Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Nanostructured genosensor platform based on polypyrrole film and graphene quantum dots for the detection of high-risk HPV","authors":"Luiza G.T. Santos ,&nbsp;Alberto G. Silva-Junior ,&nbsp;Maurília P. Costa ,&nbsp;Karen Y.P.S. Avelino ,&nbsp;Norma Lucena-Silva ,&nbsp;Cesar A.S. Andrade ,&nbsp;Maria D.L. Oliveira","doi":"10.1016/j.jpba.2025.116920","DOIUrl":"10.1016/j.jpba.2025.116920","url":null,"abstract":"<div><div>Human Papillomavirus (HPV) is a globally prevalent infection that contributes to both benign and malignant diseases. While low-risk HPV types cause warts, high-risk strains are linked to cervical cancer and other malignancies. The most prevalent HPV subtypes, HPV 16 and 18, are accountable for over 70 % of cervical cancer cases globally. The virus poses a significant public health burden, particularly in low-resource settings. The electrochemical genosensor stands out as a promising tool for detecting and screening HPV and other cancer-related viruses. For this reason, we developed an electrochemical genosensor for the detection of high-risk HPV. A nanostructured electropolymerized polypyrrole (PPy) film and graphene quantum dots (GQD) were designed for the immobilization of the HPV MY09 probe. The sensing platform was characterized using cyclic voltammetry (CV) and atomic force microscopy (AFM) to evaluate biological samples of cDNA from infected patients. Topographical analysis revealed increased peaks and roughness regarding the hybridization process between the sensing platform and patient samples. Electrochemically, the proposed biosensor exhibited a sensitive response to recombinant plasmid and cDNA samples, revealing a limit of detection (LOD) of 0.62 pg/mL and 0.85 pg/mL for plasmid and cDNA samples, respectively. Moreover, the genosensor presented excellent selectivity over negative patient samples and interfering molecules. Therefore, our results highlight the ability of the PPy-GQD-MY09probe-BSA genosensor platform to detect different HPV genotypes, displaying a higher affinity for HPV 16 and 18. The developed sensor strategy stands out as a promising tool for HPV diagnosis and follow-up treatment.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116920"},"PeriodicalIF":3.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886867","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 electronic eye, electronic nose and high performance liquid chromatography for identification of raw and salt-processed Psoralea corylifolia fructus","authors":"Xingyu Zhu ,&nbsp;Wenhao Dong ,&nbsp;Yuwei Zhao ,&nbsp;Peng Chen ,&nbsp;Mingxuan Li ,&nbsp;Meihui Chen ,&nbsp;Weidong Li ,&nbsp;Chenghao Fei","doi":"10.1016/j.jpba.2025.116915","DOIUrl":"10.1016/j.jpba.2025.116915","url":null,"abstract":"<div><div><em>Psoralea corylifolia</em> fructus (PF), a traditional drug widespread use in China, is available in two forms: raw <em>Psoralea corylifolia</em> fructus (RPF) and salt-processed <em>Psoralea corylifolia</em> fructus. (SPF). Despite the distinct therapeutic efficacies of RPF and SPF, their morphological similarities pose a challenge for their rapid and accurate differentiation. To investigate the differences in color, volatile, and non-volatile compounds between RPF and SPF, and to develop a novel, rapid method for their differentiation. An integrated strategy combined electronic eye (E-eye), electronic nose (E-nose), and high-performance liquid chromatography (HPLC) was employed. E-eye was employed to quantify the visual color attributes. Concurrently, E-nose was used to analyze the odor profiles. The non-volatile compounds were identified using HPLC. Additionally, the practicality of these methods was evaluated using the Blue Applicability Grade Index (BAGI). Chemometric analysis was conducted to identify markers capable of distinguishing between RPF and SPF. The parameters <em>L</em>* and <em>b</em>* were selected as chromaticity markers. Additionally, 14 compounds, including 1-butanol, 1,2-dimethylbenzene, and β-pinene etc., were identified as volatile markers. The compounds bakuchiol and bavachin were identified as potential non-volatile markers. The performance scores for the E-eye, E-nose, and HPLC methods were 77.5, 80.0, and 72.5, respectively, suggesting their applicability. This study elucidated differences in color, volatile, and non-volatile compounds between RPF and SPF. It not only improves the quality control of PF but also introduces an innovative approach for the rapid differentiation of RPF and SPF.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116915"},"PeriodicalIF":3.