Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Simultaneous determination of 13 representative saponins from the total saponins of Gynostemma pentaphyllum in rat plasma using LC-MS/MS for pharmacokinetic study","authors":"Lili Liu ,&nbsp;Yaping Huang ,&nbsp;Qingqing Wang ,&nbsp;Ziyuan Wang ,&nbsp;Ke Pan ,&nbsp;Jian Zhang ,&nbsp;Ying Peng ,&nbsp;Guangji Wang ,&nbsp;Zhiqi Yin ,&nbsp;Jianguo Sun","doi":"10.1016/j.jpba.2025.116970","DOIUrl":"10.1016/j.jpba.2025.116970","url":null,"abstract":"<div><div>As a plant with a rich history of medicinal and dietary use, <em>Gynostemma pentaphyllum</em> (Thunb.) Makino is predominantly characterized by the gypenosides. Contemporary research has demonstrated that these saponins possess significant hypolipidemic and hypoglycemic effects. This study focused on developing an LC-MS/MS approach to elucidate the pharmacokinetic profiles of 13 gypenosides in rat models. The separation was accomplished using a ZORBAX Eclipse Plus C18 column (2.1 mm × 100 mm, 1.8 µm). Detection was facilitated by employing positive electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. The analytical method was fully validated, including selectivity, linear response, measurement precision, analytical accuracy, extraction efficiency, matrix interference, and sample stability. The lower limit of quantification (LLOQ) for all compounds was 10 ng/mL, with each exhibiting a favorable linear relationship (r ≥ 0.9960). The precision, as measured by the relative standard deviation (RSD) for intra-day and inter-day variability, did not exceed 8.41 %. The accuracy, expressed as the relative error (RE), varied from −4.42–8.42 %. The recovery rate of the extraction process was between 92.02 % and 114.77 %, and no notable matrix effects were detected. The stability of the compounds was confirmed under four distinct storage conditions. Pharmacokinetic results indicated that all analytes displayed rapid absorption, prolonged retention, and slow elimination in rats, and exhibited nonlinear pharmacokinetics at low, medium, and high dosage levels. This study has established a quantification method for 13 gypenosides and successfully applied it to their pharmacokinetic studies in rats, providing a foundation for their further development and utilization.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116970"},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Qualitative and quantitative determination of SIPI-2011 and its two major metabolites in human plasma","authors":"Jie Fang ,&nbsp;Jiao Jing ,&nbsp;Guangyao Li ,&nbsp;Yongbin Wang ,&nbsp;Binjiang Zhao ,&nbsp;Yan Zhan ,&nbsp;Lei Zhou ,&nbsp;Ying Liu ,&nbsp;Wei Zhang ,&nbsp;Ni Peng ,&nbsp;Xiaoyan Chen","doi":"10.1016/j.jpba.2025.116958","DOIUrl":"10.1016/j.jpba.2025.116958","url":null,"abstract":"<div><div>SIPI-2011, a structural modification of isoquinoline alkaloid, is under investigation for treating arrhythmias. To characterize the safety and tolerability, the pharmacokinetics and metabolism of SIPI-2011 were investigated in humans. After an oral administration of 600 mg SIPI-2011, a total of 32 metabolites were detected in human plasma by UPLC-UV/Q-TOF mass spectrometry utilizing mass defect filter method. The principal biotransformation pathways included di-dehydrogenation (M8–1), dehydrogenation (M9–2), and oxidation and dehydrogenation (M10–4). Afterward, a sensitive LC-MS/MS method was developed to simultaneously determine SIPI-2011 and its two major metabolites M8–1 and M9–2 in human plasma. The isotopically labeled internal standards of the metabolites were obtained by incubating deuterated SIPI-2011 with rat liver homogenates. To achieve effective chromatographic retention and separation, three analytes were eluted on an XDB-phenyl column with alkaline mobile phase, and detected by multiple reaction monitoring (MRM) with positive electrospray ionization source. To reduce the interference from the isotope signals of M8–1 and M9–2 in the higher calibration point, [M+H+ 1]⁺ ions were selected as precursor ions of M9–2 and SIPI-2011 for MRM analysis. The assay was linear in the concentration range 15.0–3000 ng/mL for SIPI-2011, 0.500–100 ng/mL for M8–1 and 1.00–200 ng/mL for M9–2. The parameters of the method validation all met the acceptance criteria. The pharmacokinetic study indicated that SIPI-2011 was rapidly absorbed with a median T_max of 0.65 h and a terminal half-life of 15.4 h when healthy volunteers were administered a single dose of 300 mg SIPI-2011. And the plasma exposures of the two metabolites M8–1 and M9–2 were less than 10 % of that of the parent drug.