DRUG RESISTANCE UPDATES
·
2024
·
IF 15.8
Dajun Gao,Yanting Shen,Lingfan Xu,Yi Sun,Hailiang Hu,Bin Xu,Zhong Wang,Huan Xu
Aims Tumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC). Methods We conducted analyses using LC-MS/MS on clinical prostate cancer tissue before and after hormone therapy. We established tumor xenograft mouse models, primary tumor cells, and human-derived organoids to detect the novel mechanism of NED and to identify potential therapies. Results The hormone therapy-induced upregulation of acetate metabolism was mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2), which increased c-MYC expression for NED induction. Notably, combined treatment with an ACSS2 inhibitor and enzalutamide significantly reduced the xenograft tumor volume. Conclusion Our findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC.
研究领域:
肿瘤学
·
分子生物学
·
癌症代谢
·
前列腺癌
·
激素治疗
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DOI
PubMed
高影响因子
Animals
·
2025
·Vol. 15
·期 7
·950
·
IF 2.7
Feifei Zhao,Changcheng Lin,Yunying Wu,Xinyue Luo,Ning Han,Wenguang Xiong,Zhenling Zeng
Simple SummaryGabapentin is an analogue of the neurotransmitter γ-aminobutyric acid, which is commonly used to treat neuropathic pain and epilepsy. However, studies have shown that early use of gabapentin can significantly reduce cats’ stress and increase their compliance with veterinary examinations. There is currently little research on the pharmacokinetics of gabapentin tablets for oral administration in cats. Consequently, monitoring gabapentin plasma levels provides critical insights into therapeutic adherence and facilitates early identification of toxicity thresholds. In this study, a novel LC-MS/MS assay was established and comprehensively validated to achieve high-throughput quantification of gabapentin in feline plasma resolution within 7 min. Additionally, this study provides further clinical evaluation for the management of sedation and anti-stress in cats.Gabapentin (GBP), a γ-aminobutyric acid analogue used for neuropathic pain and epilepsy, can reduce cat stress and improve veterinary exam compliance. A sensitive LC-MS/MS assay was established and rigorously validated for quantifying GBP in feline plasma. The method employed acetonitrile-mediated protein precipitation to efficiently extract GBP and its internal standard, pregabalin (PGB). Chromatographic separation was achieved within 7 min using a C18 column (2.1 × 50 mm, 1.7 μm) with a gradient mobile phase comprising 0.1% (v/v) formic acid in water and acetonitrile. The pharmacokinetics of 25 mg/kg GBP was studied by single-dose oral and intravenous administration. The results demonstrated that the method exhibited satisfactory precision, accuracy and linearity. The pharmacokinetic results showed that the Tmax, Cmax, T1/2and AUC0–tof GBP in cats after oral administration of 25 mg/kg were (1.83 ± 0.75) h, (13.94 ± 3.75) μg/mL, (5.60 ± 1.79) h and (115.54 ± 27.56) (μg/mL) h, respectively. The results of the study indicated that after intravenous administration of 25 mg/kg GBP, the C0, T1/2and AUC0–twere (58.82 ± 15.34) μg/mL, (3.87 ± 0.64) h and (160.44 ± 32.65) (μg/mL) h, respectively. The oral bioavailability of GBP in cats was (78.71 ± 18.55)%. In this study, a selective and sensitive LC-MS/MS method for the quantification of GBP in cat plasma was developed and validated. This method was successfully employed to assess the pharmacokinetics following the oral and intravenous administration of GBP in cats.
