Biomedical Chromatography最新文献_第3页

Quality by Design-Based Stability-Indicating RP-HPLC Method for Diminazene Diaceturate in Veterinary Formulation Supported by LC–MS Characterization of Degradation Products 基于设计的稳定性指示反相高效液相色谱法测定兽药制剂中二乙酸迪纳苯的质量，并支持降解产物的LC-MS表征。

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-03-16 DOI: 10.1002/bmc.70428

Sumedha V. Shetye, Archana S. Gurjar

{"title":"Quality by Design-Based Stability-Indicating RP-HPLC Method for Diminazene Diaceturate in Veterinary Formulation Supported by LC–MS Characterization of Degradation Products","authors":"Sumedha V. Shetye, Archana S. Gurjar","doi":"10.1002/bmc.70428","DOIUrl":"10.1002/bmc.70428","url":null,"abstract":"<div>\u0000 \u0000 <p>This study focuses on the development and validation of the Quality by Design RP-HPLC method for diminazene diaceturate with fragmentation study by LC–MS/MS. The central composite design was employed to optimize critical factors: mobile phase ratio, flow rate, and wavelength. Analysis was conducted on Xterra C18 column with mobile phase composed of 0.1% triethylamine buffer: methanol (80:20% v/v) and flow rate 0.8 mL/min at 255 nm, with retention at 4.34 min. ICH Q1A(R2) guidelines, acid stress degradation study showed maximum degradation of 16.03%. The fragmentation pathway exhibited prominent product ions at m/z 518, 284, 285, and 268. Linearity was observed over the concentration range (50–100 μg/mL) with a regression coefficient of 0.9997. Limit of detection and limit of quantification values were observed to be 7.772 and 23.566 μg/mL, respectively; % RSD of each parameter was found to be less than 2. The validated method proved suitable for assay of marketed veterinary formulation, yielding recovery of 93.22%, with clear separation of the stabilizer phenazone. This study focuses on the development of a stability indicating RP-HPLC method using a Quality by Design approach with LC–MS compatible triethylamine buffer, enabling degradation product characterization while maintaining a regulatory-compliant RP-HPLC method suitable for routine and stability testing of diminazene diaceturate in pharmaceutical laboratories.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466309","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 Mechanism of Gentiana veitchiorum in Treating Asthma Through Network Pharmacology, Untargeted Metabolomics, and Molecular Docking Technology 通过网络药理学、非靶向代谢组学和分子对接技术探索龙胆治疗哮喘的机制。

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-03-16 DOI: 10.1002/bmc.70420

Hongting Mo, Qiuye Tian, Qiangfeng Li, Tingliang Xu

{"title":"Exploring the Mechanism of Gentiana veitchiorum in Treating Asthma Through Network Pharmacology, Untargeted Metabolomics, and Molecular Docking Technology","authors":"Hongting Mo, Qiuye Tian, Qiangfeng Li, Tingliang Xu","doi":"10.1002/bmc.70420","DOIUrl":"10.1002/bmc.70420","url":null,"abstract":"<div>\u0000 \u0000 <p>To investigate the mechanism of <i>Gentiana veitchiorum</i> in treating asthma using network pharmacology and untargeted metabolomics, with validation by molecular docking. LC–MS/MS was employed to comprehensively analyze metabolites in flowers of <i>G. veitchiorum</i> collected from Taoheyuan National Wetland Park. Asthma-related compounds were retrieved from TCMSP and compared with identified metabolites. Potential targets were predicted using TCMSP and Uniprot, while asthma-related targets were acquired from GeneCards. Common targets were selected to construct compound-target and protein–protein interaction networks using Cytoscape and STRING. Functional enrichment analysis was performed via DAVID. The top three bioactive components with the most targets were molecularly docked with the top 10 hub targets. In total, 904 metabolites were identified. Among them, 23 matched known anti-asthma compounds from TCMSP. Intersection analysis revealed 388 common targets between drug and disease. Kaempferol, luteolin, and isorhamnetin showed the highest number of target associations. Molecular docking demonstrated strong binding between kaempferol and PRKACA. <i>G. veitchiorum</i> may treat asthma through active compounds like kaempferol, luteolin, and isorhamnetin, modulating core genes such as TP53, AKT1, IL6, TNF, and PRKACA. This study provides a scientific foundation for further clinical research and development of <i>G. veitchiorum</i> in treating asthma and other diseases.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466311","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 Effects of Siegesbeckiae Herba and Its Fractionated Components on Neuroendocrine Metabolism in Rats With Heat Syndrome Based on Metabolomics 基于代谢组学研究荆芥及其分离成分对热证大鼠神经内分泌代谢的影响。

