Alan M. Rowland, Stephen E. Smith, Ella F. Vandergriff, Arturo Rodriguez, David P. Lewis, Kevin P. Schultze, William M. Gilliland Jr.
With the goal of sensitive, selective, targeted, and portable VOC quantification, an atmospheric pressure photoionization (APPI) source was developed for a miniature high pressure mass spectrometer, the MX908. The APPI source consists of a VUV lamp that was encased in a custom 3D-printed apparatus. Using m-xylene as the testing standard, the effects of pressure, axial RF voltage, aperture voltage, and humidity on the instrument were investigated and optimized. Operating at 0.8 Torr with ambient air as the buffer gas, the instrument showed linearity from 25 to 500 ppbV for benzene, toluene, ethylbenzene, and m-xylene without preconcentration.
{"title":"Development of an Atmospheric-Pressure Photoionization Source for VOC Detection With a Miniature High-Pressure Mass Spectrometer","authors":"Alan M. Rowland, Stephen E. Smith, Ella F. Vandergriff, Arturo Rodriguez, David P. Lewis, Kevin P. Schultze, William M. Gilliland Jr.","doi":"10.1002/rcm.70050","DOIUrl":"10.1002/rcm.70050","url":null,"abstract":"<p>With the goal of sensitive, selective, targeted, and portable VOC quantification, an atmospheric pressure photoionization (APPI) source was developed for a miniature high pressure mass spectrometer, the MX908. The APPI source consists of a VUV lamp that was encased in a custom 3D-printed apparatus. Using <i>m</i>-xylene as the testing standard, the effects of pressure, axial RF voltage, aperture voltage, and humidity on the instrument were investigated and optimized. Operating at 0.8 Torr with ambient air as the buffer gas, the instrument showed linearity from 25 to 500 ppbV for benzene, toluene, ethylbenzene, and <i>m</i>-xylene without preconcentration.</p>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12875154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111603","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}
Amoxicillin is a broad-spectrum β-lactam antibiotic that is prone to undergo degradation under various stress and storage conditions into multiple impurities, which may compromise drug stability, efficacy, and safety. This study established an eco-efficient comprehensive analytical strategy for amoxicillin degradation impurities using UHPLC coupled with PDA detection and QTOF-MS characterization, which has not been previously reported.
Methods
Chromatographic conditions were optimized through software-assisted conversion from traditional chromatography and then validated for the simultaneous determination of degradation impurities. Separation was performed on a Cortecs C18 column (150 × 3 mm; 2.7 μm) at 254 nm with a gradient elution of acetonitrile and a pH 5.0 buffer solution. Degradation products were identified and characterized using UHPLC-PDA/Q/TOF-MS. The environmental impact of the method was evaluated using the Eco-Scale, GAPI, AGREE, and BAGI tools.
Results
The validated method in accordance with ICH Q2(R2) (2023) demonstrates system suitability, specificity, linearity (3.003–22.519 μg/mL), accuracy (98.0%–102%, RSD < 2.0%), precision (RSD < 2.0%), and robustness. Limits of detection and quantification were 0.330 and 0.991 μg/mL, respectively, enabling the quantification of impurities at 0.066% relative to amoxicillin content in 500-mg capsules. Four degradation impurities exceeding the identification thresholds were characterized, including amoxicillin diketopiperazine, penilloic acid, and two newly detected compounds not listed in the current international pharmacopoeias. Greenness evaluation tools confirm the environmental friendliness of the method, with high scores of 78 (Eco-Scale), 80 (BAGI), 68 (GAPI), and 0.63 (AGREE).
Conclusions
The study delivers enhanced chromatographic resolution for understanding the degradation pathways of amoxicillin during short- and long-term storage, enabling stability evaluation and routine drug quality control in accordance with sustainable development goals.
