Biomedical Chromatography最新文献_第7页

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

Determination of 59 Psychotropic Drugs, Including Antipsychotics, Antidepressants, Antiepileptics, Anti-Alcohol Abuse Drugs, Anti-ADHD Drugs, and Their Metabolites in Urine Using LC–MS/MS for Medication Compliance Monitoring 用LC-MS /MS监测尿中59种精神药物（包括抗精神病药、抗抑郁药、抗癫痫药、抗酒精滥用药、抗adhd药）及其代谢物的用药依从性

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-29 DOI: 10.1002/bmc.70074

Jeong Eun Kim, Seon Yeong Kim, Jae Chul Cheong, Jin Young Kim

{"title":"Determination of 59 Psychotropic Drugs, Including Antipsychotics, Antidepressants, Antiepileptics, Anti-Alcohol Abuse Drugs, Anti-ADHD Drugs, and Their Metabolites in Urine Using LC–MS/MS for Medication Compliance Monitoring","authors":"Jeong Eun Kim, Seon Yeong Kim, Jae Chul Cheong, Jin Young Kim","doi":"10.1002/bmc.70074","DOIUrl":"https://doi.org/10.1002/bmc.70074","url":null,"abstract":"<div>\u0000 \u0000 <p>Increasing social concern regarding individuals with mental health disorders in the criminal justice system has underscored the need for effective strategies to reduce recidivism. Medication compliance monitoring is a critical approach that ensures adherence to prescribed treatments, facilitating the reintegration of these individuals into society. This study focuses on the development and validation of a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for detecting 59 psychotropic drugs and their metabolites in urine, addressing a significant gap in existing monitoring techniques. Utilizing a dilute-and-shoot approach for urine sample preparation, we established a robust analytical method that demonstrated high sensitivity and precision, with limits of detection ranging from 0.07 to 1.5 ng/mL and correlation coefficients consistently above 0.997. The method was validated through various parameters, including selectivity, stability, and accuracy, ensuring reliable performance in forensic applications. Analysis of urine samples from 248 individuals on probation with mental health conditions confirmed the practicality of the method, identifying 53 psychotropic substances. The LC–MS/MS method was successfully applied for medication compliance monitoring of mentally disordered probationers. Therefore, this analytical method could provide clear evidence for preventing the recurrence of mentally disordered crimes.</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":"143889178","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

Comparative Study of Pharmacokinetics and Renal Exposure of Salvianolic Acid B and Its Metabolite Danshensu in Normal and Renal Fibrosis Mice 丹酚酸B及其代谢物丹参素在正常和肾纤维化小鼠体内的药动学和肾暴露比较研究

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-26 DOI: 10.1002/bmc.70094

Pinglan Lin, Fengling Li, Bin Zou, Jing Zhao, Guochao Song, Fengyi Weng, Chen Wang, Jingyi Jin, Furong Qiu

{"title":"Comparative Study of Pharmacokinetics and Renal Exposure of Salvianolic Acid B and Its Metabolite Danshensu in Normal and Renal Fibrosis Mice","authors":"Pinglan Lin, Fengling Li, Bin Zou, Jing Zhao, Guochao Song, Fengyi Weng, Chen Wang, Jingyi Jin, Furong Qiu","doi":"10.1002/bmc.70094","DOIUrl":"https://doi.org/10.1002/bmc.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Salvianolic acid B (SAB), a water-soluble compound in <i>Salvia miltiorrhiza</i> (Danshen), has been widely used in the treatment of renal fibrosis. This study aimed to investigate the pharmacokinetics of SAB and its active metabolite danshensu (DSS) after intraperitoneal injection of <i>Salvia miltiorrhiza</i> depside salt for injection (SDSI) or SAB in normal and unilateral ureteric obstruction (UUO) mice. An LC-MS/MS method was developed to simultaneously determine the SAB and DSS in biological samples. The validation results showed that the linearity, accuracy and precision, matrix effects and recovery, and stability satisfied the FDA bioanalysis guidelines. Pharmacokinetic study showed that plasma and renal exposure of SAB in mice administered SAB were higher than that in mice administered SDSI in the sham group, while those of DSS were lower. Compared with the sham group, the AUC<sub><i>0-t</i></sub> of SAB in obstructed kidneys (OKs) and non-obstructed kidneys (NOKs) of the UUO group decreased by 71.14% and 54.63%, respectively. The AUC<sub><i>0-t</i></sub> of DSS in the OKs and NOKs of the UUO group increased by 60.8% and 177.79%, respectively, compared with the sham group. Developed method was successfully applied to the bioanalysis of SAB and DSS. Our study provides pharmacokinetic support for the rational clinical application of SAB.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875588","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

