Biomedical Chromatography最新文献_第5页

LC-MS/MS Analyzing Praziquantel and 4-Hydroxypraziquantel Enantiomers in Black Goat Plasma and Mechanism of Stereoselective Pharmacokinetics 黑山羊血浆中吡喹酮和4-羟基吡喹酮对映体的LC-MS/MS分析及立体选择药动学机制

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-11 DOI: 10.1002/bmc.6082

Xiaoxi Du, Basma Saleh, Xiarong Li, Xiantong Zheng, Xiaogui Shu, Rong Liu, Limin He

{"title":"LC-MS/MS Analyzing Praziquantel and 4-Hydroxypraziquantel Enantiomers in Black Goat Plasma and Mechanism of Stereoselective Pharmacokinetics","authors":"Xiaoxi Du, Basma Saleh, Xiarong Li, Xiantong Zheng, Xiaogui Shu, Rong Liu, Limin He","doi":"10.1002/bmc.6082","DOIUrl":"10.1002/bmc.6082","url":null,"abstract":"<div>\u0000 \u0000 <p>Praziquantel (PZQ) is the most effective treatment for schistosomiasis, commonly administered as a racemic mixture of the two enantiomers. Despite many reports on the pharmacokinetics of PZQ, the stereoselective pharmacokinetics of PZQ and its major metabolite 4-hydroxypraziquantel (4-OH-PZQ) remain poorly understood in goats. In this study, the chiral LC-MS/MS method was further optimized for separating and quantifying PZQ, <i>trans</i>-4-OH-PZQ, and <i>cis</i>-4-OH-PZQ and their enantiomers and then applied for the molecular pharmacokinetics of three analytes in black goat plasma. The findings showed that PZQ was rapidly absorbed and metabolized to 4-OH-PZQ. The C<sub>max</sub> of <i>trans</i>-4-OH-PZQ was about 3 times and 6 times higher than those of <i>cis</i>-4-OH-PZQ and PZQ, respectively. The stereoselectivity of the PZQ and <i>cis</i>-4-OH-PZQ enantiomers was insignificant in black goat plasma (<i>p</i> > 0.05), whereas the <i>trans</i>-4-OH-PZQ enantiomers exhibited obvious stereoselectivity (<i>p</i> < 0.05). The C<sub>max</sub> of S-trans-4-OH-PZQ were ~3.1 times higher than that of R-<i>trans</i>-4-OH-PZQ. Further computer simulations indicated that these differences in the stereoselectivity might mainly stem from the different binding energies of the corresponding R- and S-enantiomers of the target analytes to black goat plasma albumin. It has guiding significance for the research on the stereoselectivity of chiral veterinary drugs and their precision medication.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963744","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

Unique Research for Developing a Full Factorial Design Evaluated Liquid Chromatography Technique for Estimating Budesonide and Formoterol Fumarate Dihydrate in the Presence of Specified and Degradation Impurities in Dry Powder Inhalation 基于全析因设计的液相色谱法评价干粉吸入中布地奈德和富马酸福莫特罗的杂质含量。

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-10 DOI: 10.1002/bmc.6062

Lova Gani Raju Bandaru, Naresh Konduru, Leela Prasad Kowtharapu, Rambabu Gundla, Phani Raja Kanuparthy, Naresh Kumar Katari

{"title":"Unique Research for Developing a Full Factorial Design Evaluated Liquid Chromatography Technique for Estimating Budesonide and Formoterol Fumarate Dihydrate in the Presence of Specified and Degradation Impurities in Dry Powder Inhalation","authors":"Lova Gani Raju Bandaru, Naresh Konduru, Leela Prasad Kowtharapu, Rambabu Gundla, Phani Raja Kanuparthy, Naresh Kumar Katari","doi":"10.1002/bmc.6062","DOIUrl":"10.1002/bmc.6062","url":null,"abstract":"<p>A simple LC method has been developed and validated for estimating budesonide (epimer B + A) and formoterol fumarate dihydrate in dry powder inhalation. The development results of this study make it very significant. The degradation and process impurities in EP and ChP were identified in addition to budesonide and formoterol fumarate. As of yet, no one has reported all impurities using a single method. It is a unique research because it analyzes APSD (Aerodynamic Particle Size Distribution), DDU (Delivered Dose Uniformity), BU (Blend Uniformity), Assay, and cleaning test samples. It enhances the quality of medicine and separates all organic impurities and isomers through a suitable stationary phase (YMC-Pack Pro C18, 150 × 4.6 mm × 3 μm). We optimized the chromatographic conditions: Injection volume was 20 μL, and flow rate was 1.0 mL/min. The wavelength was optimized at 220 nm. After experimental and validation results. An example is A, which contains sodium dihydrogen orthophosphate monohydrate, sodium 1-decane sulfonate, adjusted pH 3.0, and acetonitrile at a ratio of 80:20 (v/v), and B, which contains pH 3.0 buffer and acetonitrile at a ratio of 20:80 (v/v) respectively. In addition to being optimized, the test method was validated according to ICH Q2(R2).</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943450","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