{"title":"A Sustainable UHPLC-PDA/QTOF-MS Approach for Comprehensive Profiling of Amoxicillin Degradation Impurities","authors":"Vo Thi Kim Khuyen, Do Thanh Nhu, Nguyen Duc Tuan","doi":"10.1002/rcm.70046","DOIUrl":"10.1002/rcm.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Amoxicillin is a broad-spectrum β-lactam antibiotic that is prone to undergo degradation under various stress and storage conditions into multiple impurities, which may compromise drug stability, efficacy, and safety. This study established an eco-efficient comprehensive analytical strategy for amoxicillin degradation impurities using UHPLC coupled with PDA detection and QTOF-MS characterization, which has not been previously reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Chromatographic conditions were optimized through software-assisted conversion from traditional chromatography and then validated for the simultaneous determination of degradation impurities. Separation was performed on a Cortecs C18 column (150 × 3 mm; 2.7 μm) at 254 nm with a gradient elution of acetonitrile and a pH 5.0 buffer solution. Degradation products were identified and characterized using UHPLC-PDA/Q/TOF-MS. The environmental impact of the method was evaluated using the Eco-Scale, GAPI, AGREE, and BAGI tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The validated method in accordance with ICH Q2(R2) (2023) demonstrates system suitability, specificity, linearity (3.003–22.519 μg/mL), accuracy (98.0%–102%, RSD < 2.0%), precision (RSD < 2.0%), and robustness. Limits of detection and quantification were 0.330 and 0.991 μg/mL, respectively, enabling the quantification of impurities at 0.066% relative to amoxicillin content in 500-mg capsules. Four degradation impurities exceeding the identification thresholds were characterized, including amoxicillin diketopiperazine, penilloic acid, and two newly detected compounds not listed in the current international pharmacopoeias. Greenness evaluation tools confirm the environmental friendliness of the method, with high scores of 78 (Eco-Scale), 80 (BAGI), 68 (GAPI), and 0.63 (AGREE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study delivers enhanced chromatographic resolution for understanding the degradation pathways of amoxicillin during short- and long-term storage, enabling stability evaluation and routine drug quality control in accordance with sustainable development goals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099710","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}
Isaure Sergent, Ian Roszak, Jean-François Lutz, Laurence Charles
Rationale
MS/MS sequencing is commonly used to read binary messages encoded in digital polymers. To achieve full sequence coverage required for error-free reading, the structure of coding units is usually optimized to prevent extensive signal dilution over multiple fragmentation routes. Changing ionization polarity can also have a significant effect on MS/MS pattern, which is explored here for poly(amino phosphodiester)s.
Methods
Poly(amino phosphodiester)s (N-PPDEs) include comonomers composed of one phosphate group and a main-chain tertiary amine holding different alkyl substituents as coding moieties. Accordingly, they can be readily ionized in both polarity modes, using ammonium acetate to promote electrospray formation of deprotonated species and protonated molecules when switching from negative to positive ion mode. Changes of their MS/MS spectra are studied with regard to the behavior of their PPDE homologues lacking the main-chain tertiary amine.
Results
In collision-induced dissociation (CID) conditions, eight fragment series are produced upon cleavage of all phosphate bonds in deprotonated species, whereas only four ion series are generated from protonated N-PPDEs in which O–P–O linkages remain intact. The advantageous MS/MS behavior of protonated N-PPDEs has been rationalized by considering that protons located on tertiary amines are also solvated by nearby phosphate groups, promoting exclusive cleavage of C–O bonds.
Conclusions
In contrast to PPDEs, switching from deprotonated to protonated precursors yields highly simplified CID data for N-PPDEs, opening promising perspectives for reliable MS/MS sequencing of long coded polymers.
