{"title":"Simultaneous Quantification of Filgotinib and Its Active Metabolite in Human Plasma Using Liquid Chromatography–Tandem Mass Spectrometry: Validation and Clinical Application","authors":"Takahiro Ito, Manabu Suno, Minae Shintani, Ayaka Iwata, Takao Fujii, Kazuo Matsubara","doi":"10.1002/bmc.70030","DOIUrl":"https://doi.org/10.1002/bmc.70030","url":null,"abstract":"<p>Filgotinib (FLG) is a Janus kinase 1 inhibitor and is metabolized to an active metabolite, GS-829845. There is no report on the method for simultaneous quantification of FLG and GS-829845 in clinical samples. We developed a liquid chromatography–tandem mass spectrometry method for simultaneous determination of FLG and GS-829845 in patient plasma. FLG and GS-829845 were extracted from an aliquot of 50 μL of human plasma by simple deproteinization using methanol. Chromatographic separation was performed using a Shim-pack Scepter C18-120 column with a combined mobile phase of water and methanol containing 0.1% formic acid and gradient elution at a flow rate of 0.2 mL/min. Detection was performed by positive electrospray ionization using a QTRAP 4500 mass spectrometer. The method was validated in the concentration range of 2.5–50 ng/mL for FLG and 250–5000 ng/mL for GS-829845. Intra- and inter-day assay accuracy and precision were within 11.4% and 13.9%, respectively. Recoveries and matrix effects were consistent and reproducible. This developed and fully validated method is simple, rapid, and cost-effective and was used successfully for therapeutic drug monitoring in a patient with rheumatoid arthritis.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmc.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantification of Pectolinarin in Rat Plasma Using UPLC-MS/MS and Its Pharmacokinetic Analysis","authors":"Mengmeng Shao, Runrun Wang, Congcong Wen, Xianqin Wang, Yongxi Jin, Saiya Chen","doi":"10.1002/bmc.70032","DOIUrl":"https://doi.org/10.1002/bmc.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>Pectolinarin is a flavonoid compound known for its wound-healing properties, including anti-inflammatory and antibacterial effects. In this study, we employed UPLC-MS/MS to quantify pectolinarin in rat plasma and investigate its pharmacokinetics. Plasma samples were processed using an acetonitrile precipitation method. Chromatographic separation was performed on a UPLC BEH column with a gradient mobile phase of acetonitrile-water (containing 0.1% formic acid). Detection was carried out using electrospray ionization (ESI) tandem mass spectrometry in multiple reaction monitoring (MRM) mode with positive ionization, targeting transitions of <i>m</i>/<i>z</i> 623.3 → 315.3 for pectolinarin and <i>m</i>/<i>z</i> 370.5 → 125.0 for the IS. The results demonstrated that pectolinarin exhibited acceptable linearity in rat plasma within the concentration range of 1.2 to 2300 ng/mL (<i>r</i> > 0.995). The intraday and interday precision, expressed as relative standard deviation (RSD), was below 9.2%. Accuracy ranged from 97.3% to 108.3%, with average recovery exceeding 94.7%. The matrix effect was between 97.8% and 105.3%. The method was successfully applied to evaluate the pharmacokinetics of pectolinarin in rats following both oral and intravenous administration. The absolute bioavailability of pectolinarin in rats was determined to be 0.28%.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439118","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}
Meng-Yuan Zhang, Yuan-Wei Zhang, Sheng-Nan Yu, Nuo Qiao, Xing-Feng Ni, Qian Liu, Ming-Yu Bai, Qing-Qing Li, Zi-Xuan Wang, Yun Zhou, Ning Ding, Shan-Liang Sun, Xin Xue, Chen-Xiao Shan, Zhi-Hao Shi, Jin Wang, Nian-Guang Li
{"title":"Metabolite Profiling of Danatinib in Mice Using Ultra-High-Performance Liquid Chromatography/Tandem Mass Spectrometry In Vitro and In Vivo","authors":"Meng-Yuan Zhang, Yuan-Wei Zhang, Sheng-Nan Yu, Nuo Qiao, Xing-Feng Ni, Qian Liu, Ming-Yu Bai, Qing-Qing Li, Zi-Xuan Wang, Yun Zhou, Ning Ding, Shan-Liang Sun, Xin Xue, Chen-Xiao Shan, Zhi-Hao Shi, Jin Wang, Nian-Guang Li","doi":"10.1002/bmc.70022","DOIUrl":"https://doi.org/10.1002/bmc.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>Danatinib, a brand-new compound synthesized in our laboratory for the treatment of acute myeloid leukemia (AML), demonstrates remarkable antitumor activity. However, the pharmacokinetic profile of Danatinib in mice was short with its half-life was only 0.476 h. To address this issue and optimize its therapeutic efficacy, this study investigated the metabolic profiles of Danatinib in mice, both in vitro and in vivo, using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS) technology. In the in vitro study, Danatinib was analyzed using mouse liver microsomes, resulting in the identification of eight metabolites. In the in vivo study, Danatinib was administered orally to mice at 20 mg/kg; the samples of plasma, bile, feces, and urine were collected and analyzed, leading to the identification of 34 metabolites. The results showed that those metabolites were formed through various metabolic reactions including hydroxylation, carboxylation, acetylation, hydrogenation, and glucuronidation. This study provides a systematic investigation of the metabolism of Danatinib, offering valuable information for further structural modification to improve its pharmacokinetic profiles.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389314","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}
