Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Chemometric tools to comprehend a recovery process for the bioactive ingredients from purple basil (Ocimum basilicum L.): Box-Behnken design-based optimization and principal component analysis","authors":"İrem Toprakçı,&nbsp;Ebru Kurtulbaş,&nbsp;Selin Şahin","doi":"10.1016/j.jpba.2025.116676","DOIUrl":"10.1016/j.jpba.2025.116676","url":null,"abstract":"<div><div>Medicinal and aromatic plants are alternative products to synthetics because of their antioxidant, antimicrobial, anti-inflammatory and antidiabetic effects. The objective of this study is to investigate the automated solvent extraction (ASE) process parameters for the extraction of bioactive-rich substances from purple basil (<em>Ocimum basilicum</em> L.). Process optimization in relation to total phenolic content (TPC), total flavonoid content (TFC), and total anthocyanin content (TAC) was performed through a chemometric approach. The ASE system was designed, modelled and optimized by 3-factor and 3-level Box-Behnken design of Response Surface method (RSM). Antioxidant activity of the samples were measured by 2 different free radical scavenging activity assays (ABTS and DPPH). By using principal component analysis (PCA) to the dataset, the impact of interactions between the parameters was also evaluated according to their antioxidant activity, TPC, TFC and TAC levels. The optimal ASE conditions (0.3 g of purple basil, 19 min of immersion time and 66 % ethanol solution) provided the highest yields of TPC (98.888 mg-GAE/g-DM), TFC (27.033 mg-CE/g-DM) and TAC (11.556 mg-C3G/g-DM), which were verified by satisfactory validation findings (the error&lt;2 %).</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116676"},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039549","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":"Peptide mapping analysis of synthetic semaglutide and liraglutide for generic development of drugs originating from recombinant DNA technology","authors":"Soo Hyun Kim ,&nbsp;Sung Soo Kim ,&nbsp;Hyun Jun Kim ,&nbsp;Eun Ji Park ,&nbsp;Dong Hee Na","doi":"10.1016/j.jpba.2025.116682","DOIUrl":"10.1016/j.jpba.2025.116682","url":null,"abstract":"<div><div>Semaglutide and liraglutide are long-acting glucagon-like peptide-1 receptor agonists used to treat type-2 diabetes and obesity. Recent advances in peptide synthesis and analytical technologies have enabled the development of synthetic generic peptide for reference listed drugs (RLD) originating from recombinant DNA (rDNA) technology. Since the original semaglutide and liraglutide were produced through rDNA technology, there has been great interest in developing their synthetic peptides as generic versions of the original drugs. Therefore, this study aimed to develop a peptide mapping method to describe the primary structure of semaglutide and liraglutide using ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS), and to apply this method to demonstrate the sameness between synthetic peptides for generic drugs and rDNA peptides of the original drugs. Masses of the peptide fragments were identified using HRMS at an accurate level of mass error below 10 ppm, and their sequences were determined via MS^E sequencing using in-source fragmentation, which was also useful for identifying the fatty acid chain modification site. Full sequence coverage of each semaglutide and liraglutide was accomplished by combining peptide maps generated using Glu-C and chymotrypsin. The proposed peptide mapping method using UPLC-HRMS was useful for determining active ingredient sameness between generic synthetic peptides and previously approved peptide drug products of rDNA origin.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116682"},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028896","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":"Ganoderma lucidum spore oil attenuates acute liver injury by modulating lipid metabolism and gut microbiota","authors":"Jianying Liu ,&nbsp;Yan Chen ,&nbsp;Zhifeng Cen ,&nbsp;Meiqi Hong ,&nbsp;Binzhi Zhang ,&nbsp;Xia Luo ,&nbsp;Leqi Wang ,&nbsp;Shasha Li ,&nbsp;Xue Xiao ,&nbsp;Qinqiang Long","doi":"10.1016/j.jpba.2025.116674","DOIUrl":"10.1016/j.jpba.2025.116674","url":null,"abstract":"<div><div>The incidence of acute liver injury is increasing and poses a significant threat to human health. <em>Ganoderma lucidum</em> spore oil (GLSO), a lipid substance