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879447","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":"A thorough clinical study pipeline to discover and validate biomarkers in kidney transplantation: The European BIOMARGIN program","authors":"Pierre Marquet ,&nbsp;Antoine Humeau ,&nbsp;Dany Anglicheau ,&nbsp;Maarten Naesens ,&nbsp;Wilfried Gwinner ,&nbsp;Etienne A. Thevenot ,&nbsp;Marc Labriffe ,&nbsp;Marie Essig","doi":"10.1016/j.jpba.2025.116911","DOIUrl":"10.1016/j.jpba.2025.116911","url":null,"abstract":"<div><div>The European research program BIOMARGIN (Biomarkers of Renal Graft Injuries) seeks to identify and validate non-invasive biomarkers of graft lesions in kidney transplant patients. Graft biopsies represent the gold standard to identify graft lesions, but they are invasive, and their interpretation is subject to large inter-operator variability. Non-invasive biomarkers able to detect graft lesions early would help reduce or eliminate the use of biopsies and propose medical intervention earlier. BIOMARGIN entails a thorough clinical research pipeline for the untargeted discovery, selection and repeated validation of urine, blood and biopsy biomarkers (mRNAs, miRNAs, metabolites, peptides or proteins) of kidney graft rejection or interstitial fibrosis/tubular atrophy. It combines: (i) two case-control studies to identify, confirm and select the best biomarker signatures; (ii) a cross-sectional study to assess their diagnostic performance in a representative population; (iii) a longitudinal cohort study to evaluate their diagnostic and predictive performance in adult and pediatric patients; (iv) very thoroughly standardized and monitored sample collection, preparation, storage and shipment; (v) gold-standard outcomes through centralized, consensus histological assessment of graft biopsies; (vi) untargeted -omics techniques for the discovery, and targeted techniques for the quantitation, of candidate biomarkers; and (vii) a sophisticated statistical pipeline to select biomarker candidates (avoiding confounders), combine them with clinical data and evaluate their diagnostic and prognostic performances. More than 2500 biopsies, 4200 plasma and 9700 urine samples have been collected from &gt; 1300 patients. To the best of our knowledge, there has never been such a comprehensive research program for clinical biomarkers.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116911"},"PeriodicalIF":3.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894469","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":"Untargeted LC-MS/MS- based metabolomics profiling of colorectal cancer cell lines reveals potential hypoxia-associated biomarkers","authors":"Refat M. Nimer ,&nbsp;Sara Arjah ,&nbsp;Marya Obeidat ,&nbsp;Saied A. Jaradat ,&nbsp;Ruba A. Zenati ,&nbsp;Yasser Bustanji ,&nbsp;Mohammad H. Semreen ,&nbsp;Lina A. Dahabiyeh","doi":"10.1016/j.jpba.2025.116912","DOIUrl":"10.1016/j.jpba.2025.116912","url":null,"abstract":"<div><div>Colorectal cancer (CRC), a common cancer of the large intestine, is influenced by metabolic reprogramming due to hypoxia. Novel biomarkers may be identified through metabolomics. While many CRC studies have reported metabolomic profiling, the metabolic profile of CRC in the context of oxygen content has yet to be elucidated. Comprehending the metabolic alterations in cancer cells transitioning from normoxia (NMX) to hypoxia (HPX) and anoxia (ANX) is essential for the formulation of drugs that target particular metabolic pathways. Our study aimed to find metabolic changes in the HCT-116 CRC cell line under ANX, HPX, and NMX conditions, as well as to investigate novel biomarkers for CRC utilizing liquid chromatography-mass spectrometry (LC-MS/MS) based metabolomics approaches. Our findings showed significant changes in 77 metabolites in HCT-116 CRC cells across ANX, HPX, and NMX conditions, with 34 metabolites significantly disrupted in HPX compared to NMX, and 64 metabolites significantly changed in HPX compared to ANX. Significant differences included glutathione, gamma-glutamylcysteine, glycerophosphocholine, adenosine monophosphate, 5′-methylthioadenosine, guanosine 5′-diphosphate, threonic acid, and L-acetylcarnitine. Comprehending the metabolic changes in HPX, ANX, and NMX may uncover new pathways that could be targeted for potential treatments.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116912"},"PeriodicalIF":3.