Rapid Communications in Mass Spectrometry最新文献

{"title":"The Possibility of X-Type Ions With Linear Saturated Non-Reducing Termini Dissociated From Potasiated Saikosaponins","authors":"Guoqiang Liu,&nbsp;Yuexi Yang","doi":"10.1002/rcm.70128","DOIUrl":"https://doi.org/10.1002/rcm.70128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>MS dissociation of potassiated parent ions may play an important role in the structural characterization for some compounds but was seldom reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four isomeric saikosaponins, i.e., a, d, b1, and b2, were characterized through LC/IT-TOFMS analysis in the positive ionization mode. And their [M + H + K]²⁺ and [M + K]⁺ ions were selected for further dissociation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here was presented the first report of the mass dissociation of potasiated saikosaponins, i.e., [M + H + K]²⁺ and [M + K]⁺, both of which, according to our cautious analysis, produced the potasiated X-type ions with linear, saturated nonreducing termini.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The potasiated rather than sodiated saikosaponins gave informative A- and X-type fragment ions. The speculative potasiated X-type ions with linear, saturated nonreducing termini were not reported previously as far as we knew, which may make an essential complement to the current knowledge of mass fragmentation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 18","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Humidity on Ionisation and Ion Chemistry in Active-Capillary Dielectric Barrier Discharge Ionisation","authors":"Miroslav Polášek,&nbsp;Patrik Španěl,&nbsp;Kseniya Dryahina","doi":"10.1002/rcm.70130","DOIUrl":"https://doi.org/10.1002/rcm.70130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Dielectric barrier discharge ionisation (DBDI) in an active-capillary configuration (including the commercial SICRIT source) is widely used as a soft, ambient-pressure ionisation method for vapours and gases, yet the role of water vapour in controlling reagent ion chemistry and analytical behaviour has not been mechanistically described. Thus, it is necessary to understand how carrier gas humidity governs reagent ion populations and product ion formation in a DBDI source.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A SICRIT ion source was coupled to a triple-quadrupole mass spectrometer and operated under constant discharge conditions while switching the carrier gas between humidified and nominally dry air. Ketones and short-chain carboxylic acids were introduced at trace vapour concentrations using permeation or diffusion tubes. Reagent ion and analyte mass spectra were acquired in full-scan mode. Selected analyte ions were subjected to collision-induced dissociation (CID) to compare in-source fragments with those formed from protonated molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Under humid conditions, the reagent ion population was dominated by hydrated hydronium ions. Analytes yielded mainly protonated molecules, MH⁺ and their hydrates, with minimal fragmentation. Switching to a dry carrier gas reduced the total ion current by more than an order of magnitude and led to extensive, structure-dependent fragmentation. Comparison with CID spectra of MH⁺ indicates that the fragments observed under dry conditions arise from the fragmentation of protonated molecules rather than from the direct dissociation of radical cations. This is explained by highly exothermic proton transfer from a dominant <i>m/z</i> 29 reagent ion (most plausibly N₂H⁺).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results highlight humidity as a key operational active-capillary DBDI parameter; varying it enables both low-fragmentation ionisation in humid mode and more energetic fragmenting ionisation in dry mode. The humid mode facilitates reproducible quantitation, whereas the dry mode allows structural discrimination, exemplified by differentiation of hexanone isomers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 18","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rcm.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal Transformer Fusion of PTR-ToF-MS Volatiles and Targeted Non-Volatile Metabolites Enables Data-Driven Grading of Baimudan White Tea","authors":"Dandan Zhang,&nbsp;Suk-Hwan Hong,&nbsp;Xiaojing Li","doi":"10.1002/rcm.70122","DOIUrl":"https://doi.org/10.1002/rcm.70122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Commercial grading of Baimudan white tea still relies largely on sensory evaluation and would benefit from a rapid, objective analytical approach. This study investigated whether PTR-ToF-MS volatile fingerprints combined with targeted non-volatile metabolite measurements could support data-driven grading of four official Baimudan grades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Headspace volatiles were profiled by proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS), and non-volatile metabolites were quantified by HPLC, amino acid analysis, and soluble sugar assay. A total of 120 samples (30 per grade) were divided into a training set (<i>n</i> = 96) and an independent prediction set (<i>n</i> = 24). A two-stream Transformer encoded the volatile and non-volatile modalities separately and fused them for four-class classification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The multimodal model achieved 95.8% accuracy (23/24) and a macro-F1 score of 0.958 on the independent prediction set, with a single misclassification between adjacent high grades. Repeated stratified five-fold cross-validation within the training set showed stable performance. SHAP and attention analyses indicated that high-grade teas were associated with floral/sweet volatile ions and higher amino acids and soluble sugars, whereas lower grades were associated with greener/woody volatile ions and kaempferol-related markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Within the current dataset, integrating PTR-ToF-MS volatile fingerprints with targeted non-volatile metabolites provides an objective and chemically interpretable approach for instrument-assisted grading of Baimudan white tea.