Biomedical Chromatography最新文献

{"title":"Efficient Quantification of Tacrolimus in Rat Plasma With Ultra-High Performance LC–Q–Orbitrap MS: A Precision Pharmacokinetic Analysis Tool","authors":"Xiao-rong Zhang,&nbsp;Jia Yao,&nbsp;Teng-fei Ma,&nbsp;Hao-yu Chen,&nbsp;Heng-ju Xu,&nbsp;Ying-hui Ye,&nbsp;Li-ying Zhai","doi":"10.1002/bmc.70164","DOIUrl":"https://doi.org/10.1002/bmc.70164","url":null,"abstract":"<div>\u0000 \u0000 <p>The narrow therapeutic index of tacrolimus demands precise dose optimization to maintain therapeutic efficacy while minimizing toxicity, underscoring the necessity for reliable analytical techniques to accurately measure drug concentrations in biological matrices. In this study, we developed an ultrahigh-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry method for quantifying tacrolimus in plasma. This approach employed an Acquity UPLC BEH C₁₈ column, leveraging a gradient elution of methanol (A) and water with 0.1% formic acid (B) to ensure meticulous separation of tacrolimus and the internal standard, ascomycin. Operating in positive ionization mode, the system utilized full MS/dd-MS2 scans, capturing comprehensive data for heightened analytical accuracy and precision. The method demonstrated a broad linear range of 0.5 to 500 μg/L, with a low quantification limit of 0.5 μg/L. Notably, it achieved exceptional reproducibility and accuracy, with relative standard deviations and errors below 6%, complemented by consistent extraction efficiencies for tacrolimus at 84.78% to 97.15%. This study successfully showcases an advanced analytical platform for the meticulous quantification of tacrolimus, seamlessly integrating into pharmacokinetic investigations following a 1.2 mg/kg oral dose in rats. The method's deployment revealed its exceptional suitability for capturing intricate pharmacokinetic profiles, underscoring its value in preclinical drug disposition studies.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573428","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":"LC–MS/MS Assay for Simultaneous Quantification of Dual-Targeting 1,5-Diaryl-1,2,4-Triazole Sulfonamides (WA11–13) in Human Plasma","authors":"Fawzy A. Elbarbry,&nbsp;Bethany Hecker,&nbsp;Michael J. Espiritu,&nbsp;Ahmed E. Elsawi,&nbsp;Wagdy M. Eldehna","doi":"10.1002/bmc.70165","DOIUrl":"https://doi.org/10.1002/bmc.70165","url":null,"abstract":"<div>\u0000 \u0000 <p>We recently designed and synthesized novel dual-targeting anticancer 1,5-diaryl-1,2,4-triazole-tethered sulfonamides. Among them, WA11–13 showed promising carbonic anhydrase and VEGFR-2 inhibitory activity. This study presents a validated, sensitive LC–MS/MS assay for quantifying these compounds in human plasma. Such assay would be very important for future preclinical studies and therapeutic drug monitoring. After protein precipitation with acetonitrile, analytes and the internal standard (carbamazepine) were separated on a Phenomenex Kinetex C18 column using binary gradient elution. The mobile phase was 0.1% formic acid in water and acetonitrile (95:5, v/v) at 0.7 mL/min. Total run time was under 6 min. Detection used an API 3500 triple quadrupole mass spectrometer with electrospray ionization in positive mode. Quantification relied on multiple reaction monitoring for high sensitivity and specificity. The method was fully validated per FDA guidelines, showing acceptable linearity, accuracy, precision, selectivity, and stability. Linearity was observed in the ranges of 2.5–750 ng/mL for WA11, 25–1000 ng/mL for WA12, and 50–1000 ng/mL for WA13. The method was successfully applied to spiked human plasma, supporting its potential for therapeutic drug monitoring. Validation confirms the assay's high sensitivity, accuracy, and precision, making it suitable for future preclinical and clinical investigations of these investigational anticancer agents.