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883069","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":"Unveiling mitochondrial-targeting compounds in Qishenyiqi dropping pills for heart failure treatment: An integrative UHPLC-QTOF MS and high-content imaging strategy","authors":"Yishi Xie ,&nbsp;Xudong Xing ,&nbsp;Yixin Cui ,&nbsp;Yanwei Tan ,&nbsp;Xinyi Liang ,&nbsp;Hanlin Dai ,&nbsp;Miao Xu ,&nbsp;Yang Liu ,&nbsp;Fanxing Zhou ,&nbsp;Hua Yang ,&nbsp;Ping Li ,&nbsp;Haji Akber Aisa","doi":"10.1016/j.jpba.2025.116860","DOIUrl":"10.1016/j.jpba.2025.116860","url":null,"abstract":"<div><div>Mitochondrial dysfunction, a central pathogenic driver of heart failure (HF), underscores the therapeutic imperative to preserve mitochondrial homeostasis. Qishenyiqi dropping pills (QSYQ), a clinically validated traditional Chinese formulation, exhibits cardioprotective efficacy in HF; however, its mitochondrial-targeting bioactive constituents and mechanisms remain uncharacterized. Here, we integrate untargeted UHPLC-QTOF MS chemical profiling with high-content phenotypic screening across three HF cellular models—isoproterenol-induced hypertrophy, TGF-β1-driven fibrosis, and LPS-triggered inflammation—to systematically identify mitochondrial-targeting active compounds in QSYQ. Multidimensional assessment of mitochondrial function (ATP synthesis, membrane potential, reactive oxygen species flux) combined with machine learning-aided chemophenotypic mapping revealed 74 bioactive candidates from 2385 <em>m/z</em> signals, including novel HF-associated compounds. Crucially, pratensein-7-<em>O-β-D</em>-glucopyranoside (PG), a previously unreported isoflavone in QSYQ, demonstrated potent antifibrotic activity in NIH/3T3 cells via mitochondrial optimization: restoring ATP production, stabilizing membrane potential, and suppressing mtROS. This study establishes PG as a first-in-class mitochondrial homeostatic regulator within QSYQ, while advancing a phenotype-driven discovery framework that bridges traditional medicine complexity with mechanistic cardiology.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116860"},"PeriodicalIF":3.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883120","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":"Elucidation of the potential mechanism of Euphorbiae Pekinensis Radix and Glycyrrhizae Radix for the remission of ascites in hepatocellular carcinoma using a comprehensive strategy based on chinmedomics, pharmacology, and biopharmaceutics","authors":"Meiqi Liu ,&nbsp;Xiaoran Zhao ,&nbsp;Piaopiao Yang ,&nbsp;Zicheng Ma ,&nbsp;Yu Yin ,&nbsp;Guangjiao You ,&nbsp;Lili Sun ,&nbsp;Yanan Liu ,&nbsp;Xiaoliang Ren","doi":"10.1016/j.jpba.2025.116914","DOIUrl":"10.1016/j.jpba.2025.116914","url":null,"abstract":"<div><div>As recorded in Traditional Chinese medicine (TCM) theory, <em>Euphorbiae Pekinensis</em> Radix (EPR) and <em>Glycyrrhizae</em> Radix (GR) compose one herbal pair of the so-called “Eighteen Incompatible Medicaments”. The EPR-GR combination has displayed potential in the treatment of malignant ascites. However, the validity of this theory has been challenged due to insufficient evidence. In this study, the chemical substance responsible for the compatibility between GR and EPR was systematically analyzed by UPLC-Q-TOF-MS and chemical methods. SD rats were used to evaluate the toxicity of EPR and EPR-GR. Serum and several tissues were collected for biochemical analysis, histopathological examination, and chinmedomics. A mouse model of H22 HCC ascites was established to observe the therapeutic effects. The relationship between the expression of renal aquaporins (AQPs) and the therapeutic effect of EPR-GR on liver cancer ascites was investigated. Finally, the <em>in vitro</em> biopharmaceutical properties were investigated. The result showed that the contents of most of the chemical components in EPR tended to increase after pairing with GR, and the contents of the pairing markers increased significantly. Elevated blood levels of ellagic acid (EA) and decreased levels of 3,3′-di-O-methyl ellagic acid-4′-O-β-D-xylopyranoside (DEAX), and 3,3′-di-O-methyl ellagic acid (DEA), were observed after compounding GR with EPR. EPR can cause damage to intestinal tissues, and when combined with GR, it can cause slight damage to the liver and spleen. EPR can reduce body weight, waist circumference, and ascites volume in mice with liver cancer ascites and alleviate the symptoms of ascites in liver cancer. The therapeutic effect of the EPR-GR combination was better than EPR. The combined GR enhanced the down-regulation of AQP2 and AQP3. Molecular docking results confirmed that the blood components of EPR, EA, DEAX and DEA, could be stably bound to AQP2/AQP3 proteins. After compounding with GR and its components, the BCS classification of EPR was unchanged but shifted toward high solubility and low permeability. The findings indicate that GR-EPR could exhibit significant potential in mitigating ascites associated with hepatocellular carcinoma.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116914"},"PeriodicalIF":3.