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116958"},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid qualitative and quantitative analysis of etomidate and its structural analogs in blood by UPLC-MS/MS and application in six forensic cases","authors":"Xiaoyu Qian ,&nbsp;Liying Zhou ,&nbsp;Xin Wang ,&nbsp;Huosheng Qiang ,&nbsp;Jian Li ,&nbsp;Ping Xiang ,&nbsp;Hui Yan","doi":"10.1016/j.jpba.2025.116962","DOIUrl":"10.1016/j.jpba.2025.116962","url":null,"abstract":"<div><div>Etomidate and its structural analogs have been increasingly abused, posing significant risks to public safety. This study aimed to develop an ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of etomidate, metomidate, isopropoxate, propoxate, and etomidate acid in human blood. The method involved taking 1 mL of a blank blood sample, adding 3 µL of 100 ng/mL internal standard solution and 3 mL of diethyl ether, vortexing, centrifuging, and then drying and redissolving the supernatant for analysis. The correlation coefficient (r) values of the calibration curves for etomidate and its structural analogs in blood samples in the range of 0.1–10 ng/mL and etomidate acid in the range of 1–100 ng/mL were all greater than 0.999. The limit of detection (LOD) and limit of quantitation (LOQ) of etomidate and its structural analogs were 0.05 ng/mL and 0.1 ng/mL, respectively. The LOD and LOQ of etomidate acid were 0.5 ng/mL and 1 ng/mL, respectively. Precision, accuracy, recovery, matrix effect, and dilution integrity met the validation requirements. The method for quantitative analysis of etomidate and its structural analogs in blood samples was established and validated, enabling the separation of the isomers propoxate and isopropoxate. In addition, the method was successfully applied to six real blood samples in forensic cases.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116962"},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consistency between stir-frying Bombyx Batryticatus formula granules and traditional decoctions based on multi-component qualitative and quantitative analysis combined with GC-IMS and chemometrics","authors":"Tan Xue ,&nbsp;Qi Wang ,&nbsp;Panpan Zhang ,&nbsp;Yan Miao ,&nbsp;Jianing Sun ,&nbsp;Fengyu Dong ,&nbsp;Xinjing Gui ,&nbsp;Jing Yao ,&nbsp;Ruixin Liu","doi":"10.1016/j.jpba.2025.116971","DOIUrl":"10.1016/j.jpba.2025.116971","url":null,"abstract":"<div><div>This study investigates the consistency between the formula granule decoction of stir-fried Bombyx Batryticatus(JC-DGD) and its traditional decoction (JC-TD) counterpart, using roasted Bombyx Batryticatus as a representative example.First, used high-performance liquid chromatography (HPLC) to establish the fingerprints of JC-TD and JC-DGD from four manufacturers (A, B, C, and D) and assess their similarity. There was no significant difference between the two (<em>P</em> &gt; 0.05).Quantified five key index components, including uracil.Compared the protein and crude polysaccharide contents using the Coomassie Brilliant Blue and phenol-sulfuric acid methods. The mean total content of index components, proteins, and crude polysaccharides in 10 batches of JC-TD was set as 1. The contents of index components in different categories - JC-DGD-provincial standard(JC-DGD-PS), JC-DGD-enterprise standard(JC-DGD-ES), TD, DGD, and DGCM from manufacturers A, B, C, and D—were 1.23, 0.38, 1.00, 0.72, 1.28, 0.58, 0.45, and 0.27, respectively. The protein contents were 1.51, 0.46, 1.00, 0.88, 1.43, 0.93, 0.35, and 0.66, respectively. The crude polysaccharide contents was 9.01, 0.74, 1.00, 4.05, 10.57, 1.96, 0.38, and 1.77, respectively. We identified 32 differential volatile organic compounds, including fenugreek lactone, using GC-IMS. Then evaluated the anticonvulsant effects of JC-TD and JC-DGD using an acute convulsion mouse model induced by pentylenetetrazole. The results showed that JC-DGD-A &gt; JC-TD ≈ JC-DGD-B (<em>P</em> &gt; 0.05)) were superior to those of JC-DGD-C and JC-DGD-D (<em>P</em> &lt; 0.01). Finally, calculate the recommended equivalent ratio