Noval Selective Ligand-Extraction of Bioactive Components in Complex Natural Products Applying Immobilized Multi-Target Magnetic Beads 应用固定化多靶点磁珠的新型选择性配体萃取复杂天然产物中的生物活性成分。

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-09 DOI: 10.1002/bmc.6060

Chen Wang, Xueying Qin, Ying Wang, Weiping Wang, Shuai Sun, Hongsen Wang, Shiyu Li, Xiao Dai, Xianhong Zhu, Xun Gao, Kunming Qin, Qing Zhang

引用次数: 0

Validated HPLC-UV Method for the Quantification of a Novel BCr-Abl 1 Inhibitor, Vodobatinib, in Rat Plasma: Application to a Pharmacokinetic Study 高效液相色谱-紫外法定量大鼠血浆中新型BCr-Abl - 1抑制剂Vodobatinib：在药代动力学研究中的应用

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-08 DOI: 10.1002/bmc.6077

Sandeep Kaddare, Ashok Zakkula, Rama Murthi Bestha, Keerthana Madipelli, Rajnish Kumar, Yogesh Balaji Biradar, Niranjan Veerla, Sreekanth Dittakavi, Ramesh Mullangi

{"title":"Validated HPLC-UV Method for the Quantification of a Novel BCr-Abl 1 Inhibitor, Vodobatinib, in Rat Plasma: Application to a Pharmacokinetic Study","authors":"Sandeep Kaddare, Ashok Zakkula, Rama Murthi Bestha, Keerthana Madipelli, Rajnish Kumar, Yogesh Balaji Biradar, Niranjan Veerla, Sreekanth Dittakavi, Ramesh Mullangi","doi":"10.1002/bmc.6077","DOIUrl":"10.1002/bmc.6077","url":null,"abstract":"<div>\u0000 \u0000 <p>Vodobatinib is a Bcr-Abl 1 inhibitor, currently entering into Phase 2 clinical trials as a potential drug to treat glioblastoma patients. In the present work, a validated high-performance liquid chromatography (HPLC) detection method for the quantification of vodobatinib in rat plasma was established. Sample preparation involved liquid–liquid extraction method. The chromatographic separation of vodobatinib and the IS was accomplished on an XBridge C<sub>18</sub> column using 10 mM ammonium acetate and acetonitrile in gradient condition. The flow-rate and injection volume were 0.8 mL/min and 20 μL, respectively. The eluent was detected at 310 nm. Vodobatinib and the IS eluted at 7.5 and 5.9 min, respectively, with a total run time of 10 min. Validation tests were performed according to FDA requirements. The established method showed good linearity in the range of 50.5–6534 ng/mL. Interday and intraday coefficients of variations were < 5.11%. Stability studies, dilution integrity, and incurred sample reanalysis met the acceptance criteria. Subsequently, the validated HPLC method was used to study the disposition kinetics of vodobatinib in rats.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943456","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 Integrated With Network Pharmacology to Investigate the Potential Mechanism of Lu-Jiao Fang Inhibited Endothelial-to-Mesenchymal Transition in Pressure Overload–Induced Cardiac Fibrosis 药代动力学结合网络药理学研究鹿角方抑制压力过载致心肌纤维化内皮向间质转化的可能机制。