研究领域:
兽医学
·
分析化学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Results in Chemistry
·
2025
·
IF 4.2
Oushan Tang,Shitong Wang,Guanguan Qiu,Majun Zhang,Liping Ling,Yan Zhang,Meiqun Guo,Chunxia Shen,Bin Quan,Hongjie Lang,Qing Shen,Keyun Cheng
This study proposes a method combining the Captiva enhanced matrix removal (EMR)-Lipid solid-phase extraction column with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the qualitative and quantitative analysis of five common oral anticoagulants (OACs) (rivaroxaban, apixaban, edoxaban, dabigatran, and warfarin) in plasma samples. The method, through a simplified sample pretreatment, significantly enhances the recovery rate of OACs (ranging from 88% to 96%), demonstrating superior purification effects compared to traditional solid-phase extraction methods, and effectively removes matrix interference. The method exhibits good linearity over a concentration range of 0.010 to 5.0 × 10 2 ng·mL −1 (r 2 = 0.9514 to 0.9998), with high sensitivity, detection limits of 0.010 to 0.10 ng·mL −1 , and quantification limits of 0.10 to 1.0 ng·mL −1 . The recovery and precision analysis indicate that the method is highly accurate and stable, suitable for the analysis of large batches of plasma samples containing OACs. This method provides an efficient and reliable testing tool for clinical drug monitoring, contributing to the optimization and enhancement of safety in personalized anticoagulation therapy.
研究领域:
临床药理学
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药物代谢
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分析化学
·
个体化医学
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毒理学
·
生物分析
·
抗凝治疗
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Li Liu,Geng-Yu Bao,Shu-Sheng Zhang,Yong Qin,Xiu-Ping Chen,Ming-Dan Wang,Jian-Ping Zhu,Hang Yin,Guo-Qiang Lin,Chen-Guo Feng,Fang Zhang,Yin-Long Guo
The amine submetabolome, including amino acids (AAs) and biogenic amines (BAs), is a class of small molecular compounds exhibiting important physiological activities. Here, a new pyrylium salt named 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate ([d0]-DMMIC) with stable isotope-labeled reagents ([d3]-/[d6]-DMMIC) was designed and synthesized for amino compounds. [d0]-/[d3]-/[d6]-DMMIC-derivatized had a charged tag and formed a set of molecular ions with an increase of 3.02 m/z and the characteristic fragment ions of m/z 204.1:207.1:210.1. When DMMIC coupled with liquid chromatography-mass spectrometry (LC-MS), a systematic methodology evaluation for quantitation proved to have good linearity (R2 between 0.9904 and 0.9998), precision (interday: 2.2–21.9%; intraday: 1.0–19.7%), and accuracy (recovery: 71.8–108.8%) through the test AAs. Finally, the methods based on DMMIC and LC-MS demonstrated the advantaged application by the nontargeted screening of BAs in a common medicinal herb Senecio scandens and an analysis of metabolic differences among the amine submetabolomes between the carcinoma and paracarcinoma tissues of esophageal squamous cell carcinoma (ESCC). A total of 20 BA candidates were discovered in S. scandens as well as the finding of 13 amine metabolites might be the highest-potential differential metabolites in ESCC. The results showed the ability of DMMIC coupled with LC-MS to analyze the amine submetabolome in herbs and clinical tissues.
研究领域:
分析化学
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代谢组学
·
医学
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DOI
高影响因子
JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2021
·Vol. 60
·期 2
·186-193
·
IF 1.618
Liu Ruichen,Liang Huiliang,Li Zhen,Zang Hengchang
Qilong capsule (QLC) is a well-known Traditional Chinese Medicine, and it has a long history for the treatment of ischemic stroke. Its major ingredients are saponins, such as paeoniflorin, amygdalin and calycosin-7-glucoside, contributing to vasodilation function. In this study, a simple, rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method was developed to determine three bioactive ingredients in rat plasma after oral administration of QLC. A simple acetonitrile precipitation method was introduced during the sample preparation. Chromatographic separation was performed on a Shiseido CAPCELL PAC MGIII-C18 column using a gradient elution with acetonitrile and water (0.1% formic acid) as a mobile phase, and the chromatographic separation was 5 min. The methodological evaluation showed that this method had a high sensitivity (the lower limit of quantification was 1 ng/mL for calycosin-7-glucoside, 5 ng/mL for paeoniflorin, 5 ng/mL for amygdalin), satisfactory accuracy (relative error ≤ ±15%) and precision (relative standard deviation ≤15%). Then, the analytical method was applied to the pharmacokinetic study in rats following oral administration of the extracts in QLC. Meanwhile, the pharmacokinetic parameters of complex system in QLC were analyzed and the potential interaction between ingredients was explored. The present quantification method and pharmacokinetic study will provide a meaningful reference for the formulas research of QLC in the treatment of ischemic stroke.HighlightA simple, rapid and sensitive HPLC–MS/MS analytical method was developed for the simultaneous determination of three ingredients in rat plasma after oral administration of QLC.A simple acetonitrile precipitation method was introduced to extract three biomedical ingredients during the plasma sample preparation.The pharmacokinetic results revealed the pharmacological active substances, identified internal variation rules and provided a meaningful reference for the formulas research of QLC in the treatment of ischemic stroke.
