Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Development and optimization of a high-throughput LC-MS/MS method for the simultaneous determination of Exatecan and its Cathepsin B-sensitive prodrug, and ARV-825 in rat plasma: Application to pharmacokinetic study","authors":"Xiaolan Xu,&nbsp;Yangyang Liu,&nbsp;Qing Yan,&nbsp;Chenxia Bai,&nbsp;Xiaohua Ran,&nbsp;Jing Li,&nbsp;Jiaming Zhang,&nbsp;Qikun Jiang,&nbsp;Tianhong Zhang","doi":"10.1016/j.jpba.2025.116746","DOIUrl":"10.1016/j.jpba.2025.116746","url":null,"abstract":"<div><div>For most cancers, the combination of chemotherapy drugs is a promising approach. The combination of DNA damage agent Exatecan and proteolysis targeting chimera (PROTAC) agent ARV-825, which is a selective bromodomain-containing protein 4 degrader, can further improve efficacy through the DNA damage-repair mechanism. The Cathepsin B-sensitive prodrug with high albumin affinity of Exatecan (C14-VC-PAB-Exa) was introduced and co-encapsulated with ARV-825 into the nano-drug delivery system for improving the physicochemical properties of the two drugs. To promote the translation of Exatecan and the PROTAC into the clinics, it is important to develop a reliable and high-throughput bioanalytical method for the simultaneous determination of Exatecan, C14-VC-PAB-Exa, and ARV-825 that can evaluate the pharmacokinetic behaviors of the analytes. In this study, an HPLC-MS/MS method after preparation by one-step protein precipitation was developed and fully validated. The analytes were eluted completely on a ZORBAX SB-C18 column by gradient elution. Multiple reaction monitoring mode with positive electrospray ionization was applied to quantify the analytes. The validated method on selectivity, linearity (<em>r</em> ≥ 0.995), precision and accuracy (&lt; 15 %), extraction recovery (&gt; 88.0 %), matrix effect (&lt; 9.1 %), carry-over, and stability were within the predefined acceptance criteria. The method was successfully applied to the pharmacokinetic study of Exatecan, C14-VC-PAB-Exa, and ARV-825 in rats for the first time. The proposed robust and economical method will be an alternative bioanalytical procedure for Exatecan and ARV-825 in the future. What is more, the present work could provide a reference for the clinical combination of the two drugs.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116746"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420116","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":"Separation, characterization and cytotoxicity of unknown forced degradation impurity of selpercatinib using Prep-LC, HRMS and NMR","authors":"Qin Wang ,&nbsp;Wenyi Wu ,&nbsp;Rongwei Sun ,&nbsp;Liangliang Cai","doi":"10.1016/j.jpba.2025.116747","DOIUrl":"10.1016/j.jpba.2025.116747","url":null,"abstract":"<div><div>Selpercatinib (LOXO-292) is a newly marketed oral selective receptor tyrosine kinase inhibitor targeting rearranged during transfection (RET), demonstrating precise therapeutic effects against RET-positive non-small cell lung cancer and thyroid cancer. In this study, an unknown acid forced degradation impurity of selpercatinib, designated sel-1, was isolated and purified using semi-preparative liquid chromatography (semi-Prep-LC). The purified sel-1 showed a chromatographic purity of 99.1 % as determined by high-performance liquid chromatography (HPLC). It appeared as a white amorphous powder, with a maximum absorption peak at 235 nm and a chemical formula of C₂₈H₂₉N₇O₃. Its molecular structure was elucidated using high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR). sel-1 was identified as 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-oxo-1,6-dihydropyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-<em>a</em>]pyridine-3-carbonitrile. In vitro MTT assays revealed that sel-1 exhibited significant antitumor activity, particularly against HepaRG and MKN-1 cell lines, with stronger inhibition than selpercatinib. The study contributes to enhancing the quality control standards for selpercatinib and suggests that sel-1 holds potential for further drug development.