{"title":"Switching Ionization Polarity to Simplify MS/MS Sequencing of Digital Polymers: the Case of Informational Poly(Amino phosphodiester)s","authors":"Isaure Sergent, Ian Roszak, Jean-François Lutz, Laurence Charles","doi":"10.1002/rcm.70047","DOIUrl":"10.1002/rcm.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>MS/MS sequencing is commonly used to read binary messages encoded in digital polymers. To achieve full sequence coverage required for error-free reading, the structure of coding units is usually optimized to prevent extensive signal dilution over multiple fragmentation routes. Changing ionization polarity can also have a significant effect on MS/MS pattern, which is explored here for poly(amino phosphodiester)s.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Poly(amino phosphodiester)s (N-PPDEs) include comonomers composed of one phosphate group and a main-chain tertiary amine holding different alkyl substituents as coding moieties. Accordingly, they can be readily ionized in both polarity modes, using ammonium acetate to promote electrospray formation of deprotonated species and protonated molecules when switching from negative to positive ion mode. Changes of their MS/MS spectra are studied with regard to the behavior of their PPDE homologues lacking the main-chain tertiary amine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In collision-induced dissociation (CID) conditions, eight fragment series are produced upon cleavage of all phosphate bonds in deprotonated species, whereas only four ion series are generated from protonated N-PPDEs in which O–P–O linkages remain intact. The advantageous MS/MS behavior of protonated N-PPDEs has been rationalized by considering that protons located on tertiary amines are also solvated by nearby phosphate groups, promoting exclusive cleavage of C–O bonds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In contrast to PPDEs, switching from deprotonated to protonated precursors yields highly simplified CID data for N-PPDEs, opening promising perspectives for reliable MS/MS sequencing of long coded polymers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099746","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}
Bushen Huoxue (BSHX) decoction is effective against intervertebral disc degeneration (IVDD) and osteoarthritis, but its mechanism remains unclear. This study investigates its potential role in regulating efferocytosis in IVDD.
Methods
BSHX decoction, prepared from Eucommia ulmoides, Psoralea corylifolia, Achyranthes bidentata, Salvia miltiorrhiza, Clematis chinensis, and Chaenomeles speciosa, was extracted, concentrated, and analyzed by LC–MS/MS to identify active ingredients. Swiss TargetPrediction analysis predicted all targets. The PPI network was constructed using STRING 12.0 and CytoNCA in Cytoscape, followed by GO and KEGG enrichment analyses. Three publicly available datasets (GSE70362, GSE124272, GSE150408) were analyzed for differential gene expression in IVDD, with efferocytosis-related genes retrieved from GeneCards and KEGG, and candidate targets identified by intersecting PPI network core targets with efferocytosis-related differentially expressed genes (EFRDEGs). A network pharmacology model was then constructed, followed by molecular docking, molecular dynamics simulations, and pharmacokinetic properties.
Results
A total of 77 active ingredients and 298 targets were identified, with ELANE, MPO, and RXRA selected as candidate targets through bioinformatics analysis. GO and KEGG analyses highlighted their roles in immune regulation, inflammation, apoptosis, and tissue repair. Network analysis suggests that these compounds regulate multiple pathways, providing a mechanism for BSHX decoction to alleviate IVDD by modulating efferocytosis. Molecular docking showed strong binding affinity (binding energy < −8.0 kcal/mol) of tanshinone II A, pinoresinol diglucoside, and psoralidin with ELANE, MPO, and RXRA. Molecular dynamics simulation of the MPO–pinoresinol diglucoside complex confirmed its stability, and we revealed that pinoresinol diglucoside possesses favorable pharmacokinetic properties and safety characteristics.
Conclusion
BSHX decoction may exert therapeutic effects on IVDD by targeting ELANE, MPO, and RXRA to regulate multiple pathways involved in efferocytosis. These findings offer valuable insights into the underlying mechanisms of BSHX decoction in the treatment of IVDD, providing a solid theoretical basis for the clinical application of traditional Chinese medicine.