研究领域:
中药学
·
药理学
·
分析化学
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DOI
PubMed
高影响因子
Food Analytical Methods
·
2024
·
IF 2.6
Pan Xingyu,Chen Jinzi,Guo Tao,Kuang Fengjiao,Kang Zonghua,Luo Jianguang
Betel nut (Areca nut, AN) products are extensively consumed across East and South Asian countries, with Binglang being the predominant chewable AN product in China. Given the increased risk of carcinogenicity associated with alkaloid nitrogen oxides compared to the primary alkaloids in AN, this study aimed to establish a precise and sensitive method for quantitative analysis of the arecoline N-oxide (ACNO) and arecaidine N-oxide (ADNO) at three different processing stages of Binglang using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The developed method underwent comprehensive validation, evaluating key analytical parameters including selectivity, linearity, sensitivity, accuracy, precision, and stability. Notably, the method demonstrated excellent sensitivity, with the limits of detection (LOD) ranging from 0.029 to 0.135 ng/mL, while the limits of quantification (LOQ) ranging from 0.095 to 0.450 ng/mL. Subsequently, the established analytical technique was applied to analyze 15 Binglang samples at three different processing stages, providing the first evidence of the content and variability of alkaloid nitrogen oxides throughout these stages. ACNO and ADNO were detected in all samples, and their total contents ranged from 4.31 to 32.82 μg/g. The changes observed across different processing stages indicated that the roasting process at 80 ℃ resulted in the promotion of alkaloid nitrogen oxides. This analytical approach constitutes a valuable tool for the quality control and risk assessment of Binglang and can be extended to other AN products, thereby assisting in addressing health concerns associated with these products.
研究领域:
药理学
·
分析化学
·
食品安全
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhao Huan,Hu Xueli,Guan Shenghong,Cai Jinhong,Li Xiaohan,Fang Jiaxi,Lin Bo,Zhu Wei,Tian Jingkui,Jin Juan,He Qiang,Zhang Xiaoyong
Introduction: Some herbal ingredients can reshape the composition of the gut microbiome as well as its metabolites. At the same time, the gut microbiota can also affect drug metabolism. A large number of studies have reported that saponins are biotransformed under the action of intestinal microorganisms to improve drug efficacy and bioavailability. Capilliposide A is a triterpenoid saponin, which is derived from Lysimachia capillipes Hemsl. CPS-A has anti-inflammatory pharmacological activity, but the substance basis in vivo is unknown at present, so studies on the interaction between intestinal microorganisms and CPS-A may clarify the pharmacodynamic substance basis of CPS-A.Methods: This study established a colitis mouse model, collected sterile feces from normal mice and colitis mice, and incubated CPS-A with two different intestinal flora in vitro. Based on LC-MS, the metabolic process of CPS-A mediated by intestinal microbes and the intervention effect of CPS-A on intestinal microbiome derived metabolites were studied.Results: The results of experiments indicate that intestinal microorganisms can mediate the biotransformation of CPS-A and metabolize it into corresponding deglycosylation products, thereby promoting its drug effect. Not only that, CPS-A can also promote metabolites such as Deoxycholic acid, Histamine, 3-Hydroxytridecanoic acid, and Indole-3-acetic acid in the intestinal microbiota of mice with colitis. This may result in anti-colitis effects. CPS-A mainly involved in metabolic pathways such as azathioprine and mercaptopurine, which may also have beneficial or adverse effects.Discussion: This study on the interaction between CPS-A and microbiota provides a new idea for the study of traditional Chinese medicine with poor oral bioavailability. The regulatory effect of CPS-A on the metabolites of intestinal flora in colitis mice was also found. It laid a foundation for exploring the mechanism of action of saponins on colitis mice.