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 18","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rcm.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of Residual Nitrilase in Brivaracetam Using Characteristic Peptides by Liquid Chromatography–Mass Spectrometry","authors":"Xueting Dai,&nbsp;Kongliang Xu,&nbsp;Tianji Zhang,&nbsp;Ming Li,&nbsp;Peize Wu,&nbsp;Jinlan Cheng,&nbsp;Hanrui Chen","doi":"10.1002/rcm.70126","DOIUrl":"10.1002/rcm.70126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Nitrilases are widely used as biocatalysts in pharmaceutical manufacturing because of their high stereoselectivity and mild reaction conditions. However, residual nitrilase in final drug products may compromise product quality and safety, highlighting the need for sensitive and reliable analytical methods for its monitoring and control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the determination of residual nitrilase in pharmaceutical formulations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Recombinant nitrilase expressed in <i>Escherichia coli</i> was purified by Ni²⁺ affinity chromatography and lyophilized prior to analysis. Following systematic optimization of digestion and chromatographic conditions, the method achieved a detection limit of 0.17 μg/g. The LC–MS/MS method was successfully applied to the analysis of brivaracetam samples at a concentration of 2000 μg/g, with residual nitrilase levels consistently below 85 μg/g, meeting relevant quality control requirements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this study, a sensitive and reliable LC–MS/MS method was developed for the determination of residual nitrilase in brivaracetam. The proposed method may serve as a general analytical strategy for quality control of nitrilase-related pharmaceutical products.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 17","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioanalysis of Ametryn by UHPLC-MS3 Coupled With Multiple Fragmentation to Decrease Interference and Enhance Sensitivity","authors":"Yue Deng,&nbsp;Hongjie Ju,&nbsp;Fangyu Liu,&nbsp;Jiarui Zhang,&nbsp;Shuang Feng,&nbsp;Jiale Liu,&nbsp;Xinyue Zhou,&nbsp;Lei Yin,&nbsp;Meiyun Shi","doi":"10.1002/rcm.70124","DOIUrl":"10.1002/rcm.70124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Ametryn poses significant risks to aquatic ecosystems, but conventional MRM methods suffer from matrix interference and limited sensitivity. To overcome these limitations, we established a more selective and sensitive UHPLC-MS³ approach that effectively suppresses background noise and enhances signal-to-noise ratio, enabling reliable quantification of ametryn in zebrafish tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A novel UHPLC-MS³ method with electrospray ionization was developed. Quantification employed the MS³ transition <i>m/z</i> 228.0 → 186.1 → 158.0. Five zebrafish tissues (liver, muscle, brain, intestine, gill) were analyzed following sample preparation. Fast chromatographic separation was achieved in 2.8 min.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with MRM, the MS³ method substantially reduced matrix interference, enhanced signal intensity from 6.4 × 10⁴ to 1.6 × 10⁷ cps, and increased the signal-to-noise ratio from 6.3 to 45. The assay exhibited excellent linearity (10–1000 pg/mL), and validation results for accuracy, precision, recovery, matrix effects, and stability all met FDA bioanalytical requirements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study presents the first application of UHPLC-MS³ for quantitative analysis of ametryn in multiple zebrafish tissues, providing a reliable high-throughput platform for residue monitoring and mechanistic toxicology research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 17","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Structurally Related Impurity Profiles in Teriparatide From Synthetic and Recombinant DNA Origin Using Liquid Chromatography–High Resolution Mass Spectrometry","authors":"Peize Wu,&nbsp;Yuya Cheng,&nbsp;Dagang Li,&nbsp;Haocun Tan,&nbsp;Jinying Li,&nbsp;Dongxiang Zhang","doi":"10.1002/rcm.70125","DOIUrl":"10.1002/rcm.70125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Teriparatide (TPT) is a synthetic peptide primarily used in the clinical treatment of osteoporosis, with its reference materials available from both synthetic and recombinant DNA origin used for generic drug preparations. Considering the potential toxicological effects of structurally related impurities, systematic characterisation of the impurity profiles of TPT reference materials arising from different synthetic sources is essential for regulatory evaluations of generic drugs' safety and efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One commercially available chemical synthesis material and two recombinant synthesis pharmacopoeia reference standards were used to investigate the