Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Integrating UPLC-Q-TOF-MS, network pharmacology, molecular docking, and molecular dynamics simulation to reveal the material basis and mechanism of Xiangshao sanjie oral liquid in treating hyperplasia of mammary glands","authors":"Jiaming Li ,&nbsp;Yu Zhang ,&nbsp;Dan Peng ,&nbsp;Lining Jiang ,&nbsp;Jingjing Wang ,&nbsp;Rui Ni ,&nbsp;Fang Liu ,&nbsp;Hongjun Xie ,&nbsp;Yao Liu","doi":"10.1016/j.jpba.2025.117074","DOIUrl":"10.1016/j.jpba.2025.117074","url":null,"abstract":"<div><div>Xiangshao sanjie oral liquid (XSSJ), a classical traditional Chinese medicine (TCM), has been applied to treat hyperplasia of the mammary gland (HMG) for more than 20 years in China. Whereas its active ingredients and pharmacological mechanisms remained unclear. This paper aims to elucidate the active ingredients in XSSJ and to provide a clear understanding of how these compounds interact with biological pathways and contribute to therapeutic outcomes. This study systematically identified 88 chemical constituents in XSSJ using UPLC-Q-TOF-MS, among which 22 potential active ingredients were screened based on oral bioavailability (OB) and drug-likeness (DL). In a rat HMG model, XSSJ treatment dose-dependently ameliorated mammary hyperplasia, as evidenced by reduced nipple height and diameter, normalized lobular structure, and volume of mammary acinus via histopathological evaluation. The serum levels of IL-1β, IL-6, and TNF-α were significantly decreased compared with the HMG rats. Furthermore, compared with the HMG model group, XSSJ significantly inhibited the levels of p-JNK/JNK, p-ERK/ERK, and p-P38/P38, and decreased the expression of NF-κB, COX-2, and iNOS in mammary gland tissue. Molecular docking and 200 ns molecular dynamics simulations were employed to evaluate stable binding conformations and robust interactions between active ingredients and key targets, and the results confirmed that these ingredient-target complexes exhibited excellent binding properties. These integrated findings demonstrated that the mechanism of XSSJ against HMG was related to MAPK/NF-κB signaling pathway, which could provide valuable experimental evidence and new perspectives to explore the potential mechanisms of XSSJ in treating HMG.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117074"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738815","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 assessments of pharmacokinetics and immunogenicity of farletuzumab ecteribulin, a novel antibody-drug conjugate against tumors expressing folate receptor α, in monkeys","authors":"Shawn Fernando ,&nbsp;Yuji Mano","doi":"10.1016/j.jpba.2025.117084","DOIUrl":"10.1016/j.jpba.2025.117084","url":null,"abstract":"<div><div>Farletuzumab ecteribulin (MORAb-202) is a novel antibody-drug conjugate (ADC) comprising farletuzumab and eribulin with a cathepsin-B cleavable linker, currently under development for tumors expressing folate receptor α. It is crucial to comprehend the pharmacokinetics (PK) of MORAb-202 in monkeys to enhance the accuracy of PK prediction in humans. To this end, a series of assays were devised for the total antibody (Tab) as the sum of conjugated and unconjugated antibodies, the conjugated antibody as the ADC, and the unconjugated eribulin (payload) by a ligand binding assay (LBA) and liquid chromatography with tandem mass spectrometry. The LBA by Gyrolab was employed for the quantification of Tab and ADC. Additionally, a semi-quantitative assay for anti-drug antibody (ADA) was developed using the LBA for the immunogenicity assessment. The quantifiable range for ADC and Tab in monkey serum was from 0.4 and 4 µg/mL, respectively, while eribulin was quantified from 0.2 ng/mL. The aforementioned methodologies were subsequently validated and employed in a PK study in monkeys. The accuracy and precision of the assay were within the criteria. Following intravenous administration, the PK profiles of Tab and ADC were similar, while minimal levels of eribulin. No ADA against MORAb-202 was detected in postdose samples.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117084"},"PeriodicalIF":3.