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573581","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":"Identification and Characterization of Belumosudil Degradation Impurities Using the LC–MS/MS Method and Its Validation","authors":"Kalyani Koganti,&nbsp;Namburi L. A. Amara Babu,&nbsp;Naga Raju Sattu,&nbsp;Koya Prabhakara Rao","doi":"10.1002/bmc.70161","DOIUrl":"https://doi.org/10.1002/bmc.70161","url":null,"abstract":"<div>\u0000 \u0000 <p>For the treatment of chronic graft-versus-host disease (cGVHD), belumosudil (BSL) used as an important therapeutic agent. The stability study of BSL mainly emphasizes the identification and quantification of degradation products formed under different stress conditions such as hydrolysis (acidic, basic, and neutral), oxidation, photolysis, and thermal degradation according to ICH guidelines. In this study, BSL has demonstrated significant deterioration in acidic and basic hydrolysis as well as oxidative stress conditions, while it remains stable in neutral hydrolysis, photolytic, and thermal stress conditions. An LC–MS/MS method for the detection and quantification of BSL degradation products was developed and validated in accordance with ICH Q2 (R1). By using a 25-min gradient program and an Ascentis Express-F5 column (150 × 4.6 mm, 5 μm), this method effectively separated the analyte from its degradation impurities. Moreover, exposure of BSL to oxidative, basic, and acidic conditions resulted in four different degradation products. The formed degradation compounds were identified by using mass spectral data, and plausible fragmentation patterns were proposed by using mass data. This validated stability-indicating assay method confirms its appropriateness for routine analysis and stability investigations of BSL.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558076","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":"Predicting Quality Markers of Xuefu Zhuyu Wan for Postoperative Cognitive Dysfunction Using Integrated LC–MS Analysis and Network Pharmacology","authors":"Mingxin Guo,&nbsp;Jiaqi Zeng,&nbsp;Sang Xu,&nbsp;Xia Wu,&nbsp;Zhiqiang Hu,&nbsp;Xuping Wang,&nbsp;Liangliang Wang","doi":"10.1002/bmc.70160","DOIUrl":"https://doi.org/10.1002/bmc.70160","url":null,"abstract":"<div>\u0000 \u0000 <p>The study aims to analyze the chemical constituents of Xuefu Zhuyu Wan (XZW) based on LC–MS and explore the mechanism of XZW in treating postoperative cognitive dysfunction (POCD) through network pharmacology and identify its potential quality marker (Q-marker). The chemical components of XZW were analyzed by LC–MS, and the corresponding targets were predicted by SwissTargetPrediction. Then POCD targets were obtained by GeneCards, OMIM, PharmGKB, and TTD database, and the “components-targets” and protein–protein interaction (PPI) maps were drawn by Cytoscape 3.9.1. The visualization of GO and KEGG enrichment analysis was obtained by micro-information. Finally, the content of network pharmacology prediction was preliminarily verified by molecular docking. Eighteen compounds were identified in XZW using LC–MS. SwissTargetPrediction predicted 443 compound targets. Among these, there are 352 common targets between the drug and the disease. Using Cytoscape 3.9.1, the main active components were screened as inophyllum E, liquiritigenin, pyrethrin, albiflorin, isoliquiritigenin, prunasin, meranzin, ligustilide, isoglycyrol, and dibutylphenol. PPI analysis identified the top 10 core proteins as: glyceraldehyde-phosphate dehydrogenase (GAPDH), protein kinase B (AKT1), tumor necrosis factor (TNF), src protein (SRC), epidermal growth factor receptor (EGFR), caspase 3 (CASP3), estrogen receptor (ESR1), prostaglandin peroxidase synthase 2 (PTGS2), matrix metalloenzyme 9 (MMP9), and transcription factor (JUN). KEGG enrichment analysis revealed 166 pathways, including the neuroactive ligand–receptor interaction pathway. Molecular docking shows that the active components have a good affinity with the core targets. It is predicted that liquiritigenin, isoglycyrol, inophyllum, and albiflorin could serve as Q-marker for XZW in the treatment of POCD. The chemical constituents of XZW were obtained by preliminary analysis, and the possible pharmacodynamic substances and their mechanism in treating POCD were discussed. The Q-marker of XZW in treating POCD was predicted, which provided basis for its clinical application and drug development.