Biomedical Chromatography最新文献_第8页

Safety Assessment of Chlorantraniliprole and Methoxyfenozide in Maize: Residue Analysis, Dietary Risk Evaluation, and Estimation of Residues in Animal-Derived Products 玉米中氯虫腈和甲氧虫酰肼的安全性评价：残留分析、膳食风险评估和动物源性产品残留评估

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-07 DOI: 10.1002/bmc.70091

Yizhi Feng, Xibao Wu, Qixia Sun, Yanli Bian, Lin Liang

{"title":"Safety Assessment of Chlorantraniliprole and Methoxyfenozide in Maize: Residue Analysis, Dietary Risk Evaluation, and Estimation of Residues in Animal-Derived Products","authors":"Yizhi Feng, Xibao Wu, Qixia Sun, Yanli Bian, Lin Liang","doi":"10.1002/bmc.70091","DOIUrl":"https://doi.org/10.1002/bmc.70091","url":null,"abstract":"<div>\u0000 \u0000 <p>Field experiments conducted across 12 experimental plots evaluated the application feasibility of chlorantraniliprole and methoxyfenozide in maize cultivation systems. The recovery rates of two pesticides in maize matrices ranged from 95% to 106%, with relative standard deviations (RSDs) of 1%–7%. Analytical results demonstrated that residual concentrations of both pesticides in maize kernels and fresh maize samples remained below the limit of quantitation (LOQ) of 0.02 mg kg<sup>−1</sup> during both 28-day and 35-day harvest intervals under field conditions. Dietary risk assessments demonstrated distinct exposure profiles: chlorantraniliprole exhibited long-term exposure risks of 0.1%–2.3% across domestic and international models, while methoxyfenozide showed higher quotients (0.9%–17.9%). Comprehensive livestock dietary burden calculations indicated that estimated maximum residue levels (EMRLs) for both compounds in animal-derived products including milk, muscle tissue, liver, kidney, and fat showed significant safety margins. All EMRL values were substantially lower than established maximum residue limits (MRLs) set by major regulatory bodies: the Codex Alimentarius Commission (CAC), United States Environmental Protection Agency (US EPA), Japanese Agricultural Standards (JAS), and European Union (EU) regulations.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-Sensitivity LC-MS/MS Approach for Accurate Quantification of N-Nitroso Duloxetine in Duloxetine Pharmaceutical Formulations 高灵敏度LC-MS/MS法准确定量度洛西汀制剂中n -亚硝基度洛西汀含量

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-05 DOI: 10.1002/bmc.70101

Syam Sundhar Sai Kumar Boppana, Kiran Kumar Chagarlamudi, Rajesh Damarapurapu, Venkata Siva Suryanarayana Gurram, Vinod Kumar Manglige

{"title":"High-Sensitivity LC-MS/MS Approach for Accurate Quantification of N-Nitroso Duloxetine in Duloxetine Pharmaceutical Formulations","authors":"Syam Sundhar Sai Kumar Boppana, Kiran Kumar Chagarlamudi, Rajesh Damarapurapu, Venkata Siva Suryanarayana Gurram, Vinod Kumar Manglige","doi":"10.1002/bmc.70101","DOIUrl":"https://doi.org/10.1002/bmc.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>The high-sensitivity analytical method for the detection of <i>N</i>-nitroso duloxetine, which can be carcinogenic in duloxetine medication products, was successfully developed by applying liquid chromatography–tandem mass spectrometry. Chromatographic separation was achieved by using liquid chromatography–mass spectrometry was carried out by employing an Agilent Zorbax Eclipse Plus C18, 4.6 × 150 mm, 5-μm column. The gradient elution mode was used to operate the mobile phase, which consisted of Phase A, which was a solution of 0.1% ammonia and 0.1% formic acid in water, and Phase B, 100% methanol. This approach overcame duloxetine challenges. Tandem mass spectrometric detection with positive electro spray ionization in MRM mode then found <i>N</i>-nitroso duloxetine. Quality control involves verifying the method for precision, specificity, linearity, accuracy, and robustness, following ICH and USP criteria <1225> to ensure suitability and consistent results. On the other hand, the correlation coefficient (<i>r</i>) was more than 1.000, the mean impurity recovery ranged from 100.5% to 102.4%, and the relative standard deviation (RSD) values (<i>n</i> = 6) ranged from 1.54% to 2.6% over the ranges of LOQ—150%. This work seeks to simplify risk assessment for <i>N</i>-nitroso duloxetine in duloxetine pharmaceutical formulations by providing a fast and reliable quantitative LC-MS/MS analytical method.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the Anticancer Effects of Xianliu Jieduan Fang on Colitis-Associated Colorectal Cancer Through Network Pharmacology and Experimental Validation 鲜柳解端方对结肠炎相关结直肠癌的网络药理学研究及实验验证

