Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Identification of blood-absorbed components of Qingkui Yuyang decoction and its mechanistic roles in ulcerative colitis based on UPLC-Q-Exactive Orbitrap-MS/MS and network pharmacology","authors":"Yunwang Chen ,&nbsp;Long Liu ,&nbsp;Yinting Wei ,&nbsp;Qing Zhang ,&nbsp;Yanping Wang","doi":"10.1016/j.jpba.2026.117408","DOIUrl":"10.1016/j.jpba.2026.117408","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurrent episodes of intestinal inflammation and mucosal injury. Qingkui Yuyang decoction (QKY), a clinically validated traditional Chinese medicinal formula, has been widely used in the treatment of UC; however, its pharmacodynamically active constituents and underlying mechanisms of action have not been fully elucidated. In this study, we explored the therapeutic mechanisms of QKY in treating UC by employing a combination of serum pharmacochemistry, network pharmacology, and molecular docking techniques. Initially, using UPLC-Q-Exactive Orbitrap-MS/MS, 28 candidate active compounds in the serum of rats treated with QKY were identified. Subsequently, network pharmacology analysis identified 43 overlapping targets between UC and the active components, and 30 related signaling pathways. Further analysis and molecular docking studies have confirmed that the key active components (Loureirin A, Berberine, Ellagic acid) possess potential for effective therapeutic effects with the core targets (RELA, AKT1). In addition, in vitro experiments demonstrated that QKY significantly downregulated the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α. QKY also markedly reduced the phosphorylation levels of NF-κB p65 and p38 MAPK, as well as the corresponding mRNA expression levels of these signaling molecules. These results suggest that QKY may exert its therapeutic effects on UC by modulating the MAPK and NF-κB signaling pathways, offering a promising strategy for the prevention and treatment of UC.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117408"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180310","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":"Sequential digestions enable identification and quantification of rapid aspartic acid isomerization in the CDR of a monoclonal antibody light chain","authors":"Jérôme Jonveaux,&nbsp;Marc Faudon,&nbsp;Pauline Heymes,&nbsp;Valentina Lucchini,&nbsp;Maria Fernanda Zuluaga Estrada,&nbsp;Michael Jahn,&nbsp;Mostafa Zarei","doi":"10.1016/j.jpba.2026.117383","DOIUrl":"10.1016/j.jpba.2026.117383","url":null,"abstract":"<div><div>Isomerization of aspartic acid (Asp) to isoaspartic acid (isoAsp) within the complementarity-determining regions (CDRs) of monoclonal antibodies (mAbs) can lead to conformational changes that decrease antigen-binding affinity. Although isomerization can significantly alter the chromatographic and electrophoretic profiles, precise localization of this modification requires a mass spectrometry-based approach, such as peptide mapping. In this work, we present a case study that investigates various analytical strategies to identify the root cause of significant changes observed in the chromatographic and electrophoretic profiles of an mAb during formulation development. LC-MS analysis of reduced mAb using high-resolution mass spectrometry, peptide mapping using trypsin digestion, and fraction collection of the newly identified peak followed by trypsin digestion suggested that isomerization occurs within the CDR of the mAb. However, due to the presence of three Asp residues within a single tryptic peptide, this modification could not be precisely localized. To overcome this limitation, we developed a sequential enzymatic digestion strategy, utilizing trypsin followed by Asp-N digestion, which enabled accurate localization and quantification of the isomerization site. The resulting data indicated that the main isoAsp signal originated from isomerization at the DS motif that increased substantially over time in the liquid formulation, while no significant change was observed in the lyophilized formulation. The level of isomerization determined through this sequential digestion method correlated well with the LC-UV quantitation data of the reduced mAb.