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749074","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":"Application of metabolomics and MCDM approach in developing a novel strategy for disease diagnosis: A case study in Primary Sjögren's Syndrome","authors":"Ting Cui ,&nbsp;Nan Wang ,&nbsp;Lili Shang ,&nbsp;Jing Luo ,&nbsp;Zhenyu Li","doi":"10.1016/j.jpba.2025.117080","DOIUrl":"10.1016/j.jpba.2025.117080","url":null,"abstract":"<div><div>Primary Sjögren's Syndrome (pSS) is a complex autoimmune disease with an unclear etiology. Due to the lack of a single diagnostic gold standard, multidisciplinary and invasive examinations are often required for pSS, underscoring the urgent need for innovative non-invasive approaches to simplify the diagnostic process. Leveraging advances in machine learning and metabolomics, this study developed a novel diagnostic strategy using fecal non-targeted metabolomics data from 93 pSS patients and 42 healthy controls acquired via liquid chromatography-mass spectrometry (LC-MS). Through rigorous feature optimization with Shapley additive explanations (SHAP) and multi-criteria decision-making (MCDM), 10 pivotal differential metabolites were identified from 151 metabolites. A stacking ensemble framework integrating six machine learning models achieved exceptional diagnostic performance (AUC: 0.98, sensitivity: 0.97, specificity: 0.90, recall: 0.93, accuracy: 0.95), surpassing individual model outputs. A user-friendly visualized metabolic diagnostic system was concurrently established to enhance clinical application. These findings demonstrate that integrating machine learning into metabolomics research provides a robust, non-invasive solution for pSS diagnosis, with high generalizability and clinical applicability. This integrative approach not only addresses critical diagnostic challenges in pSS but also establishes a methodological paradigm for exploring metabolic biomarkers in other complex diseases.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117080"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724201","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":"Origin-dependent metabolic variations: How Atractylodes macrocephalae Rhizoma extract’s chemical diversity leads to stage-specific changes in simulated digestion","authors":"Hangming Li ,&nbsp;Lue Hong ,&nbsp;Yijun Wang ,&nbsp;Shuo Chai ,&nbsp;Ping Huang ,&nbsp;Hongmei Chen ,&nbsp;Wenhong Liu ,&nbsp;Wei Zhu ,&nbsp;Massimo Marzorati ,&nbsp;Hui Wang ,&nbsp;Jingkui Tian ,&nbsp;Xiaoyong Zhang","doi":"10.1016/j.jpba.2025.117082","DOIUrl":"10.1016/j.jpba.2025.117082","url":null,"abstract":"<div><div><em>Atractylodes macrocephalae</em> Rhizoma (AMR), a traditional Chinese medicine, is extensively utilized in clinical practice for its pharmacological properties, including anti-inflammatory, anti-tumor, and gastrointestinal regulatory effects. Nonetheless, the intricate nature of traditional Chinese medicine extracts has resulted in few studies into the effects of compositional variations in <em>Atractylodes macrocephalae</em> Rhizoma extracts (AMRE) from diverse sources on gastrointestinal metabolic processes. This study developed an integrated <em>in vitro</em> and <em>in vivo</em> compound analysis strategy utilizing Ultrahigh-performance liquid chromatography Quadrupole-Orbitrap tandem mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) and the Simulator of Human Intestinal Microbial Ecosystem (SHIME) to examine the metabolic alterations caused by variations in the chemical constituents of AMRE from diverse sources. A total of 117 chemical constituents were found, primarily classified as terpenoids, organic acids, alkaloids, coumarins, and phenylpropanoids. 51 prototype components and 79 metabolites were identified. The metabolic processes were predominantly observed among terpenoids, with reaction types encompassing hydroxylation, oxidation, hydrogenation, methylation, glucuronidation, and sulfonation. Analysis of dynamic changes revealed that the majority of the prototype components underwent a considerable reduction in the colon, while the metabolites were markedly enriched in both the small intestine and colon. Differential analysis showed that AMRE3 contained the highest number of terpenoid compounds, AMRE1 exhibited the highest average content of chemical constituents, and AMRE2 had the lowest. These disparities were consistently observed in both prototype components and metabolic behaviors, thereby affirming the robust correlation between metabolite distribution and chemical constituents. This study elucidates, for the first time, the variations in the chemical constituents of AMRE from diverse sources and the metabolic characteristics and discrepancies they elicit in the human gastrointestinal tract (GI tract), offering a viable strategy for further clarifying the material basis of its pharmacological effects and clinical applications.