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525043","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":"Exploring the Compatibility Mechanism of Xiaojianzhong Decoction Intervening in Chronic Atrophic Gastritis Rats Based on Serum Pharmacochemistry and Metabolomics","authors":"Wentian Lu,&nbsp;Junjie Guo,&nbsp;Ruoxin Xiang,&nbsp;Yuetao Liu","doi":"10.1002/bmc.70159","DOIUrl":"https://doi.org/10.1002/bmc.70159","url":null,"abstract":"<div>\u0000 \u0000 <p>Xiaojianzhong decoction (XJZ) is a classical traditional Chinese medicine (TCM) formula for treating chronic atrophic gastritis (CAG), but its compatibility mechanism has not been fully elucidated. Traditional pharmacodynamic evaluation, serum pharmacochemistry, and metabolomics techniques were used to link changes in pharmacodynamic substances to changes in the metabolism. The results of serum pharmacochemical analysis showed that the “Jun-drug” affected the metabolism of 3 components in the “Chen-drug,” the absorption of 3 components, and the metabolism of 14 components in the “Zuo-drug”; the “Chen-drug” affected the absorption of 2 components and the metabolism of 12 components in the “Zuo-drug”; and the “Zuo-drug” affected the absorption of 2 components and the metabolism of 4 components in the “Chen-drug.” The analysis of CAG-related metabolites demonstrated that 11 differential metabolites were significantly regulated by “Jun drug,” and 13 differential metabolites were significantly regulated by “Chen drug” and “Zuo drug.” Molecular docking demonstrated that serum components of high correlation exhibited good binding activity to one or more targets of the differential metabolites. This study was helpful to understand the compatibility mechanism of TCM formulas.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519716","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":"Optimization of Extraction of Yiwei Decoction by Network Pharmacology Combined With Response Surface Design and Bioactivity Evaluation","authors":"Wei Zhu,&nbsp;Zepeng Zhang,&nbsp;Zhiqiang Yan,&nbsp;Lei Zhang","doi":"10.1002/bmc.70154","DOIUrl":"https://doi.org/10.1002/bmc.70154","url":null,"abstract":"<div>\u0000 \u0000 <p>Yiwei Decoction (YWD), a traditional Chinese medicine for nourishing yin and promoting fluid production, is a potential treatment for dry eye disease (DED). Network pharmacology identifies YWD’s active components and mechanisms for treating DED, while high-performance liquid chromatography (HPLC) detects active compounds in water-prepared YWD extracts. A Box–Behnken design with response surface methodology was used to optimize the extraction of these components. Using this method, acteoside (AC), quercetin (QR), and methylophiopogonanone A (MA) were detected as the main contributors to anti-DED, acting on SRC, AKT1, PIK3CA, and STAT3, which may affect the development of DED through lipid metabolism, atherosclerosis, and PI3K-Akt and MAPK pathways. Based on the analytic hierarchy process, taking the phytochemical composition and the proliferation rate of YWD on human corneal epithelial cells (HCECs) as comprehensive indicators, the best extraction parameters were obtained as liquid–solid ratio of 8 mL/g, extraction times of 1.636 times, and decocting time of 54.96 min. Verification based on actual conditions, the standardized score is 0.9417 ± 0.0386, which is very close to the predicted score of 0.9328, with an error of less than 1%. This reliable method aids in optimizing the extraction process of traditional Chinese medicine for specific diseases.