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-03-02 DOI: 10.1002/bmc.70406

Ajiao Hou, Chao Yu, Guoqing Shan, Jiaxu Zhang, Haixue Kuang, Liu Yang, Hai Jiang

{"title":"Exploring the Effects of Siegesbeckiae Herba and Its Fractionated Components on Neuroendocrine Metabolism in Rats With Heat Syndrome Based on Metabolomics","authors":"Ajiao Hou, Chao Yu, Guoqing Shan, Jiaxu Zhang, Haixue Kuang, Liu Yang, Hai Jiang","doi":"10.1002/bmc.70406","DOIUrl":"10.1002/bmc.70406","url":null,"abstract":"<div>\u0000 \u0000 <p>Siegesbeckiae herba (SH) with a cold nature exerts therapeutic effects including dispelling wind-dampness, benefiting joints. This study aims to explore the effects of SH and its fractionated components on neuroendocrine metabolism functions in heat syndrome rats and to clarify the property attribution of each component. The main components of SH were isolated via modern separation techniques. A heat syndrome rat model was established by administration of levothyroxine sodium. Metabolomics was employed to screen differential expressed metabolites (DEMs) and metabolic pathways, and indicators related to neuroendocrine metabolism were determined. A total of 107 DEMs involving 17 pathways were screened out. It was found that SH and its fractions could inhibit the abnormally activated metabolic pathways in hot syndrome rats. Among them, the terpenoids fraction showed the optimal regulatory effect on neurotransmitter imbalance, excessive activation of the hypothalamic–pituitary–thyroid axis, and energy/substance metabolism disorders and was confirmed as the main material basis for the cold nature of SH. This study demonstrates that SH and its fractionated components exert therapeutic effects on heat syndromes by regulating the neuroendocrine energy metabolism and related pathways. This provides scientific support for the clinical syndrome differentiation application and further development of SH.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324404","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

Antibiotic-Mediated Microbiota Depletion Suggests an Association Between Gastric Juice Dysbacteriosis and Abnormal Bile Acid Metabolism in Chronic Atrophic Gastritis Rats 慢性萎缩性胃炎大鼠胃液菌群失调与胆汁酸代谢异常相关

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-02-27 DOI: 10.1002/bmc.70404