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117082"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749073","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":"Unraveling the plasma dynamics, oxidative metabolism and excretion behavior of M-PEG6-OH by UPLC-MS/MS","authors":"Yingxia Guo ,&nbsp;Jiaxin Zhang ,&nbsp;Runran Mei ,&nbsp;Zihan Tang ,&nbsp;Meichen Liu ,&nbsp;Xixian Weng ,&nbsp;Meiyun Shi ,&nbsp;Lei Yin","doi":"10.1016/j.jpba.2025.117083","DOIUrl":"10.1016/j.jpba.2025.117083","url":null,"abstract":"<div><div>Addressing critical gaps in understanding the <em>in vivo</em> behavior of polyethylene glycol (PEG)-based excipients, this study systematically elucidates the biological fate of methoxy-PEG₆-hydroxyl (M-PEG₆-OH) through comprehensive pharmacokinetic and metabolic investigations in rats. Employing a validated ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methodology, we reveal distinctive biodistribution characteristics including rapid systemic clearance (Half-life (t_1/2) = 1.92 ± 1.16 h) and extensive tissue penetration (Apparent volume of distribution (V_d) = 0.84 ± 0.45 L/kg), suggesting efficient extravascular dissemination. Excretion pathways analysis demonstrated predominant renal elimination, with 59.03 % of the administered dose recovered in urine within 48 h post-IV injection, contrasting with minimal fecal excretion (0.99 %). Quantitative metabolite profiling identified M-PEG₅-CH₂COOH as the oxidative transformation product through terminal hydroxyl modification. The significantly higher relative abundance of metabolites (M-PEG₅-CH₂COOH) in urine compared to feces within the same time period provides critical insights into the biotransformation processes and metabolic pathways of the PEG polymer. These findings establish the first systematic evidence of metabolic trajectory and elimination mechanisms for M-PEG-OH, offering vital references for optimizing PEGylated drug delivery systems with enhanced biocompatibility and predictable safety profiles.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117083"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724200","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":"Determining carbon-carbon double bond position of unsaturated glycerophospholipids in human plasma NIST® SRM® 1950 by electron impact excitation of ions from organics-tandem mass spectrometry (EIEIO-MS/MS)","authors":"Sara Martínez ,&nbsp;Ana Gradillas ,&nbsp;Hana Cermakova ,&nbsp;Michael Witting ,&nbsp;Coral Barbas","doi":"10.1016/j.jpba.2025.117081","DOIUrl":"10.1016/j.jpba.2025.117081","url":null,"abstract":"<div><div>Understanding the structural diversity and biological functions of unsaturated fatty acyl chains (FAC) esterified in complex lipids –such as glycerolipids (GL), glycerophospholipids (GP) or sphingolipids (SP)– requires precise knowledge of the degree of unsaturation, location, and geometrical isomerism of the carbon-carbon double bonds (C<img>C). However, the complex isomeric nature of lipids, combined with the inherent limitations of conventional tandem mass spectrometry (MS/MS) in structural elucidation, remains a major challenge in accurate C<img>C elucidation. To overcome this, advanced MS/MS strategies, such as electron impact excitation of ions from organics (EIEIO) have emerged, generating diagnostic fragment ions that enable unambiguous C<img>C localization. In the present study, we conducted a qualitative structural analysis of the C<img>C positions in esterified FAC of GP present in NIST® Human Plasma Standard Reference Material, SRM 1950, employing RP-UHPLC-ESI(+)-EIEIO-QTOF-MS/MS. Interpretation of ESI(+)-EIEIO-MS/MS spectra enabled C<img>C determination in 120 unsaturated GP, revealing a predominance of ω-6 and ω-3 FAC. These results offer new insights into the FAC distribution of this reference material, enhancing the structural annotation confidence level. By integrating such detailed molecular information, EIEIO-MS/MS proves to be a powerful approach for in-depth lipid structural elucidation in complex biological matrices, thereby contributing to methodological advancements and supporting its future application in translational lipidomics.