研究领域:
药理学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2026
·
IF 5.2
Benkai Qin,Huina Zhang,Hangyu Zhao,Yuchen Su,Yifu Kong,Shengshuo Zhang,Luwei Wang,Yonghua Yu,Jie Gu,Tingting Lou
Perospirone hydrochloride hydrate is an atypical antipsychotic widely used in the management of schizophrenia. Reliable quantification of its plasma concentrations remains essential for pharmacokinetic characterization and dose optimization. A rapid, specific, and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and fully validated for the quantification of perospirone in human EDTA–K2 plasma using perospirone-d8 as the internal standard (IS). Chromatographic separation was achieved on a Kinetex C18 analytical column (100 Å, 50 mm × 2.1 mm, 5 μm, 100 Å). The mobile phase consisted of an aqueous solution of 0.1% formic acid and 1 mM ammonium formate (MPA) and a solution of 95% acetonitrile containing 0.1% formic acid and 1 mM ammonium formate (MPB), delivered at a flow rate of 0.300 mL/min. The injection volume was 10 μL. Mass spectrometric detection was performed using electrospray ionization in positive-ion mode with multiple reaction monitoring (MRM). The method exhibited linearity over a concentration range of 0.0200–12.0 ng/mL. The validated method was successfully applied to fasting and postprandial pharmacokinetic studies following oral administration of perospirone hydrochloride tablets. The method demonstrates strong performance characteristics and practical utility, supporting its application in pharmacokinetic investigations, bioequivalence assessment, and clinical drug monitoring.
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DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Hui Zhang,Mengjia Xu,Felix Wambua Muema,Jun Ding,Mingquan Guo
Chrysanthemum indicum L. has traditionally been utilized as one of the main ingredients in many functional foods or tea for lipid-lowing by advantages of abundant bioactive components and lower side effects. However, the specific compounds responsible for these beneficial lipid-lowering properties remain unrevealed. In this study, lipase-immobilized hollow fibers were first developed to screen out potential lipase ligands by integrating ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF-MS/MS) with a molecular networking approach, in which the incorporation of glutaraldehyde as crosslinker achieved a 2.24-fold increase in enzyme loading capacity. The immobilized lipase retained over 50% relative viability after 6 enzymatic cycles or 10 h of storage (4 °C). A total of 30 potential ligands were successfully screened out and identified. Among them, the inhibitory activities and the mechanism of action of three representative candidate ligands (Ethyl chlorogenate, Luteolin 7- O -glucuronide and Ethyl caffeate) were further investigated through in vitro enzyme activity assays and molecular docking analysis. Overall, the current study proposed a promising strategy for the rapid discovery and identification of bioactive compounds against obesity from complex natural extracts in natural foods.
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DOI
高影响因子
JOURNAL OF MASS SPECTROMETRY
·
2026
·Vol. 61
·期 5
·e70057
·
IF 2.1
Daomiao Huang,Hong Chen,Hai Zhang,Xin Dong
In assisted reproductive technology (ART), controlled ovarian hyperstimulation (COS) plays an important role in guiding treatment progress and determining success. Many ovulation-inducing agents are used in this process, including human menopausal gonadotropin (HMG), recombinant follicle-stimulating hormone (r-FSH), recombinant luteinizing hormone (r-hLH), urinary human chorionic gonadotropin (u-hCG), and recombinant human chorionic gonadotropin (r-hCG). HMG, which comes from the urine of postmenopausal women, mainly contains FSH, LH, and hCG. While bioactivity-based potency units and immunoassay-based ELISA methods remain the gold standard for quantifying protein therapeutics, LC–MS/MS is emerging as a game-changing technology. Its unique strengths are exceptional specificity and absolute quantification capabilities, independence from specialized reagents, powerful multiplexing potential, and ability to provide structural insights, establishing it as an essential tool for both orthogonal verification and cutting-edge research in the field. This study used reverse-phase liquid chromatography with mass spectrometry (RP-LC–MS/MS) and a label-free quantitative proteomics method