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-05 DOI: 10.1002/bmc.70102

Fang-Lan Li, Bei-Bei Wang, Ke-Feng Zeng, Hao-Yang Chen, Xi-Hua Wu, Yun Wang, Hong-Cheng Lin, Wei-Lin Li, Xiang-Dong Zhao

{"title":"Exploring the Anticancer Effects of Xianliu Jieduan Fang on Colitis-Associated Colorectal Cancer Through Network Pharmacology and Experimental Validation","authors":"Fang-Lan Li, Bei-Bei Wang, Ke-Feng Zeng, Hao-Yang Chen, Xi-Hua Wu, Yun Wang, Hong-Cheng Lin, Wei-Lin Li, Xiang-Dong Zhao","doi":"10.1002/bmc.70102","DOIUrl":"https://doi.org/10.1002/bmc.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>This study evaluated the therapeutic effects of Xianliu Jieduan Fang (XLJDF) on colitis-associated colorectal cancer (CAC) and explored its molecular mechanisms through network pharmacology and experimental validation. Using an AOM/DSS-induced CAC mouse model, we evaluated XLJDF's efficacy. Active components were identified by UHPLC-QE-HRMS. Targets were predicted using SwissTargetPrediction and PubChem, while disease genes were obtained from GeneCards, DisGeNET, and TTD. Core targets and pathways were analyzed via Cytoscape and Metascape. Mechanisms were validated through molecular docking and experiments. XLJDF improved colon pathology and identified 68 active compounds, including nine key components like Kaempferol and Luteolin. Network analysis revealed 959 targets with 29 core genes (AKT1, CTNNB1, GSK3B, etc.). KEGG analysis showed XLJDF primarily acts through Wnt signaling, regulating apoptosis and cell migration. Experimental validation confirmed XLJDF inhibits Wnt/β-catenin pathway by preventing GSK3β inactivation. XLJDF exerts anti-CAC effects via a multi-component, multi-target network. Our study identifies key active compounds and demonstrates that XLJDF suppresses the Wnt/β-catenin pathway by preventing GSK3β inactivation, thereby inhibiting β-catenin stabilization.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validated HPLC-UV Detection Method for Cefiderocol Quantification in a Critical Patient Receiving Fetcroja and Treated With Extracorporeal Replacement Therapies 经验证的高效液相色谱-紫外检测法在接受体外替代治疗的重症患者中定量头孢地罗

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-04 DOI: 10.1002/bmc.70104

Carlos Ezquer-Garin, Rafael Ferriols-Lisart, Manuel Alós-Almiñana, J. A. Carbonell, L. Hurtado, L. García-Vargas, G. Aguilar

{"title":"Validated HPLC-UV Detection Method for Cefiderocol Quantification in a Critical Patient Receiving Fetcroja and Treated With Extracorporeal Replacement Therapies","authors":"Carlos Ezquer-Garin, Rafael Ferriols-Lisart, Manuel Alós-Almiñana, J. A. Carbonell, L. Hurtado, L. García-Vargas, G. Aguilar","doi":"10.1002/bmc.70104","DOIUrl":"https://doi.org/10.1002/bmc.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>A simple, rapid, and sensitive HPLC-UV method for cefiderocol quantification in plasma was developed to study the pharmacokinetic profile in a critical patient receiving Fetcroja and treated with a renal replacement therapy. After a quick deproteinization step by an effective precipitation, a chromatographic separation was performed with a C18 column and a mobile phase composed by acetonitrile and phosphate buffer at pH 3.50, delivered by gradient elution at a flow rate of 1.0 mL min<sup>−1</sup>. The UV detector was set at 260 nm. Metronidazole was used as an internal standard. A total run time analysis of 15 min was obtained. The method was validated according to the standard guidelines and applied to study the pharmacokinetics of cefiderocol in a critical patient. Total run time analysis obtained was shorter than previously HPLC reported methods, being useful for therapeutic drug monitoring or pharmacokinetic profile research.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design of Experiments Approach for the Development of a Validated UPLC-Q-ToF/MS Method to Quantitate Soy-Derived Bioactive Peptide Lunasin in Rabbit Plasma: Application to a Pharmacokinetic Study 兔血浆中大豆来源的生物活性肽Lunasin的UPLC-Q-ToF/MS定量方法的实验方法设计：在药代动力学研究中的应用