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869282","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":"Receptor-based bioassay for functional IL-2 quantification","authors":"Chuanwei Lu,&nbsp;Shuangshuang Xu,&nbsp;Xuelian Shan,&nbsp;Jiayu Wang,&nbsp;Xinyue Hu,&nbsp;Yuming Fang,&nbsp;Shanshan Wang,&nbsp;Grace Gong","doi":"10.1016/j.jpba.2025.116913","DOIUrl":"10.1016/j.jpba.2025.116913","url":null,"abstract":"<div><div>IL-2 is a potent cytokine that promotes multiple immune cells proliferation and activation. Accordingly, IL-2 based immunotherapies are emerging to treat cancers or AIDS by enhancing T cell growth and function. Besides, IL-2 is indispensable in in vitro cultivation of immune cells which is a critical step of CAR-T or CAR-NK immunotherapies. In bulk manufacturing of recombinant IL-2, <em>E. coli</em> expression system has several advantages such as low cost and rapid growth. However, high level protein expression in prokaryotic organisms often results in inactive insoluble aggregates, also known as inclusion bodies. It is crucial and most challenging work to solubilize and refold the protein of interest from inclusion bodies to generate its bioactive form. While multiple spectrum method had been applied to monitor the refolding process, the question of how to measure the refolding efficiency from the perspective of its biological function remained unaddressed. Here we present a receptor-based sandwich ELISA method to evaluate the bioactive product in samples and provide a guidance for manufacturing bioactive rhIL-2 (recombinant human IL-2) with prokaryotic expression system. Compared to traditional antibody-based ELISA method, this novel approach truly measures the presence of functional rhIL-2 and also potentially allows the detection of rhIL-2 variants with modifications like PEGylation as it doesn’t rely on the exact amino acid sequence.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116913"},"PeriodicalIF":3.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883067","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":"Identification of plasma biomarkers for non-invasive diagnosis of hepatitis B cirrhosis","authors":"Piao Hu ,&nbsp;Haifeng Miao ,&nbsp;Mei Li ,&nbsp;Ruxue Zhou ,&nbsp;Qinqin Lou ,&nbsp;Dezhen Wang ,&nbsp;Junli Gao ,&nbsp;Feng Guo","doi":"10.1016/j.jpba.2025.116909","DOIUrl":"10.1016/j.jpba.2025.116909","url":null,"abstract":"<div><div>Hepatitis B virus (HBV) infection represents a major public health challenge due to its potential progression to liver cirrhosis and hepatocellular carcinoma, underscoring the importance of early diagnosis for effective management. This study aimed to identify plasma biomarkers for the non-invasive diagnosis of hepatitis B cirrhosis (HBC). We employed quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry on plasma samples from 27 individuals, including 13 patients with HBC and 14 with chronic hepatitis B (CHB). Bioinformatics analysis of 963 identified proteins revealed 234 differential expressed proteins, comprising 115 upregulated and 119 downregulated proteins. Four candidate biomarkers—CHI3L1, IGFBP1, SHBG, and TIMP2—were subsequently selected and validated using ELISA in a cohort of 158 patients, all demonstrating elevated levels in HBC patients. The four-biomarker panel (4MP) demonstrated superior diagnostic performance, achieving an area under the curve (AUC) of 0.902 for distinguishing HBC from CHB. For differentiating decompensated HBC from CHB, the 4MP achieved an AUC of 0.993, with a sensitivity of 93.75 % and specificity of 98.73 %. Mostly, the 4MP also performed well in identifying severe HBC from non-severe HBC, achieving an AUC of 0.911, with a sensitivity of 81.25% and specificity of 93.65%. In conclusion, this study identifies four novel plasma biomarkers for HBC, highlighting their potential to enhance non-invasive diagnostic strategies for monitoring HBC progression.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116909"},"PeriodicalIF":3.