{"title":"Exploring the Mechanistic Role of Bushen Huoxue Decoction in Treating Intervertebral Disc Degeneration Through Efferocytosis Regulation","authors":"Hongtao Li, Changxiao Han, Jiacheng Zheng, Zhiwen Li, Xu Wang, Liguo Zhu, Minshan Feng","doi":"10.1002/rcm.70043","DOIUrl":"10.1002/rcm.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bushen Huoxue (BSHX) decoction is effective against intervertebral disc degeneration (IVDD) and osteoarthritis, but its mechanism remains unclear. This study investigates its potential role in regulating efferocytosis in IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>BSHX decoction, prepared from <i>Eucommia ulmoides</i>, <i>Psoralea corylifolia</i>, <i>Achyranthes bidentata</i>, <i>Salvia miltiorrhiza</i>, Clematis chinensis, and <i>Chaenomeles speciosa</i>, was extracted, concentrated, and analyzed by LC–MS/MS to identify active ingredients. Swiss TargetPrediction analysis predicted all targets. The PPI network was constructed using STRING 12.0 and CytoNCA in Cytoscape, followed by GO and KEGG enrichment analyses. Three publicly available datasets (GSE70362, GSE124272, GSE150408) were analyzed for differential gene expression in IVDD, with efferocytosis-related genes retrieved from GeneCards and KEGG, and candidate targets identified by intersecting PPI network core targets with efferocytosis-related differentially expressed genes (EFRDEGs). A network pharmacology model was then constructed, followed by molecular docking, molecular dynamics simulations, and pharmacokinetic properties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 77 active ingredients and 298 targets were identified, with ELANE, MPO, and RXRA selected as candidate targets through bioinformatics analysis. GO and KEGG analyses highlighted their roles in immune regulation, inflammation, apoptosis, and tissue repair. Network analysis suggests that these compounds regulate multiple pathways, providing a mechanism for BSHX decoction to alleviate IVDD by modulating efferocytosis. Molecular docking showed strong binding affinity (binding energy < −8.0 kcal/mol) of tanshinone II A, pinoresinol diglucoside, and psoralidin with ELANE, MPO, and RXRA. Molecular dynamics simulation of the MPO–pinoresinol diglucoside complex confirmed its stability, and we revealed that pinoresinol diglucoside possesses favorable pharmacokinetic properties and safety characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BSHX decoction may exert therapeutic effects on IVDD by targeting ELANE, MPO, and RXRA to regulate multiple pathways involved in efferocytosis. These findings offer valuable insights into the underlying mechanisms of BSHX decoction in the treatment of IVDD, providing a solid theoretical basis for the clinical application of traditional Chinese medicine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083666","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}
Jianglan Long, Yueyue Wang, Qiushi Fang, Zhe Shi, Zhenzhen Wang, Dan Yan
Rationale
Over 70% of diabetic patients die from cardiovascular disease, in which diabetic heart disease (DHD) is an important cause of death in individuals with type 2 diabetes (T2D). It is hence imperative to explore the simple, rapid, and economical method for diagnosing DHD from T2D.
Methods
T2D and DHD patients were recruited, and their serum samples were used for metabolomic analysis to identify differential metabolites. Logistic regression analysis and receiver operating characteristic curve analysis were performed to identify candidate biomarkers. Moreover, four machine learning methods were used to construct the integrated biomarker profiling (IBP) models with the candidate biomarkers. Gini impurity was employed to select characteristic candidate biomarkers.
Results
Eighty-four differential metabolites were identified in the serum of 58 T2D and 62 DHD patients. Logistic regression analysis indicated that 17 differential metabolites were protective factors, whereas 39 were risk factors for DHD. Further, 29 differential metabolites were identified as the candidate biomarkers of DHD after receiver operating characteristic curve analysis. After comparing the predictive performance of the four machine learning models, the IBP was constructed based on the eXtreme Gradient Boosting (XGBoost) with six candidate biomarkers, which were sphingomyelin (d18:0/16:1), deoxycholic acid, hexadecanedioic acid, phosphatidylcholine (20:5/18:3), L-tryptophan, and N-undecanoylglycine from the ranked results of Gini impurity. The accuracy of the IBP for distinguishing T2D and DHD reached 88.89%, with a 100% accuracy in predicting DHD from T2D patients.
Conclusions
The IBP, composed of six metabolites, can effectively predict DHD from T2D, and it is expected to become a screening indicator for early-stage DHD.