Yan Zhang, Ruonan Zhang, Guohong Wang, Yuetao Liu

{"title":"Antibiotic-Mediated Microbiota Depletion Suggests an Association Between Gastric Juice Dysbacteriosis and Abnormal Bile Acid Metabolism in Chronic Atrophic Gastritis Rats","authors":"Yan Zhang, Ruonan Zhang, Guohong Wang, Yuetao Liu","doi":"10.1002/bmc.70404","DOIUrl":"10.1002/bmc.70404","url":null,"abstract":"<div>\u0000 \u0000 <p>Current research on chronic atrophic gastritis (CAG) has primarily focused on intestinal flora, while the role of gastric juice microecology remains poorly understood. This study investigated whether alterations in gastric juice microbiota and bile acid (BA) profiles are associated with CAG under microbiota perturbation. A CAG rat model was designed by a multifactor modeling method, and an antibiotic cocktail (Abx) was administered to deplete gastrointestinal microbiota. Full-length 16S rRNA gene sequencing and LC–MS technology were conducted to characterize microbial composition and metabolite profiles in gastric juice. An integrated strategy combining microbiome and metabolome data was employed to validate associations between microbiota and metabolites. CAG rats exhibited elevated proinflammatory cytokines and lipopolysaccharide (LPS) levels in gastric juice, accompanied by dysbacteriosis and aberrant BA profiles. After antibiotic treatment, LPS level and bile salt hydrolase (BSH) activity were reduced, along with the lower abundances of LPS-producing bacteria and multiple BA levels. Correlation analysis demonstrated a positive association between deoxycholic acid (DCA) and LPS-producing bacteria (<i>Escherichia coli</i>). These findings revealed that gastric juice dysbacteriosis and abnormal BA metabolism were relevant to the inflammatory status of CAG. This study provided multi-omics evidence supporting a potential involvement of gastric juice microecological imbalance in CAG progression.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301510","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

Quality by Design–Based RP-HPLC Method for Simultaneous Estimation of 4-Hydroxytamoxifen and Thymoquinone in Liposomal Formulation 基于设计的反相高效液相色谱法同时测定脂质体制剂中4-羟他莫昔芬和百里醌的质量。

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-02-27 DOI: 10.1002/bmc.70393

Pavithra Pradeep Prabhu, Cynthia Lizzie Lobo, L. B. Vishal, Akhil Nair, Aravinda Pai, Swastika Maity, Vasudev Pai, Saina Bijanzadeh, Akhilesh Dubey

{"title":"Quality by Design–Based RP-HPLC Method for Simultaneous Estimation of 4-Hydroxytamoxifen and Thymoquinone in Liposomal Formulation","authors":"Pavithra Pradeep Prabhu, Cynthia Lizzie Lobo, L. B. Vishal, Akhil Nair, Aravinda Pai, Swastika Maity, Vasudev Pai, Saina Bijanzadeh, Akhilesh Dubey","doi":"10.1002/bmc.70393","DOIUrl":"10.1002/bmc.70393","url":null,"abstract":"<div>\u0000 \u0000 <p>Developing a method for the simultaneous quantification of drugs in combination formulations is crucial for optimizing combination therapy. 4-Hydroxytamoxifen (4-OHT) and thymoquinone exhibit synergistic activity in breast cancer treatment, yet no robust analytical method exists for their simultaneous estimation in liposomal systems. This study aimed to design, optimize and validate an RP-HPLC method for quantifying both drugs using an analytical quality by design (AQbD) approach. An analytical target profile (ATP) was defined, and risk assessment using an Ishikawa diagram identified mobile phase composition, flow rate and column temperature as critical parameters. Method optimization was performed using a Box–Behnken Design, evaluating effects on retention times, peak areas, tailing factors and resolution. Optimal conditions included a 90:10 methanol:aqueous mobile phase, 0.5 mL/min flow rate and 35°C column temperature. The method was validated per ICH Q2(R1) guidelines, demonstrating excellent sensitivity (LOD 0.69–0.29 μg/mL), accuracy (95%–105% recovery) and precision (RSD < 2%). The method was successfully applied for drug estimation in liposomal formulations, ex vivo permeation, cytotoxicity and cellular uptake studies. Liposomal gels showed high entrapment efficiency, enhanced drug release, permeation and cellular uptake. Analytical Eco-Scale assessment confirmed excellent green performance.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316274","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

Therapeutic Drug Monitoring of Clobazam, Perampanel, and Lacosamide Using a UPLC-MS/MS Method: Analysis of 5-Year Experience in a Large Cohort of Pediatric Epilepsy Patients From China 采用UPLC-MS/MS方法监测氯巴赞、Perampanel和拉科沙胺的治疗药物：中国儿童癫痫患者5年大队列的经验分析