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-03 DOI: 10.1002/bmc.70098

Gullapalli Kowmudi, Karthika Anoop, Magham Sai Varshini, Krishnaveni Nagappan, Sreenath Konanki, Thaggikuppe Krishnamurthy Praveen

{"title":"Design of Experiments Approach for the Development of a Validated UPLC-Q-ToF/MS Method to Quantitate Soy-Derived Bioactive Peptide Lunasin in Rabbit Plasma: Application to a Pharmacokinetic Study","authors":"Gullapalli Kowmudi, Karthika Anoop, Magham Sai Varshini, Krishnaveni Nagappan, Sreenath Konanki, Thaggikuppe Krishnamurthy Praveen","doi":"10.1002/bmc.70098","DOIUrl":"https://doi.org/10.1002/bmc.70098","url":null,"abstract":"<div>\u0000 \u0000 <p>A novel ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometric (UPLC-Q-ToF/MS) method for quantifying soy-derived bioactive peptide lunasin in rabbit plasma was developed using design of experiments (DoE) methodology. Lunasin and Neuropeptide Y as an internal standard (IS) were separated on a BEH-C18 column (50 mm × 2.1 mm, 1.7 μm particle size) using 0.1% formic acid solution and acetonitrile as mobile phase delivered for 9 min at a constant flow rate of 0.4 mL/min in gradient mode. The Q-ToF mass spectrometer, equipped with electrospray combined ionization (ESCi) interface, was operated in positive ion mode, and the quantifier ions of lunasin and IS were at <i>m</i>/<i>z</i> 838 and <i>m</i>/<i>z</i> 602, respectively. The lower limit of quantification (LLOQ) was 34.6 ng/mL, and the assay was linear over the concentration range 35–10,000 ng/mL. The accuracy was within a range from 86.7% to 88.9% in terms of mean recovery (<i>R</i>), and the intraday and interday precisions in terms of relative standard deviation (RSD) were < 2.65% and < 6.22%, respectively. The method was successfully applied to a pharmacokinetic study involving oral administration of lunasin-rich processed soybeans (6.56 and 19.1 g/kg) to rabbits.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and Validation of RP-HPLC Method for the Detection of N-Nitroso Meglumine in Pharmaceutical Products 药品中n -亚硝基三聚氰胺反相高效液相色谱检测方法的建立与验证

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-02 DOI: 10.1002/bmc.70064

Naga Chandrarao Jayavarapu, Shubhalakashmi Sengupta, Hanimi Reddy Bapatu, Praveen Kumar Subbappa

{"title":"Development and Validation of RP-HPLC Method for the Detection of N-Nitroso Meglumine in Pharmaceutical Products","authors":"Naga Chandrarao Jayavarapu, Shubhalakashmi Sengupta, Hanimi Reddy Bapatu, Praveen Kumar Subbappa","doi":"10.1002/bmc.70064","DOIUrl":"https://doi.org/10.1002/bmc.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Meglumine, a versatile pharmaceutical excipient utilised in the manufacture of numerous pharmaceutical formulations, is an amino sugar containing a secondary amine, which can form a N-nitroso meglumine under nitrosating conditions. These substances are known to be human carcinogens and mutagens. Thus, the development of trustworthy analytical methods has become increasingly essential. This study offers a structural evaluation and development of a reverse phase chromatographic method for the identification and quantification of impurity. The separation was achieved by utilising a Primesep 100, chromatographic column having a mobile phase consisting of water, acetonitrile and formic acid. An HPLC system equipped with photo diode array and refractive index detectors was used. The analytical method was validated in accordance with regulatory standards, demonstrating high specificity with no interference. It exhibited excellent reproducibility, with a % Relative Standard Deviation of 0.56 in system suitability, and a strong linear correlation (0.999) between concentration and response. The method consistently achieved reliable recovery at all spiked levels with a minimum average recovery of 98.0%, maintaining precision at both method concentration and limit of quantification levels, while demonstrating robustness for intended modifications. The successful validation of this method underscores its potential for extensive implementation in pharmaceutical laboratories.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of Chemical and Potential Anti-Heart Failure Components of Yan-Shi-Qiang-Xin Decoction by UHPLC-Q-Orbitrap HRMS Coupled With Molecular Networking hplc - q - orbitrap HRMS结合分子网络分析炎石强心汤化学成分及潜在抗心衰成分