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117081"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711007","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":"Molecular insights into the anti-asthma potential of Zhimu-Chuanbeimu drug pair based on serum pharmacochemistry, network pharmacology and immune infiltration analysis","authors":"Chunli Zhang ,&nbsp;Xi Tian ,&nbsp;Huiyi Zhang ,&nbsp;Jinhuan Wei ,&nbsp;Qingfei Cui ,&nbsp;Yiqi Xing ,&nbsp;Mengxin Yang ,&nbsp;Wenyu Li ,&nbsp;Jiayi Wang ,&nbsp;Xueyi Chen ,&nbsp;Yingfeng Du ,&nbsp;Yiran Jin","doi":"10.1016/j.jpba.2025.117077","DOIUrl":"10.1016/j.jpba.2025.117077","url":null,"abstract":"<div><div>In traditional Chinese Medicine, Zhimu-Chuanbeimu (ZC) is one of the most classical herb pairs used in the treatment of lung diseases such as asthma. This study aimed to elucidate its specific components and potential mechanisms involved in treating asthma by altering the immune microenvironment. A systematic analysis of the chemical substance and absorbent components were conducted using UHPLC-Q-TOF-MS. Subsequently, a targeted network pharmacology based on serum pharmacochemistry was employed to predict core targets and key active ingredients. By combining microarray data analysis and gene set enrichment analysis, key targets and immune environment changes were further clarified. Ultimately, the prediction mechanism was validated through molecular docking, molecular dynamic simulations, and <em>in vivo</em> experiment validation. Consequently, sixty-seven prototype substances were identified in the blood samples of normal rats. Through network pharmacology and microarray data analysis, CCND1 and ESR1 were selected as key targets. Gene set enrichment analysis indicated that the expression of CCND1 was correlated with T helper cells, while the expression of ESR1 was positively correlated with mast cells. Additionally, the molecular docking and molecular dynamic simulations effectively supported the binding affinity between puqienine C and markogenin with the binding pockets of CCND1 and ESR1. Finally, <em>in vivo</em> experiments revealed that ZC extract could improve airway hyperresponsiveness, pulmonary inflammatory infiltration, the expression of CCND1/ESR1 and Th1/Th2/Th17/Treg imbalance in OVA-induced asthma rats. In conclusion, this research uncovered the pharmacodynamic foundation of ZC and its potential multifaceted pharmacological impacts, indicating that its potential anti-asthma mechanism might involve the modulation of immune cells and associated inflammatory pathways. Moreover, it provided a benchmark for enhancing asthma treatment protocols.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117077"},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703036","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":"Formulation insights into competitive binding of N6-cyclohexyladenosine and 8-(p-sulfophenyl)theophylline with hydroxypropyl-β-cyclodextrin","authors":"Seungil Cho ,&nbsp;Carl Murphy ,&nbsp;Thomas Green ,&nbsp;Kelly Drew","doi":"10.1016/j.jpba.2025.117079","DOIUrl":"10.1016/j.jpba.2025.117079","url":null,"abstract":"<div><div>This study investigates the molecular interactions and physicochemical properties of N⁶-cyclohexyladenosine (CHA), a neuroprotective adenosine A1 receptor agonist, and 8-(p-sulfophenyl)theophylline (8-SPT), a co-administered non-selective adenosine receptor antagonist with limited blood-brain barrier permeability, and 2-hydroxypropyl-β-cyclodextrin (HPβCD), which serves as an excipient. The aim is to systematically evaluate how inclusion complexation with HPβCD affects the solubility and compatibility of drugs in combined formulations, using binding constant analysis to guide the investigation. Two analytical approaches were employed to determine the binding affinities of CHA and 8-SPT: capillary electrophoresis (CE) with UV/Vis absorption detection and nuclear magnetic resonance (NMR) spectroscopy. CE method development utilized two distinct buffers: phosphate buffer (pH 2.5) for protonated CHA and acetate buffer (pH 4.6) for 8-SPT. The detection limits were 2.0 ± 1.0 µg/mL (6 ± 3 µM) at 270 nm for CHA and 2.0 ± 1.0 µg/mL (6 ± 3 µM) at 210 nm for 8-SPT. CE analysis revealed apparent and average binding constants of 136 ± 13 M⁻¹ for protonated CHA and 121 ± 19 M⁻¹ for 8-SPT. NMR spectroscopy established the solubility profile of CHA in water and determined an apparent and average binding constant of 308 ± 30 M⁻¹ for neutral CHA. The relatively small binding constants suggest that 8-SPT does not significantly impact CHA solubility, stability, or availability in combined drug formulations, ensuring sufficient drug availability upon infusion into the bloodstream. These competitive binding constant studies provide valuable guidance for predicting drug solubility and compatibility in combined formulations.