to analyze imported r-hFSH, r-hLH, r-hCG (Gonal-F, Luveris, and Ovidrel), three domestic HMG products (Le Baode, Man Fuxin, and Xin Yunle), and u-hCG (Li Zhu). The results showed that the purity of the main component in imported gonadotropin drugs was higher than 98.55%. On the other hand, the main element of domestic u-HMG is FSH, with small amounts of hCG and very little LH. These results reveal significant differences in the composition of imported and domestic gonadotropin products, underscoring the need to further evaluate their biological activity and clinical effectiveness. This study provides important insights into drug selection for ART, with practical value for improving the quality of HMG drugs and making better use of them in clinical settings.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
·
2026
·
IF 2.1
Zhenhua Zhang,Bingchen Ge,Yanyu Wang,Changrui Long,Huixing Wu,Hui Chen,Shijian Xiang,Benjie Zhou
Objective To develop a novel approach for quantitative analysis of three pharmaceutical agents commonly employed in the treatment of hematological disorders (venetoclax, busulfan, and voriconazole) by liquid chromatography tandem mass spectrometry (LC-MS/MS). Methods The internal standards were venetoclax-d8 (venetoclax), busulfan-d8 (busulfan), and posaconazole (voriconazole), which were separated on a Phenomenex Kinetex® C 18 (2.1 × 50 mm, 2.6 μm) column, and the multiple reaction monitoring was carried out in the positive ion mode of the SCIEX Triple Quad™ 5500. Protein precipitation pretreatment was performed using acetonitrile, with solvent A (2 mmol/L ammonium acetate dissolved in water containing 0.1% formic acid) and solvent B (acetonitrile solution containing 0.1% formic acid) as mobile phases. The flow rate was 0.8 mL/min, and the injection volume was 5 μL. Results The method was validated with regards to selectivity, lower limit of quantification, linearity, precision and accuracy, matrix effect and extraction recovery, dilution integrity, and stability. The runtime of each plasma sample was 3.1 min. The concentration ranges of the calibration curves were 50–10,000 ng/mL for venetoclax and voriconazole, and 15–3000 ng/mL for busulfan, with all the three correlation coefficients greater than 0.999. There were significant drug–drug interactions with venetocalx and voriconazole, and the incidence of adverse reactions was related to the venetoclax exposure in vivo. Concentrations of busulfan and voriconazole showed substantial interindividual variability. Conclusion This study develops, with validation, a novel LC-MS/MS method for simultaneous determination of venetoclax, busulfan, and voriconazole, which is suitable for application to therapeutic drug monitoring in patients with acute myeloid leukemia.
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DOI
PubMed
高影响因子
Biosensors-Basel
·
2026
·Vol. 16
·期 6
·311
·
IF 6.2
Xiqiong Mu,Yaqin Dong,Ling Jin,Tiantian Zhu
This study compares the performance of novel fluorescent nanobiosensors and liquid chromatography–mass spectrometry (LC-MS) for detecting organophosphorus pesticide residues inAngelica sinensis. Key parameters such as recovery rate and relative standard deviation (RSD) were evaluated to identify a preferable detection method. The results show that the fluorescent nanobiosensor offers superior sensitivity, whereas LC-MS excels in accuracy and quantitative analysis. For phoxim, the GQDs@GSH sensor achieved an LOD of 0.075 μmol·L−1, with recoveries of 97.65–100.62% (RSD < 3.35%). For glyphosate, the PDOA/Cu2+sensor achieved an LOD of 1.8 nmol·L−1, and the AgNCs sensor achieved an LOD of 21 nmol·L−1, with recoveries of 91.30–105.34% (RSD < 3.35%). The originality of this work is threefold and does not claim de novo synthesis of unknown materials: (i) it is the first validation of three existing fluorescent nanosensors (GQDs@GSH, PDOA/Cu2+, and AgNCs) specifically for organophosphorus pesticide detection in the complex medicinal plant matrixAngelica sinensis; (ii) it provides the first systematic comparison of these nanosensors against the pharmacopeia-standard LC-MS method in this matrix, delineating their complementary advantages; (iii) it is the first assessment of their phytotoxicity inAngelica sinensisseedlings, demonstrating biocompatibility and potential for in planta imaging.
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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）