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503128","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":"Validated LC-MS/MS Method for Quantifying the Antiparasitic Nitroimidazole DNDI-0690 in Preclinical Target Site PK/PD Studies","authors":"Wietse M. Schouten,&nbsp;Katrien van Bocxlaer,&nbsp;Hilde Rosing,&nbsp;Alwin D. R. Huitema,&nbsp;Jos H. Beijnen,&nbsp;Jadel M. Kratz,&nbsp;Charles E. Mowbray,&nbsp;Thomas P. C. Dorlo","doi":"10.1002/bmc.70158","DOIUrl":"https://doi.org/10.1002/bmc.70158","url":null,"abstract":"<p>Understanding the target site pharmacokinetics (PK) of the nitroimidazole analog DNDI-0690, a potential drug for the neglected parasitic disease leishmaniasis, is important due to the diversity of infected tissue sites and potential drug penetration variability. An ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for quantifying DNDI-0690 in murine biomatrices (plasma, liver, spleen, skin, and skin microdialysate). The method used three protein precipitation sample preparation procedures, tailored for different biomatrices, utilizing a surrogate biomatrix approach. Murine tissues were enzymatically homogenized with a Collagenase A mixture. Chromatographic detection was performed on a C18 column using gradient elution, coupled to a QTRAP6500 quadrupole MS, operating in positive ionization mode. The method demonstrated accurate and precise quantification of all murine biomatrices on the surrogate biomatrix calibration standards, with a high and reproducible total recovery ranging from 75.9% to 94.2% (CV% ≤ 2.5%). Matrix interferences were mitigated with a deuterated internal standard. Stability experiments demonstrated that DNDI-0690 remained stable in all biomatrices under various conditions. This validated UHPLC-MS/MS method was successfully used to quantify DNDI-0690 in a target site murine infection model, demonstrating its suitability for future target site PK studies involving DNDI-0690.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmc.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482368","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":"Stability-Indicating RP-HPLC Method Development and Validation for the Quantification of Ketorolac Tromethamine-Related Impurities in Tablets Solid Oral Dosage Forms","authors":"Prasanna Kumar Lankalapalli,&nbsp;Naveen Maddukuri,&nbsp;Ashok Morsu,&nbsp;Vijaykumar Chollety,&nbsp;Pranitha Sambu,&nbsp;Teja Kamireddy","doi":"10.1002/bmc.70109","DOIUrl":"https://doi.org/10.1002/bmc.70109","url":null,"abstract":"<div>\u0000 \u0000 <p>The present manuscript discusses the development and validation of a gradient reversed-phase HPLC method for determining impurities in Ketorolac Tromethamine tablet dosage formulations. The analytes were separated using an Agilent Zorbax SB C8 column (250 × 4.6 mm, 5.0-μm particle size). The mobile phase consisted of 0.05-M ammonium phosphate buffer at pH 3.0 (mobile phase A) and a mixture of 40% methanol and 60% tetrahydrofuran (mobile phase B). The column temperature was maintained at 40°C, with a flow rate of 1.0 mL/min. UV detection was performed at 254 nm. The method demonstrated high specificity, with a linearity range of 0.201–6.445 μg/mL and achieving a correlation coefficient of &gt; 0.999. The method exhibited high accuracy, exceeding 97%. The developed method was validated according to international ICH guidelines for specificity, linearity, precision, accuracy, and robustness. Stress studies indicated that Ketorolac Tromethamine tablets were sensitive to basic, photolytic, and oxidative stress conditions. The method was deemed suitable for quality control purposes, including impurity determination in Ketorolac Tromethamine tablets and stability-indicating studies.