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117383"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119332","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":"Cost-effective routine pharmaceutical testing using radial flow stream splitting HPLC columns: Quantitative analysis and performance metrics in the analysis of over-the-counter drugs","authors":"Michalina McDermott ,&nbsp;Zachary Sargeant ,&nbsp;Christopher E. Karlsen ,&nbsp;Feng Li ,&nbsp;R. Andrew Shalliker ,&nbsp;Jake A. Cravino","doi":"10.1016/j.jpba.2026.117386","DOIUrl":"10.1016/j.jpba.2026.117386","url":null,"abstract":"<div><div>The demand for rapid and reliable analytical methods in the pharmaceutical industry continues to grow, with Ultra-/High-Performance Liquid Chromatography (U/HPLC) remaining the gold standard for impurity profiling, quantification of active pharmaceutical ingredients, and degradation product analysis. However, traditional HPLC methods are often constrained by pressure limitations at higher flow rates, which can hinder analytical throughput. While recent advancements in column technology have improved performance, they typically exacerbate pressure-related challenges. In this study, we evaluate a novel column technology designed to address these limitations by enabling high-resolution separations at reduced pressures and increased flow rates. Our findings demonstrate that the column, when operated in Radial Flow Stream Splitting (RFS) mode, maintains quantitative accuracy and repeatability while achieving up to a 120 % improvement in separation efficiency and a 30 % reduction in backpressure compared to conventional operation. By way of assaying over-the-counter medication, we have found no difference in the quantitative reliability of the assay when in RFS vs stock mode, despite reducing the analysis time by up to 40 %.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117386"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119296","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":"Corrigendum to “Integrative analysis of transcriptome and metabolome provide new insights into mechanisms of capilliposide A against cisplatin-induced nephrotoxicity” [J. Pharm. Biomed. Anal. 238 (2024), 115814]","authors":"Jiaxi Fang ,&nbsp;Luping Wang ,&nbsp;Di Zhang ,&nbsp;Yan Liang ,&nbsp;Shouxin Li ,&nbsp;Jingkui Tian ,&nbsp;Qiang He ,&nbsp;Juan Jin ,&nbsp;Wei Zhu","doi":"10.1016/j.jpba.2026.117406","DOIUrl":"10.1016/j.jpba.2026.117406","url":null,"abstract":"","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117406"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192142","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":"Simultaneous determination of three phosphatidylethanol homologues, 12 drugs and metabolites in whole blood by LC–MS/MS","authors":"Marisa H. Maria ,&nbsp;Nuno R. Neng ,&nbsp;Thomas Berg","doi":"10.1016/j.jpba.2026.117337","DOIUrl":"10.1016/j.jpba.2026.117337","url":null,"abstract":"<div><div>The use of alcohol, legal and illicit substances poses great negative consequences on health and economy worldwide. LC-MS/MS allow simultaneous determination of multiple compounds in biological matrices. The aim of this study was to develop a LC-MS/MS method for the determination of the alcohol biomarker phosphatidylethanol (PEth) – including three homologues (PEth 16:0/18:1, PEth 16:0/18:2, PEth 18:0/18:1) - cocaine and three metabolites, and 8 other drugs in whole blood. Whole blood in K2EDTA tubes was prepared by liquid-liquid extraction using heptane/ethyl acetate/2-propanol (16:64:20, v:v:v). Chromatographic separation was achieved on an Acquity BEH C₁₈ column (50 × 2.1 mm I.D., 1.7 µm particles). Mobile phase was 0.025 % ammonia, pH 10.7 (Solvent A) and methanol (Solvent B). The method was fully validated with isotope-labelled internal standards for 10 compounds. Inter-assay precision and accuracy were within ± 16 % for all analytes at five to seven tested concentrations. Recovery was within 42–79 % for 14 compounds and 11 % for benzoylecgonine. Matrix effects were within ± 25 % for most analytes. Internal standards compensated for matrix effects for compounds that had their own internal standards. A robust, precise, and accurate LC-MS/MS method for the determinations of three PEth homologues and 12 drugs and metabolites was, developed and validated. The method is valuable, especially for detecting polydrug use and alcohol consumption. To the best of our knowledge, this is the first LC-MS/MS method for the simultaneous determination of three PEth homologues and different drugs and metabolites.