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-08 DOI: 10.1002/bmc.6075

Xiaoli Shi, Jingya Ma, Wei Liu, Jie Shen, Guanglin Xu, Jianwei Zhang, Li Liu

{"title":"Pharmacokinetics Integrated With Network Pharmacology to Investigate the Potential Mechanism of Lu-Jiao Fang Inhibited Endothelial-to-Mesenchymal Transition in Pressure Overload–Induced Cardiac Fibrosis","authors":"Xiaoli Shi, Jingya Ma, Wei Liu, Jie Shen, Guanglin Xu, Jianwei Zhang, Li Liu","doi":"10.1002/bmc.6075","DOIUrl":"10.1002/bmc.6075","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study was to investigate the potential mechanism of Lu-Jiao Fang (LJF) inhibiting endothelial-to-mesenchymal transition (EndMT) in pressure overload-induced cardiac fibrosis. Pharmacokinetic behaviors of the ingredients of LJF were evaluated by LC-MS/MS analysis. Then putative pathways by which LJF regulates EndMT were analyzed by network pharmacology and verified in transverse aortic constriction–induced cardiac fibrosis rats. Loganin, morroniside, salidroside, isopsoralen, and psoralen showed higher plasma, left and right ventricular C<sub>max</sub> and AUC<sub>0–t</sub> values than hesperidin, specnuezhenide, and icariside II. Twenty-four potential targets related to EndMT were identified, which were mainly involved in relaxin signaling pathway. AKT1, TP53, MMP9, HIF1A, Snail1, and MMP2 were key therapeutic targets in protein–protein interaction network. LJF reversed cardiac dysfunction, left ventricular dilation, and fibrosis and significantly downregulated collagen type I and III and EndMT regulators (Snail1 and Twist1) mRNA expression. In relaxin signaling pathway, the RXFP1 protein expression increased by 22.52%, and the protein phosphorylation of Smad2 and Smad3 decreased by 33.52% and 12.79%, in response to the treatment with LJF. This study initially revealed the EndMT inhibition effects and molecular mechanisms of LJF in cardiac fibrosis, providing a reference basis for the promotion of LJF in the clinic.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943449","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

An Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for the Determination of Deoxycholic Acid and Application to a Pharmacokinetic Study in Human Plasma 超高效液相色谱-串联质谱法测定脱氧胆酸及其在人血浆药代动力学研究中的应用。

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-08 DOI: 10.1002/bmc.6076

Wanlin Xi, Diyi Fu, Ni Wu, Fei Liu, Cuixia Zhang, Ruijie Wan, Zhen Wu, Rui Chen, Qian Zhao

{"title":"An Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for the Determination of Deoxycholic Acid and Application to a Pharmacokinetic Study in Human Plasma","authors":"Wanlin Xi, Diyi Fu, Ni Wu, Fei Liu, Cuixia Zhang, Ruijie Wan, Zhen Wu, Rui Chen, Qian Zhao","doi":"10.1002/bmc.6076","DOIUrl":"10.1002/bmc.6076","url":null,"abstract":"<div>\u0000 \u0000 <p>Deoxycholic acid (DCA) injection is applied in treating moderate to severe submental bulge or facial fullness caused by excessive submental fat accumulation. Using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) technology, which was swiftly, precisely, and reliably confirmed, DCA was determined in human plasma with low quantification limits of 56 ng/mL. We selected six healthy individual blank human plasma with low concentrations of endogenous DCA and mixed them to prepare standard curve samples. The samples were purified by the protein precipitation technique and then separated using a BEH C18 column (2.1 × 50 mm, 1.7 μm). Using multiple reaction monitoring (MRM) and electrospray ionization (ESI) sources operating in negative mode, the mass was identified and measured. The precursor-to-product ion transitions were observed at m/z 391.2<sup>−</sup> → 345.2<sup>−</sup> and m/z 395.2<sup>−</sup> → 349.2<sup>−</sup> for DCA and DCA-d<sub>4</sub> (isotope internal standard), respectively. This method was thoroughly validated, encompassing assessments of linearity, sensitivity, precision, selectivity, stability, matrix effect, accuracy, carryover, and recovery. In a word, the validation results demonstrated that this method exhibited sensitivity, accuracy, and reproducibility and could effectively be utilized for studying the pharmacokinetic properties of DCA in a randomized, parallel, controlled, Phase I clinical trial.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943435","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