{"title":"UHPLC-Q-Orbitrap HRMS-Based Machine Learning Constructs the Integrated Biomarker Profiling of Type 2 Diabetes and Diabetic Heart Disease","authors":"Jianglan Long, Yueyue Wang, Qiushi Fang, Zhe Shi, Zhenzhen Wang, Dan Yan","doi":"10.1002/rcm.70044","DOIUrl":"10.1002/rcm.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Over 70% of diabetic patients die from cardiovascular disease, in which diabetic heart disease (DHD) is an important cause of death in individuals with type 2 diabetes (T2D). It is hence imperative to explore the simple, rapid, and economical method for diagnosing DHD from T2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>T2D and DHD patients were recruited, and their serum samples were used for metabolomic analysis to identify differential metabolites. Logistic regression analysis and receiver operating characteristic curve analysis were performed to identify candidate biomarkers. Moreover, four machine learning methods were used to construct the integrated biomarker profiling (IBP) models with the candidate biomarkers. Gini impurity was employed to select characteristic candidate biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-four differential metabolites were identified in the serum of 58 T2D and 62 DHD patients. Logistic regression analysis indicated that 17 differential metabolites were protective factors, whereas 39 were risk factors for DHD. Further, 29 differential metabolites were identified as the candidate biomarkers of DHD after receiver operating characteristic curve analysis. After comparing the predictive performance of the four machine learning models, the IBP was constructed based on the eXtreme Gradient Boosting (XGBoost) with six candidate biomarkers, which were sphingomyelin (d18:0/16:1), deoxycholic acid, hexadecanedioic acid, phosphatidylcholine (20:5/18:3), L-tryptophan, and N-undecanoylglycine from the ranked results of Gini impurity. The accuracy of the IBP for distinguishing T2D and DHD reached 88.89%, with a 100% accuracy in predicting DHD from T2D patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The IBP, composed of six metabolites, can effectively predict DHD from T2D, and it is expected to become a screening indicator for early-stage DHD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083590","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}
Lingyu Ye, Shuding Sun, Ting Wang, Jia Song, Li Wang, Yufang Miao, Di Zhao, Qi Sun, Yan Wan, Suxiang Feng
Rationale
Depression is currently the third leading cause of disease burden worldwide by 2030. Jieyu Pills (JYP) comprise 10 herbs demonstrated clinical effectiveness in managing depression with low by-effects. Owing to the complexity of herbal compound formulations, identifying chemical constituents is insufficient to discover the specificity and correlation between quality and therapeutic efficacy. Thus, selecting and detecting appropriate quality control (QC) markers for herbal medicines remains a challenge.
Methods
This study has been screened and evaluated appropriate QC markers through a correlation analysis of “ingredient–pharmacological efficacy.” Firstly, chemical components of JYP were systematically characterized in vivo and in vitro using UHPLC-Orbitrap Fusion MS. Then, network pharmacology analysis was conducted to predict potential active components of JYP. Finally, core effectors of JYP were screened out as QC markers and subjected to targeted quantitative analysis.
Results
A total of 188 compounds were identified in vitro, and 47 prototype constituents plus 41 metabolites were detected in serum. Network analysis revealed 13 core targets such as AKT1 and TNF enriched in inflammation, apoptosis, and AGE-RAGE signaling pathways, aligning with known depression mechanisms. Integrating serum-exposed components with network results highlighted paeoniflorin, gallic acid, liquiritin, and their metabolites as central modulators of neuroinflammatory and neuroprotective processes. Based on this “chemical entity–metabolic fate–target–pathway” framework, 20 compounds were selected as potential QC markers, and quantitative analysis confirmed high batch consistency.
Conclusions
This study provides the first integrated in vitro–in vivo chemical and mechanistic profiling of JYP, elucidates its metabolic characteristics and core antidepressant pathways, and establishes scientifically grounded QC markers. The research provides a novel perspective for investigating complex herbal prescriptions.