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-02-26 DOI: 10.1002/bmc.70403

Ting Zhao, Hui-Lan Zhang, Jing Yu, Jie Feng, Hong-Jian Li, Yan Sun, Lu-Hai Yu

{"title":"Therapeutic Drug Monitoring of Clobazam, Perampanel, and Lacosamide Using a UPLC-MS/MS Method: Analysis of 5-Year Experience in a Large Cohort of Pediatric Epilepsy Patients From China","authors":"Ting Zhao, Hui-Lan Zhang, Jing Yu, Jie Feng, Hong-Jian Li, Yan Sun, Lu-Hai Yu","doi":"10.1002/bmc.70403","DOIUrl":"10.1002/bmc.70403","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to develop an ultra high-performance liquid chromatography–mass spectrometry (UPLC-MS/MS) method to quantify clobazam, perampanel, and lacosamide plasma concentrations in pediatric epilepsy patients. Elution was performed using a gradient elution program, with a mobile phase composed of 0.01% formic acid in water and 0.01% formic acid in acetonitrile. The flow rate was 0.6 mL/min. The injector temperature was 10°C. The injection volume was 4 μL. Linearity, sensitivity, precision, accuracy, specificity, carryover, and extraction recovery were evaluated. Therapeutic drug monitoring data of 1132 samples were analyzed. The method was linear within 10–600 ng/mL, 100–2000 ng/mL, and 1.0–30.0 μg/mL for clobazam, perampanel, and lacosamide, respectively (<i>r</i> ≥ 0.998). The results indicated that the within-run and between-run precision coefficient of variation (CV %) did not exceed 15.0%, and that the accuracy (bias) ranged from −8.3% to 13.6%. Recovery ranged from 90.9% to 108.1%. All plasma samples could be maintained for up to 3 h at ambient temperature, 24 h at 4°C, 30 days at −30°C, and after successive freeze–thaw cycles in the absence of significant degradation. We successfully developed a simple and rapid LC-MS/MS method for the simultaneous measurement of three new generation ASMs, and successfully applied it to clinical practice.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301652","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 Simple and Sensitive LC-MS/MS Method for Quantification of Capsaicin in Human Plasma and Its Application to a Clinical Pharmacokinetic Study 简便、灵敏的LC-MS/MS定量人血浆中辣椒素及其在临床药动学研究中的应用

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-02-26 DOI: 10.1002/bmc.70405

Xiaoyu Xu, Wenyuan Qi, Juan Wang, Lei Yang, Xiaohui Liu, Wei Xue, Kexin Li

{"title":"A Simple and Sensitive LC-MS/MS Method for Quantification of Capsaicin in Human Plasma and Its Application to a Clinical Pharmacokinetic Study","authors":"Xiaoyu Xu, Wenyuan Qi, Juan Wang, Lei Yang, Xiaohui Liu, Wei Xue, Kexin Li","doi":"10.1002/bmc.70405","DOIUrl":"10.1002/bmc.70405","url":null,"abstract":"<div>\u0000 \u0000 <p>Capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, is used topically for neuropathic pain. Its minimal systemic absorption necessitates highly sensitive quantification methods to accurately assess systemic exposure. This study aimed to develop and validate a simple, rapid, and highly sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the quantification of capsaicin in human plasma. Plasma samples (50 μL) were prepared by a simple protein precipitation using acetonitrile, with capsaicin-d3 as the internal standard (IS). Chromatographic separation was performed on a Waters Xbridge C<sub>18</sub> column (2.1 × 50 mm, 3.5 μm) with a 3-min gradient elution using 1% formic acid in water and acetonitrile. Detection was conducted on a triple quadrupole tandem mass spectrometer in positive electrospray ionization (ESI) mode, utilizing multiple-reaction monitoring (MRM). The assay was validated over the linear range of 0.05–50 ng/mL. The method demonstrated excellent precision (CV% ≤ 11.62%) and accuracy (RE% within ±13.60%), with high recovery (>95%). Stability was confirmed under various conditions relevant to clinical sample handling. The validated method was successfully applied to a pharmacokinetic study involving 24 patients with knee osteoarthritis receiving a topical capsaicin liniment, demonstrating its suitability for clinical applications.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301543","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 Liquid Chromatograph–Tandem Mass Spectrometry Method for Quantifying Ganciclovir in Dried Blood Spots for Therapeutic Drug Monitoring 液相色谱-串联质谱法测定干血斑中更昔洛韦用于治疗药物监测的建立与验证。