extracted from <em>Ganoderma lucidum</em> spore powder using supercritical CO₂ technology, has been investigated for its potential to prevent acute liver injury. However, the specific mechanism underlying the protective effects of GLSO remains incompletely understood. In this study, we investigated the preventive effect of GLSO on acute liver injury in rats, focusing on the gut microbiome and serum metabolomics. GLSO effectively alleviated liver dysfunction and reduced inflammation, leading to the prevention of acute liver injury in rats. Serum metabolomics analysis revealed that GLSO primarily modulated lipid metabolic pathways related to glycerophospholipid metabolism and sphingolipid metabolism. Specifically, GLSO decreased the levels of metabolites such as lysophosphatidylcholine (LPC), glycerophosphatidylcholine (GPC), and sphinganine 1-phosphate (SA1P), while increasing the levels of phosphatidylglycerol (PG) and digalactosylceramide (DGC). Gut microbiomics data indicated that GLSO effectively regulated the composition of the gut microbiota in rats with acute liver injury. Specifically, it increased the abundance of <em>Firmicutes</em> and decreased the abundance of <em>Proteobacteria</em>. Mantel test correlation analysis revealed a close relationship between gut microbial <em>Burkholderiales</em> and lipid metabolites in GLSO-mediated prevention of acute liver injury. GLSO exerts its preventive effects on acute liver injury by remodeling the gut microbiota and regulating lipid metabolism. These findings provide novel insights and potential directions for the development of new drugs targeting acute liver injury.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116674"},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022966","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 based analytical strategies for the detection of lipid peroxidation products in biological matrices","authors":"Federico Fanti ,&nbsp;Manuel Sergi ,&nbsp;Dario Compagnone","doi":"10.1016/j.jpba.2025.116681","DOIUrl":"10.1016/j.jpba.2025.116681","url":null,"abstract":"<div><div>Oxidative stress (OS) arises mainly from exposure to reactive oxygen species (ROS) such as superoxide anion, hydroxyl radical, and hydrogen peroxide. These molecules can cause significant damage to proteins, DNA, and lipids, leading to various diseases. Cells fight ROS with detoxifying enzymes; however, an imbalance can cause damage leading to ischemic conditions, heart disease progression, and neurological disorders such as Alzheimer's disease. Accurate assessment of OS levels is then crucial and oxidized lipidic products are considered relevant OS biomarkers. In fact, lipids are particularly prone to ROS attack, leading to lipid peroxidation, cell membrane damage, and toxic by-products affecting DNA, proteins, and low-density lipoproteins. This review reports on recent advances in LC-MS/MS approaches for OS lipidic biomarkers, focusing on overcoming analytical challenges. 3 different classes of biomarkers have been reported, malondialdehyde, isoprostanes and oxidised sterols. For each class, the main analytical challenges with a particular focus on derivatisation procedure, sensitivity, matrix effect, ionisation have been described and discussed. The recent advancements of the LC-MS-MS procedures move towards simpler approaches, reducing errors and improving the reliability of the measurement thus enabling a comprehensive and robust OS assessment.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116681"},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-zirconium-silicate solid-phase extraction method for the rapid quantification of pyrrolizidine alkaloids from plant extracts by UHPLC-QTOF-MS","authors":"Benedikt Schwarz ,&nbsp;Shah Hussain ,&nbsp;Christian W. Huck ,&nbsp;Thomas Jakschitz ,&nbsp;Moritz Rubner ,&nbsp;Günther K. Bonn","doi":"10.1016/j.jpba.2025.116675","DOIUrl":"10.1016/j.jpba.2025.116675","url":null,"abstract":"<div><div>The aim of this work was to develop and validate a rapid dispersive-solid-phase extraction method for the quantification of pyrrolizidine alkaloids (PA) from plant extracts. The method was focused on the significant removal of the intricate matrix to ensure good sensitivity for the subsequent instrumental analysis of PA. This was achieved by employing nano-zirconium silicate (NZS) as a dispersive-SPE sorbent. The specific affinity of NZS for PAs allowed for the effective