of Chinese medicine formula granules (DGCM). The manufacturers A, B, C, and D were adjusted from 1:3, 1:10, 1:10, and 1:11–1:4.54 ± 0.51, 1:5.24 ± 2.22 (JC-B3 without adjustment: 1:3.6), 1:5.17 ± 0.49, and 1:3.44 ± 0.59, respectively. The overall, and the consistency between the two was analyzed through correlation analysis, cluster analysis, and multi-index dimensionality reduction discriminant analysis.Comprehensive results indicated that the quality of JC-DGD-A was significantly higher than that of JC-TD, while JC-DGD-B exhibited similar quality to JC-TD. In contrast, the quality of JC-DGD-C and JC-DGD-D was significantly lower than that of JC-TD. To enhance product quality and ensure the scientific rationality of clinical applications, manufacturers must adhere to national and provincial standards for formula granule drugs.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116971"},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint multi-technology applications for etablishing quality evaluation model of Coptidis Rhizoma","authors":"Mengyuan Li ,&nbsp;Jinling Guo ,&nbsp;Yuanhao Zhang ,&nbsp;Jingwen Yao ,&nbsp;Jiaming Ge ,&nbsp;Chenlu Wu ,&nbsp;Jing Zhao ,&nbsp;Ming Liu","doi":"10.1016/j.jpba.2025.116952","DOIUrl":"10.1016/j.jpba.2025.116952","url":null,"abstract":"<div><div>Based on the pharmacodynamic components of Coptidis Rhizoma (CR) against oral squamous cell carcinoma (OSCC), the combination of chromatographic and spectroscopic techniques was used to achieve the rapid detection of CR quality, which provided a reference for the implementation of the quality detection method of CR oriented to the clinical efficacy. Firstly, the pharmacodynamic components of CR in the treatment of OSCC were studied by means of network pharmacology and molecular docking technology, and the pharmacodynamic components were screened and verified in vitro to screen out the key active components. Subsequently, the contents of key active ingredients of CR from different origins were detected and quantitative analysis models were established by a combination of high performance liquid chromatography (HPLC) and near infrared spectroscopy (NIR) techniques. The results showed that berberine and palmatine in CR had strong curative effect in the treatment of OSCC. Using berberine and palmatine as the key active ingredients, the content of the key active ingredients obtained by HPLC was used as the reference, and the prediction model of berberine and palmatine content was constructed by combining the NIR and partial least squares regression algorithm, and the model obtained a better prediction result with the correlation coefficients of R²_p of 0.9704 and 0.8793, respectively. This study screened the index components of CR against OSCC, and also demonstrated that NIR combined with chemometrics had the ability to quantitatively analyse the content of the components quickly, conveniently and accurately. This study is expected to be used for the simultaneous rapid detection of the anti-OSCC components in CR, which will provide a reference for the quality evaluation of CR raw herbs oriented to clinical efficacy.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116952"},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive study of degradation pathways and formation mechanism of major degradation impurities of gamithromycin active ingredient by UHPLC-HRMS and NMR","authors":"Nayanthara U. Dharmaratne,&nbsp;Abu M. Rustum","doi":"10.1016/j.jpba.2025.116969","DOIUrl":"10.1016/j.jpba.2025.116969","url":null,"abstract":"<div><div>Gamithromycin is a semi-synthetic antibacterial agent used for treating cattle bovine respiratory disease. This study was performed focusing on separating and identifying the degradation impurities of gamithromycin while elucidating its degradation mechanisms. A comprehensive forced degradation analysis was meticulously conducted on the gamithromycin drug substance following VICH/ICH guidelines under a range of stress conditions, including acid, base, oxidation (using H₂O₂ and K₂Cr₂O₇), thermal, and photolytic stress. The analytes were separated by ultra-high performance liquid chromatography using a gradient elution on an Agilent Poroshell HPH-C18 column (50 mm × 2.1 mm, 1.9 µm) at a temperature of 60 °C. The mobile phases employed were 10 mM aqueous NH₄HCO₃ as mobile