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883070","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":"Evaluating the carcinogenic potential of trazodone hydrochloride via duplex DNA targeting: Molecular interaction, binding mechanism and affinity assessment via structural calculations","authors":"Palak Sharma ,&nbsp;Shweta Singh ,&nbsp;Priyanka Gopi ,&nbsp;Majji Sai Sudha Rani ,&nbsp;Pratik Singh ,&nbsp;Prateek Pandya ,&nbsp;Mohd Sajid Ali","doi":"10.1016/j.jpba.2025.116881","DOIUrl":"10.1016/j.jpba.2025.116881","url":null,"abstract":"<div><div>Trazodone Hydrochloride (TRZ) is a selective serotonin antagonist reuptake inhibitor (SARI) antidepressant that is widely prescribed to treat depression. In this study, we have observed that TRZ disturbs the duplex DNA structure around the binding site causing base flip in the major groove and disrupting sequence readout. TRZ binds in the minor groove, yet it disturbs the DNA structure significantly, causing problems in sequence readout. Therefore, it would be interesting to investigate the interaction between duplex DNA. DNA binding study was conducted using multi-spectroscopic methods coupled with molecular simulations. Fluorescence investigations revealed a static quenching mechanism between TRZ and CT-DNA with a moderate binding strength (2.7 ×10⁴ LM⁻¹ at 288 K, 1.1 ×10⁴ LM⁻¹ at 298 K, 5.2 ×10³ LM⁻¹ at 308 K). The thermodynamic parameters suggested that the complexation was spontaneous, enthalpy-driven (-69.006 kJ/mol), with an entropy of −0.168 kJ/mol and Gibbs free energy ranging between −18.93 to −16.03 kJ/mol. Complexation was primarily facilitated by the formation of hydrogen bonds and Van der Waals forces which corroborated by the MM/PBSA findings. Detailed assessment of the binding mode and interaction mechanism through Molecular Docking and Molecular Dynamics Simulations (150 ns) indicated TRZ's affinity for the minor groove of CT-DNA which was further validated experimentally through displacement study with the known minor groove binder, DAPI. CD spectroscopy of CT-DNA in the absence and presence of TRZ revealed minor variations in the negative and positive bands indicative of groove binding. The structural variations of TRZ observed during binding indicated minor conformational adjustments and repositioning, especially at piperazine and chlorophenyl ring, providing stable interactions in the form of stacking forces leading to better fit within the binding site, particularly within the AT region of the CT-DNA's minor groove. The findings from this study will enhance our understanding of the interaction between TRZ and CT-DNA, adding depth to existing knowledge in the field.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116881"},"PeriodicalIF":3.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879449","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 quantification of 21 antihypertensive and diuretic drugs in plasma by UPLC-MS/MS: Application to clinical and forensic cases","authors":"Coralie Boudin ,&nbsp;Amandine Faure ,&nbsp;Alexandre Behouche ,&nbsp;Olivier Ormezzano ,&nbsp;Hélène Eysseric-Guérin ,&nbsp;Françoise Stanke-Labesque ,&nbsp;François Paysant ,&nbsp;Virginie Scolan ,&nbsp;Théo Willeman","doi":"10.1016/j.jpba.2025.116910","DOIUrl":"10.1016/j.jpba.2025.116910","url":null,"abstract":"<div><div>Systemic arterial hypertension, affecting more than 1 billion people worldwide, necessitates widespread use of antihypertensive and diuretic medications. However, the potential toxicity related to exposure of these medications is not always fully understood, potentially leading to underestimates of deaths related to cardiovascular drugs. Additionally, the growing interest in monitoring adherence to antihypertensive medications necessitates the development of specific analytical methods suitable for both clinical and forensic applications. In this study, we developed a novel, high-throughput quantitative method for the simultaneous analysis of 21 antihypertensive and diuretic drugs mainly in human plasma using liquid chromatography with tandem mass spectrometry. This method has several advantages, including minimal sample volume requirement, a one-step sample preparation using an Ostro® plate, and a chromatographic run time of 7 min. The method was successfully validated on 11 criteria following the European Medicines Agency’s guidances. The method was successfully applied to authentic samples from 62 clinical cases and 76 post-mortem cases, with two cases of severe intoxications more precisely described. The first case describes an attempted suicide by candesartan (2558 ng/mL in plasma) combined with celiprolol (18 ng/mL) and amlodipine (161 ng/mL). The second case is a diuretic-contaminated dietary supplement poisoning with plasma concentrations of 40 ng/mL for furosemide and 36 ng/mL for hydrochlorothiazide. The authors present a simple, fast, and sensitive quantification method for the analysis of 21 antihypertensive and diuretic drugs, with concentration values reported in both living subjects and post-mortem cases to aid in the often-challenging interpretation of cardiotropic drug concentrations.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"263 ","pages":"Article 116910"},"PeriodicalIF":3.1,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864065","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}