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116747"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420117","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 networking: An efficient tool for discovering and identifying natural products","authors":"Yongjian Wang ,&nbsp;Yadan Wang ,&nbsp;Zhongmou Zhang ,&nbsp;Kailing Xu ,&nbsp;Qiufang Fang ,&nbsp;Xianfu Wu ,&nbsp;Shuangcheng Ma","doi":"10.1016/j.jpba.2025.116741","DOIUrl":"10.1016/j.jpba.2025.116741","url":null,"abstract":"<div><div>Natural products (NPs), play a crucial role in drug development. However, the discovery of NPs is accidental, and conventional identification methods lack accuracy. To overcome these challenges, an increasing number of researchers are directing their attention to Molecular networking (MN). MN based on secondary mass spectrometry has become an important tool for the separation, purification and structural identification of NPs. However, most new tools are not well known. This review started with the most basic MN tool and explains it from the principle, workflow, and application. Then introduce the principles and workflows of the remaining eight new types of MN tools. The reliability of various MNs is mainly verified based on the application of phytochemistry and metabolomics. Subsequently, the principles and applications of 12 structural annotation tools are introduced. For the first time, the scope of 9 kinds of MN tools is compared horizontally, and 12 kinds of structured annotation tools are classified from the type of compound structure suitable for identification. The advantages and disadvantages of various tools are summarized, and make suggestions for future application directions and the development of computing tools in this review. MN tools are expected to enhance the efficiency of the discovery and identification in NPs.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"259 ","pages":"Article 116741"},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509852","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 and characterization of related substances in DTX-AI via LC–QTOF–HRMS","authors":"Peng-wei Hu ,&nbsp;Wen-yu Zou ,&nbsp;Zhao-guang Li ,&nbsp;Hai-dao Li ,&nbsp;Jun Liu ,&nbsp;Min Song ,&nbsp;Yu-ting Lu ,&nbsp;Tai-jun Hang","doi":"10.1016/j.jpba.2025.116739","DOIUrl":"10.1016/j.jpba.2025.116739","url":null,"abstract":"<div><div>10-<em>O</em>-4-Ketonephenyl carbamate docetaxel (DTX-AI) is a synthetic taxane compound that exerts antitumor effects by inhibiting microtubule depolymerization and promoting microtubule dimer synthesis. Owing to the poor water solubility of DTX-AI, the liposomal formulation for injection was developed and prepared. <em>In vitro</em> experiments showed that DTX-AI and its liposomal formulation outperformed DTX in terms of antitumor efficacy at much lower concentrations, with correspondingly lower toxicity. The quality and stability as well as liposomal formulation of DTX-AI directly impact its therapeutic efficacy and safety. This study utilized LC–QTOF–HRMS to isolate and identify the process and stress testing degradation related substances (RSs) in DTX-AI. A total of 23 RSs were detected and identified in the Active pharmaceutical ingredient (API) via positive ESI–HRMS, and their structures and degradation pathways were elucidated and summarized. These findings provide valuable insights into the optimal production processes, formulations, storage conditions, and quality control for DTX-AI.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116739"},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420115","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":"Development and robust optimization of the RP-HPLC method for the determination of riociguat and its four impurities in tablets using the AQbD approach","authors":"Milena Rmandić ,&nbsp;Marija Rašević ,&nbsp;Jelena Stanković ,&nbsp;Mira Zečević ,&nbsp;Biljana Otašević ,&nbsp;Ana Protić ,&nbsp;Anđelija Malenović","doi":"10.1016/j.jpba.2025.116742","DOIUrl":"10.1016/j.jpba.2025.116742","url":null,"abstract":"<div><div>The aim of this work was to develop and optimize the RP-HPLC method for the qualitative and quantitative analysis of riociguat and its four impurities using the Analytical Quality by Design concept. Risk assessment was carried out as a combination of Ishikawa diagram - Control, Noise and eXperimental - Failure mode and effect analysis from where critical method parameters for this study were selected (i.e. acetonitrile content in the mobile phase, concentration of ammonium acetate in aqueous part of mobile phase and column temperature). Their effects on critical method attributes (retention factor of the last eluting peak and separation of critical peak pairs) were further analyzed using the Design of Experiments methodology. The Design Space was defined as the area in which the robustness of the qualitative performance of the developed method is confirmed. Monte Carlo simulations were applied to achieve the defined quality by propagating the error resulting from the calculated coefficients of the mathematical models. The optimal chromatographic conditions included separation on an Xterra® RP18 (150 × 4.6 mm, 3.5 µm) column with a mobile phase consisting of 34 % of acetonitrile and 66 % of aqueous 15 mM ammonium acetate solution pH 5.5, at a column temperature of 36°C. The flow rate was 1 mL/min, the detection wavelength was 210 nm, while the injection volume was 20 µL. Validation of the developed method was performed, which confirmed its reliability in determining the content of riociguat and its four impurities in tablets.