography–tandem quadrupole Exactive Orbitrap mass spectrometry (UHPLC/Q-Exactive Orbitrap MS) analysis combined with the four-step screening strategy was used to profile the alkaloids in ECH. The structures of 95 alkaloids in ECH were unambiguously identified or reasonably assigned, of which 76 were reported in ECH for the first time. Six types of benzylisoquinoline alkaloids were identified in ECH: six benzyltetrahydroisoquinolines, nine protopines, five N -methyltetrahydroprotoberberines, six protoberberines, eight benzophenanthridines and sixty-one dihydrobenzophenanthridines. Conclusions This comprehensive study identified the alkaloids in ECH, thus providing a practical reference for further research. The UHPLC/Q-Exactive Orbitrap MS method, combined with the four-step screening strategy, which was developed and successfully applied to identify the alkaloids in ECH, may also be applicable for the efficient screening of other herbal medicines.
研究领域:
中药化学
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分析化学
·
药物学
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产品关联
DOI
PubMed
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2020
·Vol. 34
·期 21
·e8893
·
IF 2.2
Yunfeng Chai,Hongping Chen,Chengyin Lu
Rationale Loss of carbon dioxide is an important characteristic fragmentation reaction of deprotonated benzoic acid and its derivatives in electrospray ionization mass spectrometry. However, researchers have rarely noticed or believed that the loss of carbon dioxide in multistage mass spectrometry is a “reversible reaction,” that is, the fragment anion generated by carbon dioxide loss can capture another carbon dioxide to regenerate its precursor ion. Methods The fragmentation of the [M − H] − ions of dicamba (3,6-dichloro-2-methoxybenzoic acid) and benzoic acid was performed with an electrospray ionization hybrid quadrupole-orbitrap mass spectrometer. The structural confirmation of the precursor ions and their product ions was supported by accurate mass (elemental composition) analysis. Pseudo-MS 3 experiments (in-source collision-induced dissociation as MS 2 ) and isotope labelling experiments were used to confirm the addition of carbon dioxide to the product ions in MS 2 . Results In the fragmentation of deprotonated dicamba ( m / z 219), the relative abundance of the precursor ion does not decrease significantly or even increases as the collision energy increases. When the m / z 145 and 175 product ions were isolated in the mass analyzer, the ions 44 m / z units larger ( m / z 189 and 219) were generated spontaneously, indicating the formation of carbon dioxide adduct ions. In the fragmentation of deprotonated [ carboxyl - 13 C]-benzoic acid ( m / z 122), a deprotonated [ carboxyl - 12 C]-benzoic acid ion ( m / z 121) was generated which was derived from 13 CO 2 loss and 12 CO 2 addition. The isotope labelling experiment further supports the formation of CO 2 -attached ions in the fragmentation of deprotonated benzoic acids. Conclusions Under collisional activation, deprotonated dicamba and benzoic acids easily undergo carbon dioxide loss, but the decarboxylated product anions have an appropriate nucleophilicity to carbon dioxide and they can capture a background carbon dioxide molecule remaining in the vacuum system to regenerate the precursor ions. This study provides a new and deeper understanding of the gas-phase chemistry of deprotonated benzoic acid derivatives in mass spectrometry.
研究领域:
分析化学
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质谱学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Ying-Ying Jin,Zi-Qi Shi,Wen-Qi Chang,Lin-Xiu Guo,Jian-Liang Zhou,Jian-Qun Liu,Li-Fang Liu,Gui-Zhong Xin
Recent studies have demonstrated the important role of short-chain fatty acids (SCFAs) in the maintenance of homeostasis of respiratory immunity. However, there is still no report focus on the determination of SCFAs level in bronchoalveolar lavage fluid (BALF), the most common sample used for screening biomarkers of the pulmonary diseases. Herein, an ultra-high-performance liquid chromatography with LTQ-Orbitrap mass spectrometer (UHPLC-LTQ-Orbitrap) oriented 3-nitrophenylhydrazine (3-NPH)-based derivatization method was developed for the quantification of SCFAs in BALF. To achieve accurate quantitation, d4-acetate was used as internal standard to compensate for the matrix effects. Method validation showed a good linearity ( R 2 > 0.9992) with wide concentration range, and the intra-day and inter-day precision for determination of eight SCFAs in BALF samples was ≤ 14.79%. The quantitation accuracy, assessed by relative recoveries, ranged from 90% to 110% for target SCFAs at three concentration levels. Matrix effects ranged from 85% to 115%, and the lower limits of quantification of these targeted SCFAs were varied from 3 to 24 nmol/L. The SCFAs-targeted method was then applied to determine the changed levels in BALF samples from OVA-induced asthma mice and normal mice. In addition, the universality of our developed method was also demonstrated by determining the SCFAs concentrations in feces, serum and lung tissue samples from asthma and normal mice. These results indicate that 3-NPH derivatization based UHPLC-LTQ-Orbitrap provides accurate view of global SCFAs alternation in different samples, giving a support to deduce the origin of SCFAs in lung. The present study is of great importance for understanding the role of SCFAs in modulation of host metabolism and immunity.
研究领域:
分析化学
·
呼吸医学
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免疫学
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质谱技术
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）