Investigations Into the Urinary Metabolite Elimination Profile of the Selective Androgen Receptor Modulator S-23 in Studies Mimicking Contaminated Product Ingestion for Doping Control Purposes 选择性雄激素受体调节剂S-23在模拟兴奋剂控制污染产品摄入研究中的尿代谢物消除谱研究

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-25 DOI: 10.1002/bmc.70090

Hana Alhalabi, Linus Korsmeier, Andreas Thomas, Mario Thevis

{"title":"Investigations Into the Urinary Metabolite Elimination Profile of the Selective Androgen Receptor Modulator S-23 in Studies Mimicking Contaminated Product Ingestion for Doping Control Purposes","authors":"Hana Alhalabi, Linus Korsmeier, Andreas Thomas, Mario Thevis","doi":"10.1002/bmc.70090","DOIUrl":"https://doi.org/10.1002/bmc.70090","url":null,"abstract":"<p>Selective androgen receptor modulators (SARMs) have repeatedly been reason of adverse analytical findings (AAFs) in routine doping controls. Among these, S-23 has been identified in five AAFs reported in 2022. In addition to intentional doping, inadvertent exposure through contaminated dietary supplements has emerged as a significant concern, purportedly as well as evidently contributing to AAFs involving SARMs. Thus, the differentiation of inadvertent intake and intentional abuse of S-23 is of growing relevance. This study aimed at investigating the urinary concentration profile of microdosed S-23 and to characterize the elimination pattern. Single and multidose administration studies with 1, 10, and 50 μg of S-23 were conducted, and collected urine samples were analyzed by LC–MS/MS following enzymatic hydrolysis and solid-phase extraction. The analytical method was validated for a semiquantitative detection of S-23 and characterized by a limit of detection of 1 pg/mL. A total of 18 metabolites was detected in human in vivo samples following oral administration of microdosed S-23. Moreover, the study demonstrated that a single dose of 1 μg can be detected for an average of up to 253 h, while a single dose of 50 μg can be detected up to 544 h on average.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmc.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871751","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}

引用次数: 0

Liquid Chromatography Combined With Electrospray Ionization Tandem Mass Spectrometry for the Determination and Identification of AZD5462 and Its Metabolites in Rat Plasma 液相色谱-电喷雾串联质谱联用测定大鼠血浆中AZD5462及其代谢物

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-25 DOI: 10.1002/bmc.70095

Congyao You, Yan Zhang, Dece Kong, Tieyi Yang

{"title":"Liquid Chromatography Combined With Electrospray Ionization Tandem Mass Spectrometry for the Determination and Identification of AZD5462 and Its Metabolites in Rat Plasma","authors":"Congyao You, Yan Zhang, Dece Kong, Tieyi Yang","doi":"10.1002/bmc.70095","DOIUrl":"https://doi.org/10.1002/bmc.70095","url":null,"abstract":"<div>\u0000 \u0000 <p>AZD5462, a human RXFP1 agonist, which is undergoing clinical development for the treatment of heart failure. The aim of this study was to develop an ultra-high-performance liquid chromatography-tandem mass spectrometric method for the determination of AZD5462 in rat plasma. After precipitated with acetonitrile, the sample was analyzed on a BEH C<sub>18</sub> column using 0.1% formic acid and acetonitrile as mobile phase with a gradient elution at 40°C within 2 min. The assay showed excellent linearity in the range of 0.1–1000 ng/mL with the correlation coefficient more than 0.995. The precision, accuracy, matrix effect, recovery, and stability met all requirements for the quantitation in plasma samples. The validated method has been further applied to the pharmacokinetic study of AZD5462 in rats. In addition, the metabolism of AZD5462 in rat was investigated by a liquid chromatography-high resolution mass spectrometry. In rat liver microsomes, four metabolites were identified based on their accurate mass and fragment ions. In rat plasma, one glucuronide conjugate was identified. The metabolic pathways of AZD5462 include oxygenation and glucuronidation. This study is the first report on the pharmacokinetics and metabolism of AZD5462, which would provide insights into the effectiveness and toxicity of this drug candidate.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871750","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