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-02-24 DOI: 10.1002/bmc.70411

Naoki Tamura, Kotaro Itohara, Suguru Kouyama, Yumi Kitahiro, Kazuhiro Yamamoto, Tomohiro Omura, Toshiyasu Sakane, Jun Saegusa, Ikuko Yano

{"title":"Development and Validation of a Liquid Chromatograph–Tandem Mass Spectrometry Method for Quantifying Ganciclovir in Dried Blood Spots for Therapeutic Drug Monitoring","authors":"Naoki Tamura, Kotaro Itohara, Suguru Kouyama, Yumi Kitahiro, Kazuhiro Yamamoto, Tomohiro Omura, Toshiyasu Sakane, Jun Saegusa, Ikuko Yano","doi":"10.1002/bmc.70411","DOIUrl":"10.1002/bmc.70411","url":null,"abstract":"<div>\u0000 \u0000 <p>Valganciclovir (VGCV) is the first-line drug for preemptive therapy of cytomegalovirus (CMV) infection. However, even at standard doses, plasma concentrations of the active metabolite ganciclovir (GCV) show substantial inter-individual variability. To ensure therapeutic efficacy and minimize adverse effects, therapeutic drug monitoring (TDM) based on the area under the concentration–time curve (AUC) is essential. Yet, conventional TDM via venous blood sampling is invasive and unsuitable for frequent monitoring. In this study, we aimed to develop a simple and minimally invasive method for GCV quantification using dried blood spots (DBS) combined with liquid chromatography–tandem mass spectrometry (LC–MS/MS). The method demonstrated a good linearity over a concentration range of 0.25–16 μg/mL and satisfied the validation criteria for accuracy and precision. It showed acceptable stability for up to 7 days under refrigerated conditions. Methanol was identified as the optimal extraction solvent, allowing for a simplified sample pretreatment without the need for ultrasonic processing. While hematocrit levels affected spot size and quantification accuracy, reliable measurements were obtained within the 30%–50% hematocrit range. The established DBS-based LC–MS/MS method provides a promising, minimally invasive approach for TDM of GCV in the management of CMV infections.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282139","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

Metabolomic and Genomic Insights Into Adverse Events in Paroxysmal Atrial Tachycardia 阵发性房性心动过速不良事件的代谢组学和基因组学研究。

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-02-24 DOI: 10.1002/bmc.70409

Qiuyu Wang, Lianfeng Liu, Peng Liu, Tingting Lv, Yifei Wang, Qing Li, Yuanwei Liu, Ping Zhang