phase-A and a mixture of acetonitrile and methanol (7:3, v/v) as mobile phase-B. This study identified six degradation and five additional process impurities in the gamithromycin drug substance using high-resolution mass spectrometry in conjunction with tandem mass spectrometry. For impurity 6, an additional investigation was performed using nuclear magnetic resonance spectroscopy to confirm its structure. Mechanisms for the formation of the degradation impurities were also proposed. These findings enhance the understanding of the stability characteristics of gamithromycin and would provide significant insights for the formulation of drug products that include this drug.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116969"},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics uncovers Rubus idaeus-mediated recovery of energy and arginine metabolism in liver injury","authors":"Yudan Xu ,&nbsp;Lei Zhang ,&nbsp;Tengteng Fu ,&nbsp;Xujin Yang,&nbsp;Enna Lan,&nbsp;Yuling Deng,&nbsp;Yi Tao","doi":"10.1016/j.jpba.2025.116955","DOIUrl":"10.1016/j.jpba.2025.116955","url":null,"abstract":"<div><div>The global incidence of acute liver injury continues to rise, posing a significant threat to public health. While both raw and processed <em>Rubus idaeus</em> Linnaeus (RI) demonstrate hepatoprotective properties, their mechanisms require further elucidation. This study employed UPLC-Q-TOF/MS-based serum metabolomics to delineate the distinct liver-protective mechanisms of raw and processed RI in a murine model of acute liver injury. Following ten days of intragastric administration with low, medium, and high doses of raw and processed RI extracts, mice received intraperitoneal injection of 50 % carbon tetrachloride in olive oil. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), as well as liver levels of superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyproline (Hyp), were measured via ELISA. Liver histopathology was examined using Hematoxylin and Eosin (HE), Masson, and Sirius Red staining. Treatment with both raw and processed RI significantly reduced serum AST, ALT, and ALP levels while decreasing hepatic MDA and Hyp content compared to the model group. Conversely, SOD activity showed marked elevation. Metabolomic profiling identified 39 significantly altered endogenous metabolites in the model group, with subsequent characterization of 22, 23, and 7 distinctive biomarkers in the raw, salt-processed, and wine-processed RI treatment groups, respectively. These biomarkers predominantly associated with energy metabolism and arginine metabolism. Furthermore, the phenolic and flavonoid compounds in RI, known for their anti-inflammatory and antioxidant properties, played a key role in mitigating liver damage induced by CCl₄. These findings provide strong evidence supporting the potential use of both raw and processed RI in the development of hepatoprotective health products.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116955"},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional metabolomics revealed pyroglutamic acid may play a key role in idiopathic pulmonary fibrosis","authors":"Yang Wen,&nbsp;Jia-hui Nie,&nbsp;Xue-mei Qin,&nbsp;Zhen-yu Li","doi":"10.1016/j.jpba.2025.116967","DOIUrl":"10.1016/j.jpba.2025.116967","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible respiratory disease with poor survival rates. Despite significant research efforts, IPF still lacks a curative treatment. Excessive epithelial-mesenchymal transition (EMT) contributes to approximately one-third of fibroblasts in pulmonary fibrosis and plays a critical role in IPF pathogenesis. Identifying factors that regulate EMT is essential for developing effective therapeutic strategies for IPF. In this study, functional metabolomics revealed significant alterations in multiple metabolites in transforming growth factor-beta 1 (TGF-β1)-induced A549 cells, with pyroglutamic acid and 5-oxoprolinase (OPLAH) being identified as the most critical factors. Cellular experiments demonstrated that pyroglutamic acid effectively inhibited TGF-β1-induced EMT in A549 cells. Mechanistically, pyroglutamic acid inhibited IPF by suppressing EMT through the inhibition of Smad2/3 expression in TGF-β1-induced A549 cells. Bioinformatics analysis further elucidated the pyroglutamate is a potential metabolite that inhibits EMT. In addition, this study is the first to highlight the pivotal role of pyroglutamic acid and OPLAH in regulating EMT in IPF, offering novel insights into the metabolic mechanisms involved in IPF inhibition and providing a foundation for developing innovative therapeutic approaches for IPF.