A New Discovery: Corydalis yanhusuo Causes Idiosyncratic Hepatotoxicity and Its Potential Mechanisms 延胡索引起特异性肝毒性及其潜在机制的新发现

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-25 DOI: 10.1002/bmc.70093

Longxin Guo, Li Lin, Jun Ling, Shengkai Zhu, Xinyu Li, Minjuan Long, Yingjie Xu, Zhanjiang Hu, Ming Niu, Xu Zhao, Xiaohe Xiao

{"title":"A New Discovery: Corydalis yanhusuo Causes Idiosyncratic Hepatotoxicity and Its Potential Mechanisms","authors":"Longxin Guo, Li Lin, Jun Ling, Shengkai Zhu, Xinyu Li, Minjuan Long, Yingjie Xu, Zhanjiang Hu, Ming Niu, Xu Zhao, Xiaohe Xiao","doi":"10.1002/bmc.70093","DOIUrl":"https://doi.org/10.1002/bmc.70093","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Corydalis yanhusuo</i> W.T.Wang (YHS) is a commonly used traditional Chinese medicine, often prescribed for treating a variety of pains. In recent years, there has been a gradual increase in the number of reports to liver injury caused by YHS and its preparations, but the exact type and mechanism of hepatotoxicity are still unclear. In the present study, we demonstrated that YHS could induce idiosyncratic drug-induced liver injury (IDILI) in the inflammatory activation models. A total of 459 differential genes and 25 differential metabolites were identified by transcriptomics and metabolomics, which were significantly enriched in the TNF and NF-κB signaling pathways as well as glycerophospholipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism. In addition, YHS significantly increased the levels of TNF-α, IL-1β, and IL-6. Therefore, we believe that the mechanism of toxicity may be related to the TNF and NF-κB signaling pathways, with glycerophospholipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism also playing important roles. It provides a reference for the safe and rational use of YHS in clinical practice and contributes to the precise prevention and control of the risk of liver toxicity associated with YHS.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871742","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 Mechanisms of Polygonum orientale L. Against Myocardial Ischemia: An Integrated Analysis Using Ultra-High-Performance Liquid Chromatography–Quadrupole Exactive Orbitrap Mass Spectrometry, Network Pharmacology, and RNA Sequencing 探索何首乌防治心肌缺血的机制：利用超高效液相色谱-四极杆精确轨道阱质谱、网络药理学和 RNA 测序进行综合分析

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-21 DOI: 10.1002/bmc.70089

Chunhua Liu, Changli Fu, Luping Tang, Jieqi Li, Jia Sun, Yuan Lu, Jie Pan, Ting Liu, Yongjun Li, Yonglin Wang, Yong Huang, Yueting Li, Meng Zhou