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117337"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180306","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":"Temperature as the primary risk factor for sevoflurane degradation: Identification and toxicological risk assessment of novel degradants by nuclear magnetic resonance (NMR) spectroscopy","authors":"Yi Jin ,&nbsp;Yaning Li ,&nbsp;Haoran Yang ,&nbsp;Huiying Yang ,&nbsp;Yaqing Guo ,&nbsp;Xianfu Wu","doi":"10.1016/j.jpba.2026.117391","DOIUrl":"10.1016/j.jpba.2026.117391","url":null,"abstract":"<div><div>Sevoflurane is an inhalation anesthetic, which is widely favored by anesthesiologists in modern clinical practice. It is reported that sevoflurane readily degrades under certain conditions. Forced degradation studies are essential for elucidating its degradation profile under stressed conditions, as recommended by the ICH guidelines. This study systematically assessed the impact of temperature, light, oxidation, and hydrolysis on sevoflurane stability through forced degradation studies. The results indicated that temperature was identified as the primary trigger for degradation, leading to the formation of four degradation products (DPs) (including the pharmacopeial-known Impurity C and three novel sevoflurane degradants H, I, and J) at 60℃ and 95℃. Light, oxidation, and hydrolysis had no significant effect under the tested conditions. The structures of all DPs were confirmed using nuclear magnetic resonance spectroscopy (NMR). Capitalizing on the inherent quantitative proficiency of this technique, we subsequently employed quantitative proton nuclear magnetic resonance spectroscopy (qHNMR) to determine the relative contents of these four DPs, which can further elucidate the degradation profile of sevoflurane. <em>In silico</em> toxicity and metabolic behavior of them were assessed by Derek Nexus and Meteor Nexus software, respectively. DPs H-J exhibited potential skin irritation/corrosion and sensitization effects across species, potentially attributable to alkyl aldehyde functional groups. All of our efforts are expected to provide guidance for the quality control and optimal storage of sevoflurane.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117391"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157363","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":"Three-dimensional high-performance liquid chromatographic determination of serine, threonine and allothreonine enantiomers in the d-amino acid oxidase deficient mice and rats","authors":"Mai Oyaide ,&nbsp;Takeyuki Akita ,&nbsp;Chiharu Ishii ,&nbsp;Yukiko Shimizu ,&nbsp;Masashi Mita ,&nbsp;Ryuichi Konno ,&nbsp;Tadashi Okamura ,&nbsp;Kenji Hamase","doi":"10.1016/j.jpba.2026.117348","DOIUrl":"10.1016/j.jpba.2026.117348","url":null,"abstract":"<div><div>The amounts of the serine (Ser), threonine (Thr) and allothreonine (aThr) enantiomers were determined in tissues (cerebrum, cerebellum, pancreas, liver and kidney) and physiological fluids (plasma and urine) of rats and mice with deficiency of <span>d</span>-amino acid oxidase (DAO). DAO is an enzyme metabolizing <span>d</span>-amino acids in mammals and has been implicated in the pathophysiology of several diseases <em>via</em> the alteration of <span>d</span>-amino acids. To determine trace levels of the amino acid enantiomers, a three-dimensional (3D) HPLC system composed of reversed-phase, anion-exchange and chiral separations was designed and utilized. Prior to the 3D-HPLC analysis, the analytes were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole to enhance the fluorescence detection sensitivity. By using the 3D-HPLC system, the tissues and physiological fluids of F344-<em>Dao</em>^{<em>ldao</em>} rats and B6DAO^-/- mice (animals with the DAO deficiency) were analyzed. In both species, <span>d</span>-Ser levels were elevated in the absence of DAO activity except for the cerebrum. The amounts of <span>d</span>-Thr and <span>d</span>-aThr were increased in the cerebellum and kidney with the DAO deficiency while their amounts were almost the same in the other tissues and physiological fluids. These results indicated that the intrinsic <span>d</span>-Ser analogues were metabolized by DAO in mammals and further studies to clarify its physiological significance are expected.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117348"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142845","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":"In memoriam of Professor Sándor Görög","authors":"","doi":"10.1016/j.jpba.2026.117395","DOIUrl":"10.1016/j.jpba.2026.117395","url":null,"abstract":"","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117395"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157390","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 validation of a sensitive and rapid UHPLC-MS/MS method for the simultaneous quantification of CG-0255 and its active metabolite in human plasma and its application to Phase I studies","authors":"Hanjing Chen ,&nbsp;Jiali Li ,&nbsp;Fei Yuan ,&nbsp;Gongxin He ,&nbsp;Hao Wu ,&nbsp;Hua Yan ,&nbsp;Hongrong Xu ,&nbsp;Chao Liu ,&nbsp;Lei