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117079"},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721394","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":"Integrated proteomics and metabolomics analysis of liver tissue reveal the therapeutic effect of Jiedu Huayu Granules on acute liver failure in rats","authors":"Zhipeng Wu ,&nbsp;Yuqin Zhang ,&nbsp;Dewen Mao ,&nbsp;Na Wang ,&nbsp;Zhengfeng Lu ,&nbsp;Huiping Yan ,&nbsp;Yanmei Lan ,&nbsp;Minggang Wang ,&nbsp;Rongzhen Zhang ,&nbsp;Mengru Peng ,&nbsp;Guoyuan Zeng","doi":"10.1016/j.jpba.2025.117072","DOIUrl":"10.1016/j.jpba.2025.117072","url":null,"abstract":"<div><div>This study aims to reveal the regulatory mechanism underlying the antagonistic effects of JDHY granules against ALF. The anti-inflammatory effect of JDHY granules was evaluated by observing hematoxylin-eosin staining of liver tissue sections and measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) in rats. Label-free quantitative proteomics and untargeted metabolomics were employed to assess protein and metabolite changes in liver tissues before and after JDHY treatment in ALF rats. Differentially expressed proteins (DEPs) and metabolites (DEMs) were identified and analyzed bioinformatically. JDHY granules alleviate the pathological changes in liver tissue, reduce the levels of serum ALT, AST, and TBIL in ALF rats. Proteomic results suggested that there were 303 DEPs in model group and the JDHY granule group, which were enriched in pathways such as the PI3K-Akt signaling pathway, glycolysis, and gluconeogenesis. Metabolomic analysis identified 31 DEMs between the model and JDHY granule groups. These metabolites were enriched in pathways such as glycolysis and gluconeogenesis. Joint enrichment analysis of proteomics and metabolomics revealed significant enrichment of DEPs and metabolites DEMs in pathways such as glycolysis and gluconeogenesis. Moreover, parallel reaction monitoring validated the parallel changes of common DEPs in ALF liver, exhibiting consistent expression changes as observed in the proteomic analysis. The therapeutic efficacy of JDHY granules in ALF may involve PI3K-AKT pathway activation and inhibition of liver glycolysis, thereby alleviating hepatic inflammatory stress.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117072"},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721395","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":"LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib","authors":"Marinda Meertens ,&nbsp;L. Daniëlle de Jong ,&nbsp;Niels de Vries ,&nbsp;Hilde Rosing ,&nbsp;Jos H. Beijnen ,&nbsp;Alwin D.R. Huitema","doi":"10.1016/j.jpba.2025.117078","DOIUrl":"10.1016/j.jpba.2025.117078","url":null,"abstract":"<div><div>A reversed-phase liquid chromatography-tandem mass spectrometry method was developed and validated for quantifying nine novel oral targeted anticancer agents mainly indicated for non-small cell lung cancer: adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib in human plasma for therapeutic drug monitoring. Chromatographic separation used an Acquity BEH C18 column with step gradient of 0.1 % formic acid in water and acetonitrile-methanol (50:50, v/v), at a 0.5 mL/min flow rate. Plasma samples were pretreated via precipitation with acetonitrile and diluted in 0.1 % formic acid in water. The reversed-phase chromatography was coupled with tandem mass spectrometry in positive ion mode. The assay was successfully validated over the following ranges: 100 – 10,000 ng/mL for adagrasib, capmatinib, entrectinib, pralsetinib, selpercatinib; 50 – 50,000 ng/mL for ensartinib; 10 – 1000 ng/mL for larotrectinib, lorlatinib; and 10 – 10,000 ng/mL for sotorasib. Accuracy and precision met the predefined criteria. Stability tests confirmed that all analytes were stable in plasma for up to 157 days at −20°C except for entrectinib, which was stable for 35 days at −20°C. At room temperature, the analytes were at least stable in plasma for 7 days, however, for adagrasib, entrectinib and sotorasib, stability for up to 3 days could be demonstrated. We recommend sending these samples on dry ice or refrigerated. After the validation, 74 plasma samples were measured in the application phase and all results but one fell within the validated ranges. This assay allows simultaneous quantification of nine novel targeted therapies and supports therapeutic drug monitoring.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117078"},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724213","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}