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116967"},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic study of plasma and L1CAM-captured exosomal proteins in children with autism spectrum disorders","authors":"Huajie Zhang ,&nbsp;Zhiyuan Liang ,&nbsp;Hongbin Zhuang ,&nbsp;Mingxian Wang ,&nbsp;Yuhan Huang ,&nbsp;Xueshan Cao ,&nbsp;Haiyi Chen ,&nbsp;Liming Shen ,&nbsp;Chengyun Feng","doi":"10.1016/j.jpba.2025.116965","DOIUrl":"10.1016/j.jpba.2025.116965","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) has become a neurodevelopmental disorder that seriously endangers the health of infants and children. In order to explore the pathogenesis of the disease and search for early diagnostic biomarkers. In this study, plasma exosomes (PEs) and neural cell adhesion molecule L1 (L1CAM)-captured exosomes (LCEs) of ASD and controls were extracted and lysed to obtain proteins. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics were applied to investigate the differences in the expression of PEs and LCEs proteins between the two groups. Twenty-eight plasma exosomal differentially expressed proteins (DEPs) were identified, which were mainly associated with immunity, inflammation, complement and coagulation, and lipoprotein metabolism and transport. Twenty L1CAM-captured exosomal DEPs were identified, which were mainly involved in cytoskeleton, tight junctions, focal adhesion, and platelet-associated pathways. Meanwhile, our results suggested that processes or signaling pathways associated with the DEPs from plasma exosomes may be activated, whereas those associated with L1CAM-captured exosome may be inhibited. These processes or signaling pathways have been reported to be associated with ASD in previous studies. These DEPs have the potential to be diagnostic markers. This study provides new insights into disease mechanisms and diagnostic markers of ASD.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116965"},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LBA and LC-MS/MS based comprehensive bioanalytical methods for FDA018, a Trop-2 targeted antibody-drug conjugate","authors":"Minlu Cheng ,&nbsp;Xianjing Li ,&nbsp;Ya Li ,&nbsp;Yiya Wang ,&nbsp;Wenjia Li ,&nbsp;Shuai Wang ,&nbsp;Chang Shu ,&nbsp;Qinxin Song ,&nbsp;Li Ding","doi":"10.1016/j.jpba.2025.116964","DOIUrl":"10.1016/j.jpba.2025.116964","url":null,"abstract":"<div><div>Recently, the approval of Trop-2 targeted antibody drug conjugate (ADC) has changed the dilemma of patients with advanced triple-negative breast cancer who rely on chemotherapeutics to improve their survival. FDA018, an ADC consisting of an anti-Trop-2 antibody conjugated with a topoisomerase inhibitor SN-38 via an acid-cleavable linker, is currently being investigated in clinical trials. Based on the urgent demand to evaluate the clinical pharmacokinetics of FDA018, ligand binding assays (LBAs) for the determination of SN-38-conjugated antibody and total antibody and LC-MS/MS methods for the determination of the free SN-38, its metabolite SN-38G and total SN-38 were developed. The comparability and DAR sensitivity evaluation of the ELISA strategies for SN-38-conjugated antibody and total antibody were emphasized. The sensitivity of the LC-MS/MS method for the simultaneous determination of SN-38 and SN-38G reached 0.500 ng/mL and 0.250 ng/mL, respectively. An effective solution has been proposed for the optical instability of the cleavable linker of FDA018 during the pretreatment process of biological samples. The established bioanalytical methods were comprehensively validated and the results satisfied the acceptable criteria of ICH M10. The validated bioanalytical methods have been applied to the single-dose pharmacokinetic study of FDA018 in patients with Trop-2-positive malignant tumors successfully, and the pharmacokinetic profiles of FDA018 and its constituent components were investigated.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"264 ","pages":"Article 116964"},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}