{"title":"Systematic Investigation of Metabolism and Potential Pharmacological Mechanism of Tanreqing Injection to Human Lower Respiratory Tract Infection Based on UPLC–Q–TOF–MSE and Network Pharmacology","authors":"Huanlu Wang, Xi Mai, Yan Jing, Shuhao Liu","doi":"10.1002/bmc.70024","DOIUrl":"https://doi.org/10.1002/bmc.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>Tanreqing injection (TRQI), a well-known traditional Chinese medicine, has a marked curative effect on lower respiratory tract infections. A strategy using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC–Q–TOF–MS<sup>E</sup>) for rapid identification of metabolites from TRQI was proposed by UNIFI informatics platform combined with multiple data processing techniques. Target prediction was then performed based on the original compounds in vivo, and a network between the active compounds and common targets was established using Cytoscape v3.9.0. As a result, 64 original compounds were characterized in TRQI, and 54 original compounds and 76 metabolites of TRQI were detected in human plasma and urine, two of which (M28 and M45) were novel metabolites. A novel metabolic pathway for lonicerin was identified. The compound-target-pathway network identified 22 target genes and 20 signaling pathways that were linked to these mechanisms. The key mechanism is related to the JAK-STAT signaling pathway and PI3K-Akt signaling pathway. The bioactive ingredients and mechanisms of action of TQRI against lower respiratory tract infections based on original compounds in vivo were explored through network pharmacology and molecular docking. This is the first study in which the mechanism of action of TRQI in humans has been clarified.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389321","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}
Wang Ya-zhu, Wang Xiao-ting, Tian Shu-qing, Gao Hui
{"title":"Analysis of Blood Absorption Components by UPLC-Q-TOF-MS/MS From Anemarrhenae Rhizoma Before and After Salt Processing","authors":"Wang Ya-zhu, Wang Xiao-ting, Tian Shu-qing, Gao Hui","doi":"10.1002/bmc.70025","DOIUrl":"https://doi.org/10.1002/bmc.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>To investigate the material basis for the increased efficacy of Anemarrhenae Rhizoma (AR) after salt processing, this study employed UPLC-Q-TOF-MS/MS technology to analyze metabolites in both AR and salt-processed AR (SAR) extracts, as well as in serum samples treated with these extracts. The results identified 54 chemical components in AR and SAR under both positive and negative ion modes, with 21 prototype components detected in the bloodstream. A comparative analysis of serum absorption levels revealed higher concentrations of neomangiferin, mangiferin, and other chemical constituents in the SAR group than in the AR group. Additionally, 29 differential metabolites were identified, with 12 unique to AR and 17 to SAR. These findings highlight significant alterations in the chemical composition of AR after salt processing and provide a scientific basis for understanding the enhanced efficacy of SAR. This study offers valuable insights for further research into the clinical efficacy of SAR and its applications.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389322","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}
{"title":"Bridging the Gap: Eco-Friendly HPLC Analysis of Metformin and Lobeglitazone Sulfate Despite Polarity and Dosage Differences","authors":"Honey Kevat, Ayushi Prajapati, Kiran Parmar, Bhumika Maheriya, Hardi Joshi, Jigna Vadalia, Kashyap Thummar","doi":"10.1002/bmc.70013","DOIUrl":"https://doi.org/10.1002/bmc.70013","url":null,"abstract":"<div>\u0000 \u0000 <p>A precise and stability-indicating high-performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous estimation of lobeglitazone sulfate (0.5 mg) and metformin hydrochloride (500 mg) in pharmaceutical formulations. This method effectively addresses the analytical challenge posed by the significantly different dosage strengths and contrasting polarities of lobeglitazone (water insoluble) and metformin (water soluble). Utilizing a Phenomenex Strong Cation Exchange (250 mm × 4.6 mm, 10 μm) column, the method employed a mobile phase of ammonium dihydrogen phosphate (pH 3.0) and a premix of methanol and acetonitrile (80:20), delivered at a flow rate of 1.0 mL/min. The PDA detector was set at 251 nm to monitor eluents, and the column temperature was maintained at 30°C for optimal separation. The method was validated as per ICH guidelines, covering specificity, linearity, accuracy, precision, LOD, LOQ, solution stability, and robustness. Forced degradation studies under various stress conditions (acidic, basic, oxidative, photolytic, and thermal) revealed no significant degradation products. The method was also assessed for greenness using a AGREE tool, achieving a score of 0.68, demonstrating its eco-friendly nature. Overall, this method is suitable for the routine analysis of these drugs in pharmaceutical formulations.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389019","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}