TPT impurity profiles in this study. Separation for the structurally related impurities was achieved via liquid chromatography, and mass spectrometry analysis was conducted by electro-spray ionization linear quadrupole ion trap-Orbitrap mass spectrometry. Subsequently, external standard method and four quantitative scenarios were adopted to achieve an accurate quantification of structurally related impurities in the TPT study materials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Distinct impurity profiles were observed in the TPT study materials from different synthetic sources. One isomer and three oxidation impurities were found co-existing in all the study materials. Six amino acid deletion impurities were specifically observed and identified in chemically synthetic TPT material. Among these detected impurities, eight impurities were newly characterized in addition to the previous studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A liquid chromatography–high resolution mass spectrometry–based method was developed for the identification and quantification of structurally related impurities in three TPT study materials from different synthetic sources. Characterization of these TPT impurity profiles highlights the necessity of synthetic source-specific impurity monitoring for TPT production and contributes to enhanced regulatory evaluation of generic peptide drugs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 17","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Stability and Metabolic Profile of Schisandrol B in Rat and Human Liver Microsomes Employing HPLC-MS/MS Analysis","authors":"Tao Hu,&nbsp;Yicong Bian,&nbsp;Sheng Ma,&nbsp;Linsheng Liu,&nbsp;Qingqing Deng,&nbsp;Liyan Miao","doi":"10.1002/rcm.70127","DOIUrl":"10.1002/rcm.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Schisandrol B (Sol B) is a major bioactive lignan compound extracted from the dried fruits of <i>Schisandra chinensis</i> (Turcz.) Baill. with comprehensive pharmacological activities. The study aims to investigate the metabolic stability and metabolic characteristics of Sol B in rat liver microsomes (RLMs) and human liver microsomes (HLMs) and further clarify the metabolic differences among different species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>The in vitro incubation systems included 5 μM Sol B and 0.5 mg/mL HLMs or RLMs in the presence of NADPH (5 mM) at 37°C in 200 μL phosphate-buffered saline. The residual amount of Sol B in the incubation system at different time points was determined to calculate the metabolic stability. The main metabolites of Sol B were identified and further elucidated the main metabolic pathways of Sol B.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After incubation in RLMs and HLMs for 60 min, the remaining percentage of parent drug was 26.42% and 55.04%, and the <i>t</i>_<i>1/2</i> was calculated as 33.6 min and 75.21 min, respectively. A total of seven metabolites were detected in RLMs and HLMs systems. Metabolites M402-1 and M384-1 were detected only in the RLMs incubation system, while all other metabolites were monitored in both RLMs and HLMs incubation systems. Main metabolic pathways of Sol B in RLMs and HLMs mainly include dehydration, O-demethylation, and oxidative dehydrogenation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The metabolic behavior of Sol B in RLMs and HLMs exhibited certain species differences. Overall, Sol B was more stable in HLMs, with relatively simpler metabolic pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 17","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stable Isotope Composition of Skin Layers Confirms Trophic Differentiation of Baird's and Sato's Beaked Whales (Berardius spp.) in the Western North Pacific","authors":"Olga A. Filatova,&nbsp;Ivan D. Fedutin,&nbsp;Igor G. Bobyr,&nbsp;Olga V. Titova,&nbsp;Mikhail O. Ragimov,&nbsp;Erich Hoyt,&nbsp;Sergey M. Tsurikov,&nbsp;Alexei V. Tiunov","doi":"10.1002/rcm.70123","DOIUrl":"10.1002/rcm.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Closely related whale species can appear similar yet occupy distinct ecological niches. Sato's beaked whale (<i>Berardius minimus</i>) was only recently recognized as a separate species and was previously grouped with Baird's beaked whale (<i>Berardius bairdii</i>), limiting our understanding of their ecological differences. Clarifying their trophic ecology is essential for accurate species-specific conservation and management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Skin biopsy and necropsy samples of <i>B. bairdii</i> and <i>B. minimus</i> were collected in the western North Pacific in 2017–2025. Carbon (δ¹³C) and nitrogen (δ¹⁵N) stable isotope ratios were measured from three separately analyzed epidermal layers of skin samples using isotope ratio mass spectrometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>B. bairdii</i> exhibited significantly higher δ¹³C values than <i>B. minimus</i>, whereas δ¹⁵N values were broadly similar, indicating comparable trophic positions but distinct foraging habitats. Higher δ¹³C values in <i>B. bairdii</i> suggest greater reliance on benthic or coastal food webs, whereas lower δ¹³C values in <i>B. minimus</i> reflect stronger associations with offshore ecosystems. Isotopic variation of different epidermal layers revealed temporal dietary shifts within individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results demonstrate clear ecological differentiation between <i>B. bairdii</i> and the recently described <i>B. minimus</i>. Historical data attributed to <i>B. bairdii</i> should be re-evaluated to ensure accurate species-specific interpretations of diet and habitat use, improving ecological understanding and conservation assessments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 17","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rcm.