{"title":"Exploring the Mechanisms of Polygonum orientale L. Against Myocardial Ischemia: An Integrated Analysis Using Ultra-High-Performance Liquid Chromatography–Quadrupole Exactive Orbitrap Mass Spectrometry, Network Pharmacology, and RNA Sequencing","authors":"Chunhua Liu, Changli Fu, Luping Tang, Jieqi Li, Jia Sun, Yuan Lu, Jie Pan, Ting Liu, Yongjun Li, Yonglin Wang, Yong Huang, Yueting Li, Meng Zhou","doi":"10.1002/bmc.70089","DOIUrl":"https://doi.org/10.1002/bmc.70089","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Polygonum orientale</i> L. (PO) represents significant bioactivities in treating myocardial ischemia (MI); however, its underlying mechanisms remain unclear. This study aims to elucidate PO's potential mechanisms in MI using an integrated approach that combines UHPLC–Q-Exactive Orbitrap HRMS, network pharmacology, and RNA-sequencing (RNA-seq). Initially, the chemical constituents of PO were identified using UHPLC–Q-Exactive Orbitrap HRMS. Subsequently, network pharmacology, molecular docking, and RNA-seq were employed to screen potential active components of PO targeting MI and predict their molecular mechanisms. Then, the molecular mechanisms were verified using western blotting and ELISA in MI mice. A total of 45 components were identified from PO, with 14 potential active compounds interacting with 204 MI-related genes. The findings suggest that PO could alleviate heart damage. The RNA-seq results indicated 244 potential targets regulated by PO. Integrating RNA-seq and network pharmacology analyses revealed that the toll-like receptor signaling pathway plays an important role, alongside the PI3K-Akt. Notably, PO reduced the expression of TLR4 and TLR2 while increasing p-Akt and p-PI3K levels in MI mice, leading to decreased inflammatory cytokines and apoptosis-related proteins. This study provides initial evidence that PO inhibits the toll-like signaling pathway and activates PI3K–Akt signaling pathway to exert protective effects against MI.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853046","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

Pharmacokinetics of Oleracrylimide E in Rats Plasma Using UHPLC/-ESI-Q-TOF/MS 用UHPLC/-ESI-Q-TOF/MS研究奥丙烯酰亚胺E在大鼠血浆中的药动学

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-20 DOI: 10.1002/bmc.70067

Zheming Ying, Kaiyun Jiang, Chengyu Wang, Hongzhe Zhang, Junjie Yao, Yingdai Zhao, Xixiang Ying, Yanling Ren

引用次数: 0

Quantification of Methylene Blue and Evaluation of Its Pharmacokinetics in ICR Mice by Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry Using Difluoroacetic Acid 使用二氟乙酸的液相色谱-四极杆飞行时间质谱法定量亚甲基蓝并评估其在 ICR 小鼠体内的药代动力学

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-04-20 DOI: 10.1002/bmc.70080

Seo-jin Park, Juwon Lee, Sangsoo Hwang, Jeong-hyeon Lim, Hyunjin Cho, Young G. Shin

{"title":"Quantification of Methylene Blue and Evaluation of Its Pharmacokinetics in ICR Mice by Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry Using Difluoroacetic Acid","authors":"Seo-jin Park, Juwon Lee, Sangsoo Hwang, Jeong-hyeon Lim, Hyunjin Cho, Young G. Shin","doi":"10.1002/bmc.70080","DOIUrl":"https://doi.org/10.1002/bmc.70080","url":null,"abstract":"<p>Methylene blue (MB), a phenothiazine derivative, is currently under clinical trials for Alzheimer's disease (<span>AD</span>) due to its potential to inhibit tau aggregation, a key pathological process in <span>AD</span>. In this study, we developed and qualified a rapid and reliable liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) method for the quantification of MB in mouse plasma and brain samples. Chromatographic separation was achieved using a PolymerX RP-1 100 Å (50 × 2 mm, 5 μm) column with a mobile phase consisting of water and methanol containing 0.5% difluoroacetic acid, delivered at a flow rate of 0.5 mL/min. Calibration curves were constructed using quadratic regression (weighted 1/concentration<sup>2</sup>) over a range of 3.05–2222.22 ng/mL in both matrices. The method was successfully applied to characterize the pharmacokinetics of MB in male ICR mice, revealing a high systemic clearance (65.64 mL/min/kg) and substantial brain penetration, as indicated by a brain-to-plasma partition coefficient (<i>K</i><sub><i>p,brain</i></sub>) of 23.50 following single intravenous bolus administration. These findings provide critical insights into MB's in vivo behavior and demonstrate the utility of this bioanalytical method for evaluating MB in preclinical studies.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmc.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853037","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}

引用次数: 0