{"title":"Separation and Quantitative Estimation of Pharmacopeial Organic Impurities, Process-Related Impurities, and Degradation Products of the Anti-Schizophrenia Drug Clozapine in Pharmaceutical Formulations by Using Stability-Indicating HPLC Method","authors":"Abhishek Sharma, Narayana Reddy Pedavenkatagari, Bhujanga Rao Nagulancha, Narasimha Swamy Lakka","doi":"10.1002/bmc.70021","DOIUrl":"https://doi.org/10.1002/bmc.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>Clozapine is an antipsychotic medication primarily used to treat severe schizophrenia symptoms. This research aimed to develop and validate a reliable, rapid, and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) method for measuring organic impurities in clozapine drug substances and products. The chromatographic separation was achieved using an Agilent Poroshell 120 EC-C<sub>18</sub> column with gradient elution, using mobile phases consisting of acetonitrile, methanol, pH 2.4 phosphate buffer, and ethanol. The method operated at a flow rate of 1.0 mL/min, with a 10-μL injection volume, a column temperature of 35°C, and detection at 257 nm. Validation was performed according to ICH Q2(R2) guidelines and USP <1225> general chapter. The method demonstrated optimal resolution between adjacent peaks, with values greater than 1.5, and provided accurate estimations free from interference. Recovery and regression values ranged from 80.0% to 120.0%, with <i>R</i><sup>2</sup> values exceeding 0.9995. The quantification range spanned from the limit of quantification to 150% of the specification level. The stability-indicating capability of the RP-HPLC method was confirmed through forced degradation studies. This method has been successfully implemented in a quality control laboratory for real-time analysis of clozapine drug substances and products.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380143","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}
{"title":"The Continued Mismeasurement of Plasma Serotonin: A Systematic Review","authors":"Saketh Pillalamarri, George M. Anderson","doi":"10.1002/bmc.70016","DOIUrl":"https://doi.org/10.1002/bmc.70016","url":null,"abstract":"<div>\u0000 \u0000 <p>Studies reporting on the analysis of free plasma (platelet-poor plasma, PPP) serotonin (5-hydroxytryptamine, 5-HT) in plasma obtained from healthy humans have been systematically reviewed. The review covered the period from 2010 to July 2024 and is a follow-up of a similar review published in 2011 which found that nearly all published reported of PPP 5-HT were clearly and markedly erroneously high. This problem has persisted unabated with nearly all retrieved 47 reports from the past 14 years also apparently being erroneously high. Possible causes and consequences of the problem are discussed along with potential approaches to improving the analysis and reporting of plasma 5-HT. Most of the errors appear to arise from pre-analytical problems that occur during the preparation of PPP due to residual platelets and/or due to the release of platelet 5-HT. The large number of fields interested in plasma 5-HT and the disparate publication venues appear to have contributed to a general lack of awareness of the difficulties with analyzing plasma 5-HT. The reporting of erroneous plasma 5-HT values has led to unsupported conclusions about possible alterations in plasma 5-HT and about the role of plasma 5-HT across a wide range of biomedical research areas.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380141","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}
{"title":"Research Progress on the Material Basis of Traditional Chinese Medicines Based on Chemical Biology Methods","authors":"Xinyue Bai, Huimin Lin, Ziqi Yang, Fan He, Jianru Chen, Hua Zhou, Yufeng Huang","doi":"10.1002/bmc.70004","DOIUrl":"https://doi.org/10.1002/bmc.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>The chemical biology method is a cutting-edge technology that utilizes chemical research methods and ideas to study life and biomedicine at the molecular level. Recently, it has gradually been applied to screening chemical markers in traditional Chinese medicines. This article reviews the principles and applications of common chemical biology methods, including cell membrane chromatography, affinity ultrafiltration, magnetic bead enrichment, capillary electrophoresis, molecular exclusion chromatography, immobilized fusion target affinity chromatography, etc., in traditional Chinese medicines research. Applying chemical biology methods to screen chemical markers in traditional Chinese medicines has the advantages of simple and fast operation, strong specificity of results, good reproducibility, and high sensitivity, which can achieve high-throughput screening.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362867","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}
{"title":"Chiral Lead Halide Perovskites in Action: Unlocking Enantiomer Separation Puzzle","authors":"Pallavi Singh, Rudra Mukherjee, Anil Kumar","doi":"10.1002/bmc.6085","DOIUrl":"https://doi.org/10.1002/bmc.6085","url":null,"abstract":"<div>\u0000 \u0000 <p>Effective enantiomer separation is vital in many important sectors like pharmaceuticals, agrochemicals, food safety, and biomedical imaging, yet conventional methods are costly, slow, and chemical intensive. This has sparked interest in exploring novel materials like chiral lead halide perovskite nanocrystals to address these challenges. This newly emerging chiral material combines the superior properties of traditional halide perovskites with the unique attributes of chirality, resulting in distinct optoelectronic behaviors. This perspective provides a discussion on future research opportunities in the usage of these chiral LHP NCs for enantiomeric recognition and separation. LHPs exhibit extraordinary photophysical properties, easier surface functionalization, range of bonding interactions, and high surface area to volume ratio that can be used for detecting enantiomers. To the best of our knowledge, the use of chiral halide perovskites for the chiral discrimination of enantiomers has been scarcely reported, presenting a novel opportunity to explore their potential in enantiomeric recognition and separation.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362803","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}