removal of a substantial portion of the complex matrix, thereby significantly improving the sensitivity of the method, compared to the common methods, were no specific enrichment of the PAs on the SPE sorbent is achieved. Ultra-high-performance liquid chromatography coupled to high resolution time-of-flight mass spectrometry (UHPLC/TOF MS) was used for the qualitative and quantitative analysis of PA. The procedure demonstrated high recoveries for the standard compounds spiked into a blank verbena extract at different concentrations. Recovery rates of 72–95 % for PA, and 30–70 % for their respective N-oxides (PANO) could be obtained. The method was compared to the most commonly used C18 SPE sorbent, and demonstrated a significant lower limit of quantification (LOQ) of 0.64–4.5 ng mL⁻¹ as compared to 4.98–25.7 ng mL⁻¹. The method was validated in accordance with ICH guidelines. PA standards had a linear response between 5 and 150 ng mL ⁻¹ and demonstrated a co-efficient of variance below ± 3 % with a % relative error below ± 15. The presented analytical approach was also tested for the determination of PA from contaminated <em>Verbenae herba</em> extract with success. The presented scheme improves the clean-up efficacy of the already used stationary phases for PA analysis and provides a great alternative analytical tool for the isolation of PAs from plant extracts.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116675"},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification and clinical performance of serum parathyroid hormone 1–84 via immunocapture coupled to LC–MS/MS in chronic renal failure","authors":"Haiwei Cao ,&nbsp;Yuting Jin ,&nbsp;Yingwu Wang ,&nbsp;Hao Wang ,&nbsp;Yijia Qin ,&nbsp;Xinhua Guo ,&nbsp;Suyan Tian ,&nbsp;Jing Huang ,&nbsp;Yanyan Li","doi":"10.1016/j.jpba.2025.116678","DOIUrl":"10.1016/j.jpba.2025.116678","url":null,"abstract":"<div><div>Accurate measurement of serum parathyroid hormone (PTH) is crucial for diagnosing and managing endocrine and osteological diseases. Conventional immunoassay methods struggle with cross reactivity issues between full-length PTH and truncated fragments or post-translationally modified forms. Both the standardization of PTH assays and the peptide's stability are concerning. This study addresses these issues by establishing an immunocapture coupled with liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to precisely quantify PTH1–84. PTH1–84 was isolated from one mL serum samples by immunocapture on a polystyrene bead and eluted from matrix, then quantitated by LC–MS/MS. The results from 268 serum samples were compared to an intact PTH immunoassay. The assay's linear range was 5.0–1000.0 pg/mL. The intra-assay coefficients of variation (CVs) ranged from 3.2 % to 6.8 %, and the inter-assay CVs ranged from 4.6 % to 9.5 %. The extraction efficiencies were 98.0 %–100.5 %, with no significant matrix effects observed after internal standard correction. The correlation coefficient between LC–MS/MS and immunoassay was 0.989, but the bias between the methods was substantial. Nevertheless, the immunocapture purification coupled LC–MS/MS method offers a promising approach for accurate PTH measurement.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116678"},"PeriodicalIF":3.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023505","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 determination of etomidate and its structural analogues in e-liquid by probe electrospray ionization quadrupole time-of-flight mass spectrometry","authors":"Meiting Lin ,&nbsp;Zhen Zhang ,&nbsp;Qun He ,&nbsp;Hongyuan Hao ,&nbsp;Ping Xiang ,&nbsp;Junbo Zhao","doi":"10.1016/j.jpba.2025.116677","DOIUrl":"10.1016/j.jpba.2025.116677","url":null,"abstract":"<div><div>Etomidate and its structural analogues, which have anesthetic effects, are classified as controlled psychotropic drugs. Electronic cigarettes (e-cigarettes) have become more and more popular. With the increase of adding etomidate and its analogues to electronic liquids (e-liquids), there is a trend of abuse, which is a tough problem urgently need to be solved. This seriously affects the health and security of the public and the development of society. A simple, rapid and effective screening method is very crucial for their identification. In this study, we applied a newly developed method, probe electrospray ionization quadrupole time-of-flight mass spectrometry (PESI-QTOF-MS) with DPiMS QT ion source to analyze etomidate and its analogues in e-liquids. It allowed identification in 0.3 min with lower sample usage. Isomers can be distinguished by ion abundance ratios at collision energy (CE) 15 eV, which provided possibility for distinguishing more isomers by in-situ mass spectrometry. Limit of detection (LOD) and limit of quantitation (LOQ) of four substances were 20 ng/mL and 50 ng/mL, respectively. Good linear relationships were obtained in the concentration range of 50–5000 ng/mL with little matrix effect. The accuracy, precision, dilution effect and carryover of the method were also validated. Positive specimens (n = 38) were analyzed by both PESI-QTOF-MS and gas chromatography-mass spectrometry (GC-MS). There were five impurities including nicotine, cooling agent and flavorings were investigated by PESI-QTOF-MS, which provided the possibility for tracing the origin of illegal e-liquids. This study will help solve the backlog of cases and improve work efficiency effectively by reducing analysis time. Furthermore, it meets the need of addressing current situation of drug control and can assist forensic laboratories in investigating cases. It also demonstrates the application prospects of rapid screening in new drugs.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116677"},"PeriodicalIF":3.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006831","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":"Chromatographic analysis and pKa evaluation of active pharmaceutical ingredients in anti-metastatic breast cancer: Green vs. conventional RPLC","authors":"Fatmanur Kalkir ,&nbsp;Ebru Çubuk Demi̇ralay ,&nbsp;Yaşar Doğan Daldal ,&nbsp;Hülya Yilmaz","doi":"10.1016/j.jpba.2025.116671","DOIUrl":"10.1016/j.jpba.2025.116671","url":null,"abstract":"<div><div>This study aimed to determine the chromatographic retention and dissociation/protonation constant (pK_a) values of lapatinib and tamoxifen, key drugs used in metastatic breast cancer treatment, at 37°C using both conventional and green high-performance liquid chromatography (HPLC) methods. Qualitative analysis was conducted on an XTerra C18 column (250 ×4.6 mm I.D., 5 μm particle size) at a flow rate of 1 mL/min. Hydroorganic mixtures with 45 %, 50 %, 55 %, and 60 % (v/v) organic modifiers were used to evaluate the retention times of the compounds. The compatibility of pK_a values <span><math><mrow><mfenced><mrow><mmultiscripts><mrow><mi>pK</mi></mrow><mrow><mi>a</mi></mrow><none></none><mprescripts></mprescripts><mrow><mi>s</mi></mrow><mrow><mi>s</mi></mrow></mmultiscripts></mrow></mfenced></mrow></math></span> of the compounds in water-organic solvent mixtures obtained from these studies, which were carried out without any significant change in liquid chromatography performance, with the values obtained by the conventional method is remarkable. The <span><math><mmultiscripts><mrow><mi>pK</mi></mrow><mrow><mi>a</mi></mrow><none></none><mprescripts></mprescripts><mrow><mi>s</mi></mrow><mrow><mi>s</mi></mrow></mmultiscripts></math></span> values determined in this study were correlated with the macroscopic parameters of acetonitrile, methanol, ethanol and the pK_a (<span><math><mrow><mmultiscripts><mrow><mi>pK</mi></mrow><mrow><mi>a</mi></mrow><none></none><mprescripts></mprescripts><mrow><mi>w</mi></mrow><mrow><mi>w</mi></mrow></mmultiscripts><mrow><mo>)</mo><mspace></mspace></mrow></mrow></math></span>values of lapatinib and tamoxifen in water were calculated. The <span><math><mmultiscripts><mrow><mi>pK</mi></mrow><mrow><mi>a</mi></mrow><none></none><mprescripts></mprescripts><mrow><mi>w</mi></mrow><mrow><mi>w</mi></mrow></mmultiscripts></math></span> values calculated from these studies are compatible with each other and with the literature values. The environmental impact of the study, which was carried out using the green method and the conventional RPLC method, was evaluated using the Green Solvent Selection Tool (GSST), Green Analytical Procedures Index (GAPI), and Analytical Greenness Metric Approach (AGREE).</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116671"},"PeriodicalIF":3.