Farfarae Flos Mitigates Cigarette Smoking-Induced Lung Inflammation by Regulating the Lysophosphatidylcholine Biosynthesis and Tryptophan Metabolism Farfarae Flos通过调节溶血磷脂酰胆碱生物合成和色氨酸代谢减轻吸烟引起的肺部炎症。

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-08 DOI: 10.1002/bmc.6072

Aoqi Liu, Siyao Li, Xianlong Dong, Xuemei Qin, Zhenyu Li

{"title":"Farfarae Flos Mitigates Cigarette Smoking-Induced Lung Inflammation by Regulating the Lysophosphatidylcholine Biosynthesis and Tryptophan Metabolism","authors":"Aoqi Liu, Siyao Li, Xianlong Dong, Xuemei Qin, Zhenyu Li","doi":"10.1002/bmc.6072","DOIUrl":"10.1002/bmc.6072","url":null,"abstract":"<div>\u0000 \u0000 <p>An increased risk of developing respiratory diseases has been linked to exposure to cigarette smoking (CS). The flower buds of <i>Tussilago farfara</i> L., also known as Farfarae Flos (FF), can be used for the treatment of cough, bronchitis, and asthmatic disorders in China. In the present study, we used lung and fecal metabolomics, as well as the intestinal flora analysis, aimed to investigate the protective effect of FF against the CS exposure induced lung inflammation on mice. The results showed that FF administration could relieve the lung inflammation as demonstrated by lung index, interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels, as well as the pulmonary pathological change. The lung metabolomics coupled with molecular docking showed that FF could alleviate lung inflammation by regulating lysophosphatidylcholine biosynthesis through the caffeoyl quinic acids distributed in the lung tissue. In addition, fecal metabolome coupled with 16S rRNA gene sequencing showed that FF could regulate the tryptophan metabolism by regulating the intestinal flora disorders. This study provided new insights of FF to relieve CS-induced pulmonary inflammation with the multimechanism.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943437","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

Integrating Plasma Metabolomics, Network Pharmacology, and Experimental Validation to Investigate the Action Mechanism of Qiangxin Lishui Prescription in Chronic Heart Failure 结合血浆代谢组学、网络药理学和实验验证探讨强心丽水方治疗慢性心力衰竭的作用机制。

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-02 DOI: 10.1002/bmc.6065

Yong Jiang, Wenjun Ji, Ying Lu, Qin Wang, Linwei Chen

{"title":"Integrating Plasma Metabolomics, Network Pharmacology, and Experimental Validation to Investigate the Action Mechanism of Qiangxin Lishui Prescription in Chronic Heart Failure","authors":"Yong Jiang, Wenjun Ji, Ying Lu, Qin Wang, Linwei Chen","doi":"10.1002/bmc.6065","DOIUrl":"10.1002/bmc.6065","url":null,"abstract":"<div>\u0000 \u0000 <p>The high mortality rate of chronic heart failure (CHF) makes it a primary battlefield in the field of cardiovascular diseases. Qiangxin Lishui Prescription (QLP) is a traditional Chinese medicine (TCM) prescription used clinically for treating CHF, but its underlying mechanism remains unclear. This study integrated plasma metabolomics, network pharmacology, and experimental validation to reveal the pharmacological effects of QLP and its potential mechanism of anti-CHF. Using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS/MS), 119 absorbed prototype compounds of QLP were identified from rat plasma. By applying network pharmacology and molecular docking techniques, a QLP absorption components–target–CHF network was constructed. The IL6/JAK/STAT3 signaling pathway is likely critical to QLP's therapeutic effect on CHF. A CHF mouse model was established using aortic ligation surgery to investigate the regulation of the IL6/JAK/STAT3 pathway by QLP in CHF mice. Network pharmacology analysis and in vivo experimental data indicate that QLP alleviates myocardial injury and inflammatory response in CHF mice by modulating the IL6/JAK/STAT3 pathway, significantly improving cardiac function. This presents a promising therapeutic strategy for CHF treatment.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validated LC–MS/MS Method for the Determination of Paxalisib on Mouse Dried Blood Spots: An Application to Pharmacokinetic Study in Mice 经验证的LC-MS/MS法测定小鼠干血斑中Paxalisib的含量——在小鼠体内药动学研究中的应用。