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality by Design-Assisted Separation and Characterization of Photolytic Degradation Products of Midostaurin Using UHPLC-Q-TOF-MS/MS: In-Silico Prediction and Toxicity Assessment","authors":"Rupali Mahajan,&nbsp;Saurabh Shah,&nbsp;Saurabh Srivastava,&nbsp;Amit Asthana,&nbsp;Gananadhamu Samanthula","doi":"10.1002/rcm.70120","DOIUrl":"10.1002/rcm.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Midostaurin is the first-in-class antineoplastic agent for acute myeloid leukemia (AML), exhibits a distinctive pyrrolo[2,3-b]pyridine scaffold, and is susceptible to forming five forced degradation products under photolytic conditions. Impurities in products can compromise their safety and efficacy, often leading to significant recalls. Hence, strict quality control and reliable analytical methods are essential to prevent these risks. To the best of our knowledge, the lack of available literature on midostaurin in photolytic stress conditions drives the rationale for this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The current study described a quality-by-design approach for developing a robust RP-HPLC analytical methodology. Simultaneously, we devised a rapid UHPLC technique that is transferable for LC–MS analysis to characterize DPs within a 6-min period using LC-Q-TOF-MS/MS. In QbD, a Taguchi orthogonal array design was employed for screening the significant factors, i.e., column temperature, buffer pH, and flow rate. A Box–Behnken design was employed to study the interactions of the chosen factors on the tailing factor and resolution of the analyte and five DPs. Additionally, Zeneth software was used to estimate photolytic DPs. Further, the study was extended using Derek and Sarah software to determine toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Midostaurin was found to form five degradation products under photolytic stress conditions. Four degradation products (DP-2, DP-3, DP-4, and DP-5; <i>m/z</i> 587, <i>m/z</i> 546, and <i>m/z</i> 585) were structurally characterized using LC-Q-TOF-MS/MS, whereas DP-1 was detected as an unidentified degradation peak due to a lack of ionization. Partial agreement was observed between Zeneth predictions and experimental findings. In silico toxicity assessment using Derek and Sarah software provided preliminary safety insights for the characterized degradation products.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study demonstrates the development of a QbD-based RP-HPLC and UHPLC-LC–MS method for the analysis of photolytic degradation products of midostaurin. The approach enables effective impurity profiling and provides supportive insights into degradation behavior and toxicity, contributing to improved quality control.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 17","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the Potential Mechanism of Clematichinenoside AR in Alleviating Hyperuricemia Based on Untargeted Metabolomics and Nrf2 Signaling Pathway","authors":"Qi Liang,&nbsp;Heng Lu,&nbsp;Hongjing Dong,&nbsp;Jinqian Yu,&nbsp;Tao Li,&nbsp;Xiao Wang,&nbsp;Yanyan Zhang","doi":"10.1002/rcm.70109","DOIUrl":"10.1002/rcm.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Hyperuricemia (HUA) is a metabolic disorder commonly accompanied by oxidative stress and inflammatory responses, which contribute to the progression of kidney and liver injury. Clematichinenoside AR (C-AR), a natural triterpenoid saponin, has been reported to regulate metabolism and exert anti-inflammatory and antioxidant activities. However, its therapeutic potential and underlying mechanisms in HUA remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The anti-hyperuricemic effect of C-AR was evaluated in a mouse model of HUA. Biochemical assays and histopathological analyses were performed to assess uric acid metabolism and organ injury. The expression of inflammation-, oxidative stress-, and urate transport-related factors was determined by RT-qPCR and Western blotting. Untargeted serum metabolomics was conducted using UPLC-Q-TOF-MS/MS to investigate metabolic alterations associated with C-AR treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>C-AR significantly reduced serum uric acid levels, inhibited xanthine oxidase activity, and alleviated uric acid-induced kidney and liver injury. It suppressed inflammatory responses by decreasing TNF-α, IL-6, and IL-1β levels and attenuated oxidative stress by reducing renal malondialdehyde levels. Furthermore, C-AR upregulated ABCG2, NRF2, and HO-1 expression while downregulating NLRP3 and Caspase-1. Untargeted metabolomics revealed that C-AR predominantly regulated purine metabolism and restored metabolic disturbances associated with HUA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>C-AR effectively ameliorates hyperuricemia by regulating uric acid metabolism, suppressing inflammation, and alleviating oxidative stress. These effects are associated with modulation of the NRF2/HO-1 signaling pathway and purine metabolism, supporting the potential development of C-AR as a natural therapeutic agent for hyperuricemia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 17","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}