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007221","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":"Hydrophilic interaction liquid chromatography-tandem mass spectrometry analysis of oligosaccharides and iridoid glycosides in rat plasma: Pharmacokinetic characterization of previously overlooked oligosaccharides from Radix Rehmanniae","authors":"Hanyang Wang ,&nbsp;Yue Du ,&nbsp;Chunwei Zhou ,&nbsp;Yan Wang ,&nbsp;Xin Wang","doi":"10.1016/j.jpba.2025.116670","DOIUrl":"10.1016/j.jpba.2025.116670","url":null,"abstract":"<div><div>Radix Rehmanniae (RR) is a widely used herb in traditional Chinese Medicine with properties of tonifying the kidneys and nourishing the blood. Both raw and processed RR are effective for the treatment of diabetes in clinical practice. Oligosaccharides and iridoid glycosides are the primary active components responsible for the anti-diabetic effects of RR. In this study, a rapid and sensitive hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC−MS/MS) method was developed for simultaneous determination of oligosaccharides (raffinose, manninotriose and stachyose) and iridoid glycosides (catalpol and ajugol) in rat plasma. Significant analytical challenges were encountered during method development, including distinct retention behaviors of oligosaccharides and iridoid glycosides, low ionization and extraction efficiency of oligosaccharides, thermal instability of catalpol and reduced column performance. The strategies to overcome these challenges were presented by optimizing chromatographic separation, mass spectrometric detection and sample preparation. The best separation was achieved using an Accucore-150-Amide-HILIC column (100 mm × 2.1 mm, 2.6 μm) at 50 °C with mobile phase consisted of acetonitrile and ammonium acetate (2.5 mM) under gradient elution. Ammonium adduct ions produced by positive electrospray ionization were chosen as precursor ions for multiple reaction monitoring transitions. The established HILIC−MS/MS method exhibited good linearity (<em>r</em> &gt; 0.9937) with the lower limits of quantification of 0.01–0.2 μg/mL using only 50 µL of plasma sample. The method was successfully applied to pharmacokinetic characterization of oligosaccharides and iridoid glycosides in normal and type 2 diabetic rats following intragastric administration of raw and processed RR extracts.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116670"},"PeriodicalIF":3.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006647","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":"Cellulose filter paper immobilized acetylcholinesterase for rapid screening of enzyme inhibitors in Phyllanthus emblica L.","authors":"Yangzom Dawa ,&nbsp;Yong-Chen Hua ,&nbsp;Fang-Di Hu ,&nbsp;Juan Chen","doi":"10.1016/j.jpba.2025.116669","DOIUrl":"10.1016/j.jpba.2025.116669","url":null,"abstract":"<div><div>Acetylcholinesterase (AChE) is widely recognized as a promising therapeutic target enzyme for Alzheimer's disease (AD). The screening of AChE inhibitors (AChEIs) holds great significance for the treatment of AD. In this study, cellulose filter paper (CFP) -immobilized AChE was prepared and firstly applied to screening AChEIs from 30 % ethanol extract of <em>Phyllanthus emblica L.</em> fruits combined with ultra-high performance liquid chromatography quadrupole time-of-fight mass spectrometry (UHPLC-Q-TOF-MS/MS). Using CFP-immobilized AChE as the bait, AChEIs were harvested and the instantaneous separation characteristics of CFP were utilized to further facilitate the separation of the complex from the inactive components. Ultimately, 27 compounds specifically bound with AChE were screened and identified using UHPLC-Q-TOF-MS/MS. Additionally, molecular docking was employed to explore the binding mechanisms between screened potential inhibitors and AChE. The results show that, most of the screened compounds were found to exhibit higher affinity that of the positive control (huperzine A), and all the compounds expect mucic acid to be well embedded into the active pocket of AChE. To verify the reliability of the screening method and molecular docking, two commercial standards geraniin and ellagic acid were experimented with an AChE inhibition assay in <em>vitro</em>. The results showed that both compounds were found to effectively inhibit AChE with IC₅₀ values of 42.42 ± 7.10 μM, 172.43 ± 9.22 μM. The developed method exhibits the advantages of rapidness and effectiveness in screening of AChEIs from complex herbal extracts.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"256 ","pages":"Article 116669"},"PeriodicalIF":3.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007233","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}