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116742"},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402722","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":"Development and application of UHPLC-MS/MS method to quantify eculizumab in PNH patients","authors":"Zhihui Zhang ,&nbsp;Ning Sheng ,&nbsp;Xin Liu ,&nbsp;Bing Han ,&nbsp;Bo Zhang ,&nbsp;Jinlan Zhang","doi":"10.1016/j.jpba.2025.116740","DOIUrl":"10.1016/j.jpba.2025.116740","url":null,"abstract":"<div><div>To evaluate the optimal treatment scheme and minimize unnecessary use of the highly expensive orphan drug eculizumab, therapeutic drug monitoring should be performed. The aim of this study is to establish a validated ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify the concentration of eculizumab in human plasma. Plasma samples were prepared using protein G beads, followed by trypsin digestion. A signature peptide for eculizumab (LLIYGATNLADGVPSR) was selected and quantified by UHPLC-MS/MS in the multiple reaction-monitoring mode. The stable isotope-labeled signature peptide *LLIYGATNLADGVPSR (¹³C₆, ¹⁵N₄-labeled arginine) was used as the internal standard (IS). The UHPLC-MS/MS exhibited good specificity and no matrix effects when employing IS. The calibration curves of eculizumab presented a strong linear relationship from 5 to 1000 µg·mL⁻¹, surpassing the scope of previously published methods and encompassing the concentration levels typically observed in clinical samples. A total of 15 Chinese PNH patients treated with eculizumab were enrolled. The successful application of the method to clinical samples and the data agreement with the ELISA data both demonstrated that established UHPLC-MS/MS is a reliable approach for quantifying eculizumab. Furthermore, this is the first published method used to determine the eculizumab concentration in Chinese PNH patients. The study also suggests that there are large interindividual variations in eculizumab pharmacokinetics among Chinese PNH patients.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116740"},"PeriodicalIF":3.1,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386982","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 potential drug targets for four site-specific cancers by integrating human plasma proteome with genome","authors":"Zhangjun Yun ,&nbsp;Zhu Liu ,&nbsp;Ziyi Sun ,&nbsp;Xiang Yan ,&nbsp;Qianru Yang ,&nbsp;Shaodan Tian ,&nbsp;Xiao Li ,&nbsp;Li Hou","doi":"10.1016/j.jpba.2025.116731","DOIUrl":"10.1016/j.jpba.2025.116731","url":null,"abstract":"<div><div>Drug targets supported by genetic evidence with a several-fold higher probability of success in clinical trials. We performed a comprehensive proteome-wide Mendelian randomization (MR) analysis to identify causal proteins and potential therapeutic targets for four site-specific cancers. A total of 13,248 protein quantitative trait loci for 4853 plasma proteins were utilized for proteome-wide MR analysis. Identification of cancer causal proteins in the discovery cohort and further validation in the replication cohort. Colocalization, summary-data-based MR (SMR) analysis, and transcriptome‑wide association studies (TWAS) were performed to check the accuracy of the candidate proteins. Two-step MR analysis was used to explore the effects of plasma protein-mediated 248 modifiable factors on cancer. Phenome-wide MR (Phe-MR) analysis, druggability evaluation, and single-cell type expression analysis further assessed the potential of causal proteins. Combining the results of the meta-analysis of MR estimates from the two cohorts, 21, 2, 24 and 1 causal proteins were identified in breast, lung, prostate and stomach cancers, respectively. Evidence from colocalization, SMR analysis, and TWAS highlighted CD36, DNPH1, and PLXND1 as the most promising drug targets for breast cancer, and ZNF175 for prostate cancer. 