{"title":"Comprehensive Characterization of the Chemical Constituents, Serum Pharmacochemistry, and Quality Control of Jieyu Pills Utilizing UHPLC-Orbitrap Fusion MS","authors":"Lingyu Ye, Shuding Sun, Ting Wang, Jia Song, Li Wang, Yufang Miao, Di Zhao, Qi Sun, Yan Wan, Suxiang Feng","doi":"10.1002/rcm.70042","DOIUrl":"10.1002/rcm.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Depression is currently the third leading cause of disease burden worldwide by 2030. Jieyu Pills (JYP) comprise 10 herbs demonstrated clinical effectiveness in managing depression with low by-effects. Owing to the complexity of herbal compound formulations, identifying chemical constituents is insufficient to discover the specificity and correlation between quality and therapeutic efficacy. Thus, selecting and detecting appropriate quality control (QC) markers for herbal medicines remains a challenge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study has been screened and evaluated appropriate QC markers through a correlation analysis of “ingredient–pharmacological efficacy.” Firstly, chemical components of JYP were systematically characterized in vivo and in vitro using UHPLC-Orbitrap Fusion MS. Then, network pharmacology analysis was conducted to predict potential active components of JYP. Finally, core effectors of JYP were screened out as QC markers and subjected to targeted quantitative analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 188 compounds were identified in vitro, and 47 prototype constituents plus 41 metabolites were detected in serum. Network analysis revealed 13 core targets such as AKT1 and TNF enriched in inflammation, apoptosis, and AGE-RAGE signaling pathways, aligning with known depression mechanisms. Integrating serum-exposed components with network results highlighted paeoniflorin, gallic acid, liquiritin, and their metabolites as central modulators of neuroinflammatory and neuroprotective processes. Based on this “chemical entity–metabolic fate–target–pathway” framework, 20 compounds were selected as potential QC markers, and quantitative analysis confirmed high batch consistency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provides the first integrated in vitro–in vivo chemical and mechanistic profiling of JYP, elucidates its metabolic characteristics and core antidepressant pathways, and establishes scientifically grounded QC markers. The research provides a novel perspective for investigating complex herbal prescriptions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083595","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}
Tom Higham, Katharina Luftensteiner, Laura van der Sluis, Maddalena Giannì, Maria Wiegele, Anastasia Papadogianni, Peter Steier, Daniela Gruber, Brigitte Schmidt, Katy Schmidt, Andrei Belinski, Romain Mensan, Maxim Kozlikin, Michael Shunkov, Petr Neruda, Zdeňka Nerudová, Barbara Horejs, John Schulze, Katerina Douka, Thomas W. Stafford Jr.
Rationale
Bone is commonly used in radiocarbon dating in archaeology and other disciplines. Despite advances in collagen extraction protocols, the process remains destructive, requiring sawing, drilling or crushing of bone material. While non-destructive approaches have recently been applied in ancient genomics and palaeoproteomics, no equivalent approach has been established for radiocarbon dating of bone. We explored whether this is possible using a series of experiments.
Methods
We experimented by using a water-based approach to extract soluble collagen from whole bone and teeth samples. We heated the samples in hot (75°C and 90°C) water for several hours. We obtained the soluble collagen fraction of the bone and purified and AMS dated the extracts. We used standard reference bones and samples from archaeological sites.
Results
We found that the amino acid composition, C/N atomic ratios, δ13C and δ15N values of the hot-water-extracted soluble collagen were comparable to collagen isolated from the same bones using classic Longin collagen methods. Bone and teeth from Bronze Age and Middle and Upper Paleolithic sites, which had been dated previously using routine destructive methods that involved acid demineralization, yielded dates on the water-soluble fraction that were in good agreement with these earlier results.
Conclusions
We show that a minimally destructive collagen extraction, coupled with an additional purification step such as ultrafiltration or XAD-2 purification, yields identical radiocarbon ages to those obtained via the routine destructive methods, but without any visible external damage. The method may allow us in future to date precious artefacts, ornaments and museum objects without significant alteration.