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-01 DOI: 10.1002/bmc.70100

Wen-Chao Chen, Qin-Qin Fang, Yan Qin, Rong-Sheng Li, Qing-Guang Zhang, Wei Liu, Ping Wang, Si-Xing Zhu

{"title":"Analysis of Chemical and Potential Anti-Heart Failure Components of Yan-Shi-Qiang-Xin Decoction by UHPLC-Q-Orbitrap HRMS Coupled With Molecular Networking","authors":"Wen-Chao Chen, Qin-Qin Fang, Yan Qin, Rong-Sheng Li, Qing-Guang Zhang, Wei Liu, Ping Wang, Si-Xing Zhu","doi":"10.1002/bmc.70100","DOIUrl":"https://doi.org/10.1002/bmc.70100","url":null,"abstract":"<div>\u0000 \u0000 <p>Yan-Shi-Qiang-Xin decoction (YSQXD), a traditional Chinese medicine formula, is clinically effective in treating chronic heart failure, yet its bioactive constituents remain unclear. To address this, a sensitive and reliable UHPLC-Q-Exactive Orbitrap HRMS method was established to separate and identify the chemical constituents in YSQXD and its absorbed constituents in rat serum, heart and liver following oral administration of YSQXD. With the optimized conditions, a total of 134 chemical components were tentatively identified, including 41 terpenoids, 34 flavonoids, 19 alkaloids, nine organic acids, eight amino acids, seven coumarins, six nucleotides, two sterols, and eight other compounds, based on retention times, MS/MS spectra, and literature references. Furthermore, 29, 10, 17 constituents were identified in the rat serum, heart and liver, respectively. Finally, the network pharmacology analysis based on absorbable components indicated that polyporenic acid, bavachalcone, albiflorin, biatractylolide, psoralen, angelicin, neobavaisoflavone, dictysine, isotalatizidine, and 26-hydroxyporicoic acid G exhibited high degree values, suggesting their potential as active ingredients for chronic heart failure treatment. These findings provide a comprehensive chemical profile of YSQXD and its absorbed components, offering valuable insights into its pharmacologically active substances.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Method Validation for the Determination of Nicotine and Nicotine Metabolite Levels in Urine, Serum, and Saliva Samples 测定尿液、血清和唾液样本中尼古丁和尼古丁代谢物水平的方法验证

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-01 DOI: 10.1002/bmc.70096

Gülsüm Abuşoğlu, Duygu Eryavuz Onmaz, Ali Ünlü, Fatma Hümeyra Yerlikaya Aydemir, Sedat Abuşoğlu

{"title":"Method Validation for the Determination of Nicotine and Nicotine Metabolite Levels in Urine, Serum, and Saliva Samples","authors":"Gülsüm Abuşoğlu, Duygu Eryavuz Onmaz, Ali Ünlü, Fatma Hümeyra Yerlikaya Aydemir, Sedat Abuşoğlu","doi":"10.1002/bmc.70096","DOIUrl":"https://doi.org/10.1002/bmc.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>Monitoring nicotine and its metabolites in bodily fluids is crucial for assessing tobacco exposure and related toxicity in clinical practice. Due to its high sensitivity for detecting low-level analytes, liquid chromatography–tandem mass spectrometry (LC–MS/MS) was employed to enhance a robust and accurate analytical procedure for quantifying nicotine and its derivatives in serum, urine, and saliva. Comparative analysis was conducted on samples collected from individuals with and without smoking habits. The LC–MS/MS method utilized an API 3200 triple quadrupole instrument paired with a Phenomenex Luna C18 column. Method sensitivity was demonstrated through evaluation of sensitivity parameters, including LOD and LLOQ for each analyte in all matrices. Inter-assay variability and bias values at the LLOQ level were kept below 20%. In serum, the LOD–LLOQ ranges were 0.02–0.05 μg/L for nicotine, 0.32–0.95 μg/L for cotinine, 0.07–0.25 μg/L for 3-OH cotinine, and 0.22–0.69 μg/L for norcotinine. In urine, the respective values were 0.03–0.10, 0.23–0.82, 0.06–0.14, and 0.20–0.55 μg/L, and in saliva, the values were 0.12–1.59, 0.22–2.34, 0.10–0.17, and 0.33–3.01 μg/L. The proposed method is efficient, specific, and adaptable to routine clinical workflows, providing a valuable tool for monitoring tobacco-related exposure.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and Validation of a Rapid and Simple LC-MS/MS Method for Quantification of the Anti-Microtubule, Anti-Cancer Agent ABT-751 in Human and Mouse Plasma and Mouse Tissues 快速、简便的LC-MS/MS定量测定人、小鼠血浆和小鼠组织中抗微管抗癌剂ABT-751的方法的建立与验证