1 new potential biomarker (PLXND1) for breast cancer, 2 new promising targets (RELL1, DEFB119) for lung cancer, and 8 new circulating biomarkers (ARFIP2, CCN6, CTRB2, HTR7, MRPL33, TNFRSF6B, VAMP5, ZNF175) for prostate cancer were firstly reported. Some plasma proteins may mediate the association of these cancers with other systemic diseases. Additionally, genetically predicted higher BMI and overweight may reduce breast cancer risk by altering CASP8, ADM, PLXND1, TNFRSF9, ULK3 and VSIG4 protein levels. Causal proteins of breast and prostate cancer were expressed predominantly on macrophages in cancerous tissues. This study genetically identified several cancer causal proteins which provided new perspectives for the understanding of the etiology and development of novel targeted drugs for cancer.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116731"},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379108","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":"Widely targeted plasma lipidomic analysis of Term Low Birth Weight Infants: unraveling signatures and implications for early growth patterns","authors":"Jing Liu ,&nbsp;Qi Sun ,&nbsp;Lijuan Tang ,&nbsp;Di Lv ,&nbsp;Yuanmei Chen ,&nbsp;Fang Ye ,&nbsp;Die Liu ,&nbsp;Haixiao Liang ,&nbsp;Chao Wang ,&nbsp;Qi Zhang","doi":"10.1016/j.jpba.2025.116732","DOIUrl":"10.1016/j.jpba.2025.116732","url":null,"abstract":"<div><div>Low birth weight is recognized as a risk factor for adult metabolic and cardiovascular diseases. This study investigates whether term low birth weight (TLBW) neonates, who have been exposed to unfavorable settings, demonstrate compromised lipid metabolism. A widely targeted lipidomic analysis was conducted using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) on 59 plasma samples (28 TLBW and 31 term normal birth weight (TNBW) neonates. We conducted univariate and multivariate analyses to identify differential lipids. Spearman's correlation coefficient assessed the association between lipid content at birth and Z-scores for the subsequent physical growth of enrolled children. A total of 1523 lipids in 36 subcategories across 6 major categories were detected. 269 differential lipids were discerned, with 114 up-regulated and 155 down-regulated. In the TLBW group, we observed higher levels of sphingomyelins (including SM(d18:1/16:1), SM(d18:2/23:1), SM(d18:1/22:0), and SM(d18:2/24:1)), Hex3Cer(d18:1/16:0), as well as phosphatidylcholines (PC(O-14:0_20:4) and PC(O-16:0_20:4)), and cholesterol esters (CE (20:4)). In contrast, phosphatidylethanolamines (PE) such as PE (18:2_22:1), PE (18:1_22:1), and triglyceride (TG(10:0_16:2_18:2)) were lower. The KEGG enrichment analysis revealed a consistent alteration in both sphingolipid metabolism and steroid biosynthesis. Moreover, PC(O-16:0_20:4), Hex3Cer(d18:1/16:0), and CE(20:4) exhibited positive correlations with the Z-score of height-for-age at follow-up, while PE(O-18:1_24:4) and PS(20:2_22:4) showed negative correlations with the Z-score of weight-for-age. Our findings reveal novel lipidomic differences between TLBW and TNBW neonates. The observed lipid variations at birth, including sphingomyelins and glycerophospholipids, could affect subsequent growth. Further studies are needed to validate these findings in diverse populations, address confounding factors, and investigate underlying mechanisms.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116732"},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376964","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":"Guilty by dissociation: Part C: Enantiomeric separation of diphenidine-derived new psychoactive substances (NPS) by polar organic chiral high performance liquid chromatography (HPLC) on polysaccharide-based stationary phases","authors":"Melvin R. Euerby ,&nbsp;Benjamin S. Barrett ,&nbsp;Andrew Costello ,&nbsp;Tivadar Farkas ,&nbsp;Michael.A. Sallenger ,&nbsp;Oliver B. Sutcliffe","doi":"10.1016/j.jpba.2025.116728","DOIUrl":"10.1016/j.jpba.2025.116728","url":null,"abstract":"<div><div>This study describes a simple and practical HPLC analysis for the direct enantiomeric separation of a range of 32 novel diphenidine derived psychoactive substances using a range of six polysaccharide-based chiral stationary phases employing a single generic polar organic solvent chromatographic mobile phase. Temperature was employed to optimize the chemo and enantiomeric selectivity. Baseline separation and differentiation of both the enantiomers and positional isomers (i.e., regioisomers) of the 2-, 3- and 4-methoxphenidines was achieved with the chiral selector cellulose <em>tris</em>(3-chloro-4-methylphenylcarbamate) coated onto silica. The latter proved to be the best of the six chiral stationary phases investigated in that it generated enantiomeric separation of 25 of the 26 monosubstituted diphenidines with resolution values &gt; 1.5. It yielded the optimum separation for 21 of the 26 diphenidines (resolution values ranged from 2.9 – 22.4) including the 2-, 3- and 4-positional isomers of eight diphenidine derivatives. Excellent separation of all 26 monosubstituted diphenidines (i.e., resolution values &gt; 1.5) and peak shape (i.e., typical tailing factors between 0.9 – 1.2) could be achieved by using Lux Cellulose-2 and Lux <em>i</em>-Amylose-3 columns. The nature of the polysaccharide-based chiral selector was demonstrated to be extremely important in determining the degree of chiral resolution. The location of the monosubstituent on the 1-phenyl ring of the diphenidine was shown to be important in promoting chiral resolution. Greater chiral discrimination was typically observed for substituents in the 4-position compared to those in the 2-position of the 1-phenyl ring. The chiral HPLC methodology displayed good chemo and enantiomeric selectivity of the mono-, di- and trisubstituted diphenidine regioisomers. Enantiomer elution order reversal was highlighted with 2-methoxphenidine enantiomers as a function of the chiral stationary phase. The (R)-enantiomer eluted before the (S)-enantiomer on cellulose-based chiral stationary phase whereas the reverse occurred with the amylose-based phases. Application of the methodology to the analysis of real-life samples of 2-methoxphenidine and diphenidine confirmed that these psychoactive substances were being traded as racemic products. Commonly used adulterants in powdered samples were shown not to interfere with the chiral analysis of 2-methoxphenidine and diphenidine.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116728"},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420599","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":"Exploring the mechanism of action of Bailemian capsule in the treatment of insomnia based on metabolomics, 16S rRNA with UPLC-QE-Orbitrap-MS/MS","authors":"Yuelin Bi ,&nbsp;Peng Wang ,&nbsp;Wanting Ye ,&nbsp;Shiyun Zhang,&nbsp;Yang Bai,&nbsp;Haoran Xu,&nbsp;Gengyuan Yu,&nbsp;Tonghua Zhang,&nbsp;Jiaqi Wang,&nbsp;Ying Liu,&nbsp;Yikun Sun","doi":"10.1016/j.jpba.2025.116733","DOIUrl":"10.1016/j.jpba.2025.116733","url":null,"abstract":"<div><div>Bailemian capsule (BLMC) is composed of lily bulb, thorny <em>Acanthopanax</em> root, and other traditional Chinese medicines; it is commonly used to treat insomnia in traditional Chinese medicine. However, the active ingredients and mechanisms of action that underlie this treatment ability have not been fully explored. Here, a liquid chromatography-tandem mass spectrometry method was developed to qualitatively analyse the exogenous BLMC components that directly entered the blood and several brain regions after administration of BLMC to mice. A total of 47 compounds that directly entered the blood, including isoleucine. Moreover, there were 33, 34, 36, and 27 compounds distributed in the hypothalamus, hippocampus, frontal cortex, and temporal cortex of the mice, respectively. Subsequently, this study integrated network pharmacology, metabolomics and gut microbiota analysis to explore potential mechanism of BLMC against insomnia. The network pharmacology results suggest that BLMC affects insomnia by modulating the glutamatergic synaptic pathway. And serum and hypothalamic metabolomics analysis indicates that BLMC mainly regulates the metabolic pathways of D-Glutamine and D-Glutamic acid metabolism, significantly upregulating the differential metabolite glutamic acid and downregulating glutamine. In addition, analysis of gut microbiota indicates a close relationship between <em>norank_f_Desulfovibirosaceae</em> and glutamic acid. This study systematically revealed for the first time the potential pharmacological components of BLMC in treating insomnia, and explored its mechanism of action from multiple perspectives, laying the foundation for further exploration of the mechanism of BLMC in treating insomnia.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116733"},"PeriodicalIF":3.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372264","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}