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492966","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":"Elucidating the Therapeutic Mechanisms of Dendrobium loddigesii in Gastric Mucosal Injury: An Integrated Approach Combining Serum Metabolomics and Network Pharmacology","authors":"Qiyuan Yang,&nbsp;Jiani Ren,&nbsp;Yumei Huang,&nbsp;Lina Zhong,&nbsp;Jianbei Teng","doi":"10.1002/bmc.70153","DOIUrl":"https://doi.org/10.1002/bmc.70153","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Dendrobium loddigesii</i> Hook is a traditional Chinese herbal medicine widely used in China. Modern pharmacological studies have shown that Dendrobium has immune regulation, anti-tumor, anti-oxidation, and anti-aging, hypoglycemic effect and is often used in the treatment of chronic gastritis. However, as an important source of Dendrobium, <i>D. loddigesii</i> still lacks research in the mechanism of gastric mucosal injury. The purpose of this study was to explore the potential mechanism of <i>D. loddigesii</i> in the treatment of gastric mucosal injury through animal experiments, serum metabolomics, network pharmacology, and molecular docking. Methods: The model of gastric mucosal injury in rats was established by intragastric administration of pungent Chinese medicine liquid mixed with liquor. The body weight, water intake, and food intake of rats were measured during the experiment. At the end of the experiment, the pH of gastric juice and the contents of albumin ALB, MDA, cAMP, and cGMP in serum were measured. HE staining was used to observe the changes of gastric tissue. Serum samples of rats in each group were collected for metabolomics analysis to find differential metabolites of drug intervention of <i>D. loddigesii</i> and their possible regulatory metabolic pathways. By using network pharmacology and molecular docking methods, the active ingredients, key targets, and potential collaterals of <i>D. loddigesii</i> were elaborated. Finally, the integrated pharmacological studies based on serum metabolomics, network pharmacology, and molecular docking showed that <i>D. loddigesii</i> may achieve the therapeutic effect on gastric mucosal injury by regulating arachidonic acid metabolism, phenylalanine metabolism, retinol metabolism, histidine metabolism, and tryptophan metabolism.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472947","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":"Metabolic Profiling of Canertinib: A Comprehensive Cross-Species Investigation Using Advanced UPLC-MS/MS and LC-Orbitrap-HRMS Techniques","authors":"Weiqi Yuan,&nbsp;Gang Shi,&nbsp;Lantu Gou,&nbsp;Jinliang Yang","doi":"10.1002/bmc.70157","DOIUrl":"https://doi.org/10.1002/bmc.70157","url":null,"abstract":"<div>\u0000 \u0000 <p>Canertinib is an EGFR tyrosine kinase inhibitor intended for the treatment of leukemia and non–small cell lung cancer. This study described a UPLC-MS/MS method for quantitatively assessing the metabolic stability of canertinib in liver microsomes. The developed method showed excellent linearity over the concentration range of 10–1000 nM, which is suitable for in vitro high-throughput screening. Canertinib showed marked species-dependent metabolism, with CL_{in vitro, mic} following the order: human (28.3 μL/min/mg protein) &lt; rat (48.2 μL/min/mg protein) &lt; monkey (77.8 μL/min/mg protein). An LC-Orbitrap-HRMS facilitated structural characterization of the metabolites via accurate mass measurements and MS/MS fragmentation interpretation. Post-acquisition data-mining strategies, specifically high-resolution extracted ion chromatograms and multimass defect filtering, were employed to screen the putative metabolite candidates. Sixteen NADPH-dependent metabolites and one GSH conjugate were structurally characterized. Cross-species comparative analysis revealed notable interspecies variations: metabolites M9 and M17 were identified as human-specific, while M15 and M16 demonstrated monkey-specificity. The metabolic pathways of canertinib included oxidative defluorination, <i>O</i>-dealkylation, oxidative deamination, piperidine ring opening, lactam formation, and GSH conjugation. This work represents the first cross-species metabolic investigation of canertinib, providing critical insights into interspecies metabolic disparities. The elucidated metabolic framework advances mechanistic understanding of the compound's pharmacological activity and toxicity profiles.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 8","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472946","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}