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-05-01 DOI: 10.1002/bmc.70099

Aristeidis Lentzas, Anna Their, Jos H. Beijnen, Mark C. de Gooijer, Olaf van Tellingen

{"title":"Development and Validation of a Rapid and Simple LC-MS/MS Method for Quantification of the Anti-Microtubule, Anti-Cancer Agent ABT-751 in Human and Mouse Plasma and Mouse Tissues","authors":"Aristeidis Lentzas, Anna Their, Jos H. Beijnen, Mark C. de Gooijer, Olaf van Tellingen","doi":"10.1002/bmc.70099","DOIUrl":"https://doi.org/10.1002/bmc.70099","url":null,"abstract":"<div>\u0000 \u0000 <p>A rapid and selective liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantifying ABT-751, an anticancer agent targeting microtubules. Sample preparation involved protein precipitation using acetonitrile and formic acid (100:1, v/v), providing efficient ABT-751 extraction with minimal ion suppression. Buparlisib (BKM-120) served as the internal standard. Chromatographic separation was achieved on a Zorbax Extend C18 column, with gradient elution from 20 to 95% methanol in 0.1% (v/v) formic acid in water, and MS/MS detection was performed in positive ionization mode. This assay was validated for human plasma, mouse plasma, and various mouse tissues, including brain, liver, lung, and kidney homogenates. Calibrants were prepared in each respective blank biological matrix, except for mouse tumor tissue, and curves were fitted by quadratic regression from 5 to 10,000 nM. For mouse tumor tissue we used human plasma as surrogate matrix for calibrants. Precision and accuracy for intra-day and inter-day measurements were within acceptable limits across low, medium, and high concentrations for all matrices. Stability concerns with ABT-751 in mouse plasma and tissue homogenate samples that were stored for more than 8 months were identified and addressed. A pilot pharmacokinetic study in mice demonstrated the applicability of this validated LC-MS/MS method.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification and Molecular Mechanism of COX-2 Inhibitors From Anisodus tanguticus: Ligand Fishing, In Vitro Validation, Molecular Docking, Molecular Dynamics, and ADMET Analysis 唐古山莨菪中COX-2抑制剂的鉴定及分子机制：配体捕捞、体外验证、分子对接、分子动力学和ADMET分析

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-29 DOI: 10.1002/bmc.70092

Rong Su, Yue Wang, Nixia Tan, Honglun Wang, Qi Dong

{"title":"Identification and Molecular Mechanism of COX-2 Inhibitors From Anisodus tanguticus: Ligand Fishing, In Vitro Validation, Molecular Docking, Molecular Dynamics, and ADMET Analysis","authors":"Rong Su, Yue Wang, Nixia Tan, Honglun Wang, Qi Dong","doi":"10.1002/bmc.70092","DOIUrl":"https://doi.org/10.1002/bmc.70092","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Anisodus tanguticus</i> (Maxim.) Pascher has demonstrated remarkable inhibitory effects on cyclooxygenase-2 (COX-2); however, the effective substances and molecular mechanism remain ambiguous. In this study, surface plasmon resonance (SPR) ligand fishing technology coupled with UPLC-Q-TOF-MS analysis were applied to identify two COX-2 binders, atropine and fabiatrin, from <i>A. tanguticus</i> extracts. In vitro assays verified their potent COX-2 inhibitory effects, with IC<sub>50</sub> values of 16.63 and 10.66 mM, respectively. To elucidate the molecular mechanism underlying their inhibitory effects, we conducted molecular docking and molecular dynamics simulations. Interaction analysis revealed that both atropine and fabiatrin exhibit strong binding affinity and structural stability with COX-2. Subsequent ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions indicated that atropine and fabiatrin had favorable pharmacokinetic properties and low toxicity, suggesting their potential as anti-inflammatory agents. Notably, this is the first study to demonstrate the inhibitory effect of fabiatrin on COX-2. Overall, the integrated approach developed here provides an efficient and reliable strategy for identifying bioactive components from complex traditional Chinese medicine (TCM) systems, which may offer a new perspective and scientific basis for the research and development of naturally targeted drugs.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0