Sheng ,&nbsp;Xuening Li","doi":"10.1016/j.jpba.2026.117390","DOIUrl":"10.1016/j.jpba.2026.117390","url":null,"abstract":"<div><div>CG-0255, a thiol prodrug of clopidogrel’s active metabolite H4 (CG-0236), is a novel thienopyridine P2Y12 receptor antagonist under initial clinical development for the treatment of acute coronary syndromes. Unlike clopidogrel, CG-0255 is converted to the active thiol metabolite H4 (CG-0236) in a single hydrolytic step. Compared with clopidogrel, CG-0255 exhibits more efficient and consistent H4 formation in humans, which can be quantified in plasma following either intravenous or oral administration. In this study, we developed and validated a sensitive, rapid, and robust UHPLC–MS/MS method for the simultaneous quantification of CG-0255 and its derivatized active metabolite (MP-H4, CG-0261) in human plasma. After solid-phase extraction from 94.5 μL of plasma, analytes and isotope-labeled internal standards were separated on an ACQUITY UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) using isocratic elution with 0.1 % formic acid in water and acetonitrile (57:43, v/v) at a flow rate of 0.5 mL/min, followed by a 3.5 min column washing and re-equilibration, giving a total analytical run time of 7 min. Baseline separation of CG-0255, CG-0261, and their respective isomers was achieved. Detection was performed using positive electrospray ionization in multiple reaction monitoring mode on a Q-Trap 6500⁺ mass spectrometer. Calibration curves were linear over 0.05–25 ng/mL for both analytes, corresponding to 0.0353–17.65 ng/mL for H4 (CG-0236). Intra- and inter-day precision and accuracy were within ±15 % at all quality-control levels. The validated assay was successfully applied to two phase I clinical studies conducted at our center, characterizing the pharmacokinetics of CG-0255 following single-dose intravenous and multiple-dose oral administration. This UHPLC–MS/MS method provides a reliable platform for the quantitative evaluation of CG-0255 and its active metabolite in human plasma, and is well suited to support further global clinical development.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117390"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132099","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 streamlined workflow for early phase formulation development of monoclonal antibodies comprising multi-attribute method and ligand binding assay","authors":"Rachel Smith ,&nbsp;Colin Guy ,&nbsp;Rosie Upton ,&nbsp;Sam Clawson ,&nbsp;Henry Fisher ,&nbsp;Mohammad Adam Nasar ,&nbsp;David Firth ,&nbsp;Allan Watkinson","doi":"10.1016/j.jpba.2026.117379","DOIUrl":"10.1016/j.jpba.2026.117379","url":null,"abstract":"<div><div>A streamlined early phase formulation development workflow has been developed for monoclonal antibodies (mAbs) to provide a more efficient process, driving down costs and reducing timelines, without compromising the quality and hence patient safety. The proposed novel workflow combines liquid chromatography-mass spectrometry multi-attribute method (LC-MS MAM) and sensitive ligand binding using surface plasmon resonance (SPR). By linking the two methodologies it is possible to obtain a comprehensive understanding of a mAb’s critical quality attributes (CQAs) and provide a structure/function correlation. As LC-MS MAM cannot address all aspects of degradation, high throughput methods for the analysis of high molecular weight material (HMWM), and conformational and colloidal stability, were also evaluated. The workflow comprises an initial forced degradation study, to verify stability-indication and identify potential degradation routes. Secondly, optimal pH, based on conformational and colloidal stability, is determined. Finally, stabilising excipients are evaluated by design of experiment (DoE). We have verified this workflow using pembrolizumab. In an initial forced degradation study, LC-MS MAM and PD-1 ligand binding could identify the CQAs. Met105 oxidation, located in the CDR3 region, was identified as the major CQA. DoE demonstrated that 25 mM methionine inhibited Met105 oxidation and stabilised PD-1 binding. With this streamlined process, we were able to improve the stability of the protein by formulating in 20 mM histidine, 25 mM methionine, 0.02 % PS80 and 300 mM sucrose, at pH 5.5. The described workflow has the potential to decrease the demand for precious early development material as well as reduce costs and shorten timelines.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"273 ","pages":"Article 117379"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132126","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}