{"title":"Metabolomic and Genomic Insights Into Adverse Events in Paroxysmal Atrial Tachycardia","authors":"Qiuyu Wang, Lianfeng Liu, Peng Liu, Tingting Lv, Yifei Wang, Qing Li, Yuanwei Liu, Ping Zhang","doi":"10.1002/bmc.70409","DOIUrl":"10.1002/bmc.70409","url":null,"abstract":"<div>\u0000 \u0000 <p>Paroxysmal atrial tachycardia (PAT) is a supraventricular arrhythmia associated with increased risk of atrial fibrillation (AF) and adverse cardiovascular events, but mechanisms underlying adverse outcomes remain unclear. We integrated serum metabolomics (LC–MS/MS), pathway enrichment, transcriptomic profiling, and in vitro validation in a PAT-onset cohort (five patients and five matched controls) and a PAT-events cohort (10 with and 10 without adverse events). Differential metabolites and pathways were identified, and GSEA focused on ABC transporters and alanine, aspartate, and glutamate metabolism. PAT exhibited metabolic dysregulation enriched in amino-acid metabolism and inflammation. Taurocholic acid was increased in PAT with adverse events and showed strong predictive value. Integrative analyses highlighted ABC transporter and alanine/aspartate/glutamate metabolism pathways. ABCA9 was upregulated, whereas ABCB10 and ABCC6 were downregulated in patient data and tachycardia transcriptomics, and these changes were confirmed in paced HL-1 atrial myocytes. ADSS1, AGXT2, and ASS1 were downregulated, indicating disrupted aspartate-linked metabolism; reduced ABCB10 suggested impaired mitochondrial homeostasis. Overall, PAT is characterized by metabolic remodeling involving ABC transporter dysfunction, amino-acid metabolic impairment, mitochondrial dysfunction, and vascular instability, supporting biomarker-guided risk stratification and targeted intervention.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282175","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 Precolumn Derivatization LC-MS/MS Method for the Determination of Methoxamine Enantiomers in Rat Plasma: Application to Stereoselective Pharmacokinetic Analysis 柱前衍生LC-MS/MS测定大鼠血浆中甲氧沙明对映体的新方法：在立体选择药代动力学分析中的应用。

IF 1.7 4区医学

Biomedical Chromatography Pub Date : 2026-02-23 DOI: 10.1002/bmc.70408

Siqi Li, Huan Gong, Ting Zhao, Nan Tao, Yan Li, Yan Cui

{"title":"A New Precolumn Derivatization LC-MS/MS Method for the Determination of Methoxamine Enantiomers in Rat Plasma: Application to Stereoselective Pharmacokinetic Analysis","authors":"Siqi Li, Huan Gong, Ting Zhao, Nan Tao, Yan Li, Yan Cui","doi":"10.1002/bmc.70408","DOIUrl":"10.1002/bmc.70408","url":null,"abstract":"<div>\u0000 \u0000 <p>Methoxamine is a selective α-adrenergic receptor agonist used to manage hypotension during anesthesia and prevent cardiac arrhythmias. Erythro-methoxamine, a racemic mixture, is clinically administered in this form. Previous studies revealed that the (1<i>R</i>,2<i>S</i>)-enantiomer exhibits stronger pharmacological activity than the (1<i>S</i>,2<i>R</i>)-enantiomer, highlighting the need for stereoselective pharmacokinetic evaluation. Given the high sensitivity, excellent stereoselectivity, and resistance to racemization exhibited by (<i>S</i>)-<i>N</i>-(4-nitrophenoxycarbonyl) phenylalanine 2-methoxyethyl ester [(<i>S</i>)-NIFE], this study pioneered its novel application as the chiral derivatization reagent for methoxamine prior to chromatographic analysis. Based on precolumn derivatization, a sensitive, efficient, and straightforward LC-MS/MS method was developed to determine the two enantiomeric derivatives of erythro-methoxamine. DHBA was selected as the internal standard. After protein precipitation, the derivatives were analyzed in positive ESI-MRM mode. The method showed good linearity over 0.5–250.0 ng·mL<sup>−1</sup> with an LLOQ of 0.5 ng·mL<sup>−1</sup>. Intraday and interday RSDs were below 9.7%, and recoveries exceeded 86.2%. The validated method was successfully applied to the first stereoselective pharmacokinetic study of erythro-methoxamine in rat plasma. Significant differences in AUC, <i>t</i><sub>1/2</sub>, Vd, and CL were observed, confirming its suitability for in vivo pharmacokinetic analysis and providing evidence for the stereoselective disposition of methoxamine enantiomers.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"40 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275623","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