Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Bringing an immuno-PCR-based pharmacodynamic biomarker assay for reduced human IL-33 in serum, plasma, and aqueous humor into the clinic","authors":"John Hok Nin Lowe ,&nbsp;Trung Nguy ,&nbsp;Randall Dere ,&nbsp;Vahan B. Indjeian ,&nbsp;Mauricio Maia","doi":"10.1016/j.jpba.2025.117095","DOIUrl":"10.1016/j.jpba.2025.117095","url":null,"abstract":"<div><div>Immuno-polymerase chain reaction (iPCR) is an analytical technology that combines the specificity of antibody reagents with the sensitivity of polymerase chain reaction (PCR) signal amplification. Here we describe the optimization and qualification of an ultra-sensitive iPCR method designed to detect and quantify active (reduced form) interleukin-33 (IL-33) in human samples. The modified assay incorporates several improvements over a previous version utilized in research studies. The changes aimed at making the assay more suitable to the rigorous requirements promulgated to biomarker assays supporting clinical development of new human therapeutics. The assay can accurately measure sub-picogram/mL levels of reduced IL-33, and has a dynamic range of 977–1000,000 fg/mL. We found this iPCR-based format to be versatile, and we believe it can be adapted to detect and quantify other low-level cytokines in human matrices when limited sample volumes are available.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117095"},"PeriodicalIF":3.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851958","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":"Species discrimination and VIP-stacking quantitative models for Curcumae Rhizoma utilizing multi-modal spectra combined with machine learning algorithm","authors":"Xueyang Ren,&nbsp;Youyi Sun,&nbsp;Ting He,&nbsp;Jiamu Ma,&nbsp;Jianling Yao,&nbsp;Mingxia Li,&nbsp;Mengyu Sun,&nbsp;Wei Liu,&nbsp;Feng Zhang,&nbsp;Yu Cao,&nbsp;Yongqi Yang,&nbsp;Letian Ying,&nbsp;Yuqing Yang,&nbsp;Ruijuan Yuan,&nbsp;Gaimei She","doi":"10.1016/j.jpba.2025.117092","DOIUrl":"10.1016/j.jpba.2025.117092","url":null,"abstract":"<div><div><em>Curcumae Rhizoma</em> (<em>Ezhu</em>) is a multi-species herbal medicine with excellent medicinal value and development potential. However, challenges such as the difficulty in differentiating its varieties and the limitations of current methods for determining minor component content, which are time-consuming and cumbersome, necessitate improved approaches. Spectroscopic techniques combined with chemometrics offer a powerful alternative for developing qualitative and quantitative models, and the spectral data fusion has emerged as a key research hotpot. This study employed multi-modal spectroscopy including Fourier transform infrared (FT-IR), Fourier transform near-infrared (FT-NIR), and ultraviolet (UV) combined with multivariate algorithms to establish species discrimination and content prediction models for minor constituents in <em>Ezhu</em>. For qualitative analysis, linear discriminant analysis (LDA), k-nearest neighbor (KNN), and decision tree (DT) models based on fused UV+FT-NIR+FT-IR spectral data achieved 100 % classification accuracy. For quantitative analysis, a novel variable importance in projection (VIP)-guided stacking ensemble strategy was proposed, leveraging VIP scores derived from partial least squares regression (PLSR) to optimize base-learner combinations. This approach successfully constructed robust models for predicting the content of (3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane), (1,7-bis-(4-hydroxychalcone)-3,5-dihydroxy-heptane), (3<em>S</em>,5<em>S</em>)-3-acetoxy-5-hydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane, germacrone, zederone, curzerene, and curdione. Compared to conventional machine learning models and prior studies, the VIP-stacking ensemble models demonstrated superior predictive accuracy and robustness. This work highlights the efficacy of spectral data fusion in both qualitative and quantitative analyses and validates the potential of VIP-stacking ensemble strategies to enhance the performance of content prediction models. This study not only offers a more effective way to identify and quality control of <em>Ezhu</em>, but also provides a promising approach for species authentication and quality control in pharmaceutical, agricultural, and food science applications.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117092"},"PeriodicalIF":3.