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-02 DOI: 10.1002/bmc.6071

Ashok Zakkula, M. Akiful Haque

{"title":"Validated LC–MS/MS Method for the Determination of Paxalisib on Mouse Dried Blood Spots: An Application to Pharmacokinetic Study in Mice","authors":"Ashok Zakkula, M. Akiful Haque","doi":"10.1002/bmc.6071","DOIUrl":"10.1002/bmc.6071","url":null,"abstract":"<div>\u0000 \u0000 <p>Paxalisib is a dual PI3K/mTOR inhibitor, being used in advanced cancer treatment. In this research, we report a validated LC–MS/MS method for quantifying paxalisib from mouse dried blood spot (DBS). We validated the method in-line with the FDA guidelines. Liquid–liquid extraction technique was used to extract paxalisib from the DBS discs. We used a Chromolith RP-18 end cap (100 × 4.6 mm) column and isocratic mobile phase for the chromatographic separation of paxalisib and the internal standard (IS, dasatinib). The flow was 0.80 mL/min. In the optimized chromatographic conditions, the retention of paxalisib and the IS was ~2.13 and 2.06 min, respectively. Each injection total run time was 2.50 min. The MS/MS ion transitions monitored were <i>m/z</i> 383.2 → 309.1 and 488.1 → 410.1 for paxalisib and the IS, respectively. We have used a broad calibration range (1.24–3762 ng/mL) with a determination coefficient (<i>r</i><sup>2</sup>) of 0.995. All the validation parameters assessed met the acceptance criteria, and hematocrit had no effect on DBS Paxalisib concentrations. We have used the validated method to derive the intravenous and oral pharmacokinetic parameters by quantifying paxalisib in mouse blood and correlated with mice pharmacokinetic data.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920582","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 the Determination of Mobocertinib and Its Metabolite Desmethyl-Mobocertinib in Human Plasma and Its Application to Clinical Pharmacokinetic Study 简便灵敏的LC-MS/MS法测定人血浆中莫博塞替尼及其代谢物去甲基-莫博塞替尼及其在临床药动学研究中的应用

IF 1.8 4区医学

Biomedical Chromatography Pub Date : 2025-01-02 DOI: 10.1002/bmc.6063

Fan Tang, Xiaoli Hou, Jiajie Chen, Yasen Cao, Yixia Wang, Hong Cheng

{"title":"A Simple and Sensitive LC-MS/MS Method for the Determination of Mobocertinib and Its Metabolite Desmethyl-Mobocertinib in Human Plasma and Its Application to Clinical Pharmacokinetic Study","authors":"Fan Tang, Xiaoli Hou, Jiajie Chen, Yasen Cao, Yixia Wang, Hong Cheng","doi":"10.1002/bmc.6063","DOIUrl":"10.1002/bmc.6063","url":null,"abstract":"<div>\u0000 \u0000 <p>Mobocertinib is a potent selective tyrosine kinase inhibitor approved for the treatment of non–small cell lung cancer with activating EGFR exon 20 insertions. The aim of this study was to develop a procedure for liquid chromatography tandem mass spectrometry (LC-MS/MS) for the determination of mobocertinib and its metabolite desmethyl-mobocertinib in human plasma. The human plasma samples were precipitated with acetonitrile and analyzed using a Waters ACQUITY BEH C<sub>18</sub> column coupled to a triple quadrupole mass spectrometer. Separation was executed using the acetonitrile–0.1% formic acid solution with gradient elution, at a flow rate of 0.4 mL/min. Mobocertinib and desmethyl-mobocertinib were monitored by multiple reaction monitoring (MRM) with <i>m</i>/<i>z</i> 586.5 > 72.2 and 572.4 > 473.2, respectively. The procedure demonstrated excellent linearity (<i>r</i> > 0.997) within the concentration range of 0.1–200 ng/mL for both analytes. Precision in relative standard deviation was < 9.37% for mobocertinib and < 12.03% for desmethyl-mobocertinib. Accuracy in relative error was within −7.23% to 9.18% for mobocertinib and −2.78% to 9.87% for desmethyl-mobocertinib. Extraction recovery was > 80% for both analytes. The validated LC-MS/MS method was successfully applied to the pharmacokinetic study of mobocertinib and desmethyl-mobocertinib in healthy human volunteers with K<sub>2</sub>EDTA as anticoagulant after a single dose of mobocertinib (160 mg).</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920543","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