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841651","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":"Comparative proteomics and metabolomics unveil regional variations in Dendrobium officinale","authors":"Shenghong Guan ,&nbsp;Guoqing Jin ,&nbsp;Xiaoyong Zhang ,&nbsp;Amin Liu ,&nbsp;Yumei Yan ,&nbsp;Shuo Chai ,&nbsp;Shuxin Chen ,&nbsp;Dan Tang ,&nbsp;Shouxin Li ,&nbsp;Jingkui Tian ,&nbsp;Zhajun Zhan ,&nbsp;Hua Gu ,&nbsp;Qinglin Li","doi":"10.1016/j.jpba.2025.117087","DOIUrl":"10.1016/j.jpba.2025.117087","url":null,"abstract":"<div><div><em>Dendrobium officinale</em> (<em>D. officinale</em>) is a well-known medicinal plant in China with a variety of pharmacological uses. Although <em>D. officinale</em> from different regions has diverse active components, it remains unclear what are the underlying causes of these variations. Inter-regional variations in <em>D. officinale</em> from Anhui (AH), Zhejiang (ZJ), and Yunnan (YN) were preliminarily characterized through physiological and biochemical indicator assessments, followed by comprehensive proteomic and metabolomic profiling to identify differential protein signatures and metabolic patterns. The findings demonstrated that although <em>D. officinale</em> samples from different geographical origins shared a similar metabolic profile, the concentrations of key bioactive compounds (e.g., polysaccharides and dendrobine) varied significantly. AH, ZJ and YN were found to have 205 differently expressed metabolites and 1689 differentially expressed proteins. It was shown that the phenylpropanoid biosynthesis and flavonoid biosynthesis pathways were the primary targets of the differentially expressed proteins and metabolites. Phenylalanine ammonia-lyase, 4-coumarate-CoA ligase, caffeoyl shikimate esterase, chalcone isomerase, and chalcone synthase are the main enzymes involved in these metabolic pathways. This work offers a fresh perspective on the diversity of <em>D. officinale</em> origin in terms of proteins and metabolites, which is useful for thoroughly examining the growth pattern, therapeutic potential, and possible bioactive elements of <em>D. officinale</em>.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117087"},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809450","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":"Comparative analysis of 30 East Asian traditional medicine formulations revealed the applicability of 1H NMR spectroscopy in quality control","authors":"Eunah Jeong,&nbsp;Huong T. Pham,&nbsp;Kyo Bin Kang","doi":"10.1016/j.jpba.2025.117089","DOIUrl":"10.1016/j.jpba.2025.117089","url":null,"abstract":"<div><div>Multi-herbal formulations in East Asian traditional medicine have long played an important role in disease treatment and modern drug discovery. Despite extensive efforts toward standardization, quality control remains challenging due to their chemical complexity and richness in polar metabolites, which complicate chromatography-based methods. Nuclear Magnetic Resonance (NMR) spectroscopy offers an alternative solution; however, previous studies have mainly focused on single formulations, with limited systematic analysis across multiple formulations. This study explores the applicability of ¹H NMR spectroscopy for quality control in East Asian traditional medicine products by analyzing 86 batch samples from 30 formulations, manufactured in a GMP-certified facility. Pearson correlation efficients between binned spectra were calculated to evaluate both batch-to-batch and formulation-to-formulation similarities. Batch-to-batch correlations were consistently high (r &gt; 0.99), indicating excellent reproducibility. In contrast, formulation-to-formulation correlations ranged from 0.72 to 1.00, largely influenced by saccharide abundance. Additionally, three major specialized metabolites—paeoniflorin, naringin, and baicalin—were identified based on their characteristic proton signals, and their presence correlated with the herbal composition of each formulation. These findings highlight the potential of ¹H NMR analysis as an effective solution for the quality control of traditional medicines, addressing the challenges posed by their chemical complexity while ensuring consistency and providing detailed insights into metabolite variations among formulations.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117089"},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779399","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":"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}