{"title":"Minimally Destructive Radiocarbon Dating of Bone","authors":"Tom Higham, Katharina Luftensteiner, Laura van der Sluis, Maddalena Giannì, Maria Wiegele, Anastasia Papadogianni, Peter Steier, Daniela Gruber, Brigitte Schmidt, Katy Schmidt, Andrei Belinski, Romain Mensan, Maxim Kozlikin, Michael Shunkov, Petr Neruda, Zdeňka Nerudová, Barbara Horejs, John Schulze, Katerina Douka, Thomas W. Stafford Jr.","doi":"10.1002/rcm.70040","DOIUrl":"10.1002/rcm.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Bone is commonly used in radiocarbon dating in archaeology and other disciplines. Despite advances in collagen extraction protocols, the process remains destructive, requiring sawing, drilling or crushing of bone material. While non-destructive approaches have recently been applied in ancient genomics and palaeoproteomics, no equivalent approach has been established for radiocarbon dating of bone. We explored whether this is possible using a series of experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We experimented by using a water-based approach to extract soluble collagen from whole bone and teeth samples. We heated the samples in hot (75°C and 90°C) water for several hours. We obtained the soluble collagen fraction of the bone and purified and AMS dated the extracts. We used standard reference bones and samples from archaeological sites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the amino acid composition, C/N atomic ratios, <i>δ</i><sup>13</sup>C and <i>δ</i><sup>15</sup>N values of the hot-water-extracted soluble collagen were comparable to collagen isolated from the same bones using classic Longin collagen methods. Bone and teeth from Bronze Age and Middle and Upper Paleolithic sites, which had been dated previously using routine destructive methods that involved acid demineralization, yielded dates on the water-soluble fraction that were in good agreement with these earlier results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We show that a minimally destructive collagen extraction, coupled with an additional purification step such as ultrafiltration or XAD-2 purification, yields identical radiocarbon ages to those obtained via the routine destructive methods, but without any visible external damage. The method may allow us in future to date precious artefacts, ornaments and museum objects without significant alteration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083606","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}
Clifton K. Fagerquist, Yanlin Shi, Mahesh Koirala, Maria T. Brandl
Rationale
Colicins are protein toxins produced by bacteria that destroy the nucleic acids or outer membranes of their bacterial neighbors. Their genes are encoded in small extra-chromosomal plasmids that play an important role in bacterial survival. Although colicins do not contribute to bacterial pathogen virulence, it is important to develop methods to identify molecular determinants that facilitate pathogen survival.
Methods
Shiga toxin-producing Escherichia coli (STEC) were analyzed for the presence of colicin-bearing plasmids using antibiotic induction, MALDI-TOF-TOF, Orbitrap mass spectrometry, and targeted top-down analysis using in-house software. Small plasmid sequencing was used to confirm plasmid-encoded genes as well as their upstream regulation. AlphaFold3 was used to rationalize expected (as well as anomalous) fragment ions detected by MS/MS post-source decay (PSD).
Results
Colicin immunity (Imm) proteins were detected and identified by targeted top-down mass spectrometry in two STEC strains (serotypes O26:H11 and O104:H7) that carried one or more colicin plasmids. ImBac, ImmD, and a 7.8 kDa hypothetical protein (whose gene resides on a plasmid that encodes a pore-forming colicin) were detected and identified. Whole genome sequencing (by other groups) and our small plasmid sequencing confirmed the colicin/immunity genes as well as their upstream regulatory control.
Conclusions
MALDI-TOF-TOF-MS/MS-PSD is an effective platform for rapid detection and identification of inducible antibacterial protein toxins. We also note that the previously reported glycine-enhanced aspartic acid effect (AAE) appears to occur most often at unstructured/linker regions of the polypeptide backbone.
{"title":"Colicin-Bearing Plasmids Carried by Shiga Toxin-Producing E. coli (STEC) Analyzed by Targeted Top-Down MS Analysis","authors":"Clifton K. Fagerquist, Yanlin Shi, Mahesh Koirala, Maria T. Brandl","doi":"10.1002/rcm.70031","DOIUrl":"10.1002/rcm.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Colicins are protein toxins produced by bacteria that destroy the nucleic acids or outer membranes of their bacterial neighbors. Their genes are encoded in small extra-chromosomal plasmids that play an important role in bacterial survival. Although colicins do not contribute to bacterial pathogen virulence, it is important to develop methods to identify molecular determinants that facilitate pathogen survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Shiga toxin-producing <i>Escherichia coli</i> (STEC) were analyzed for the presence of colicin-bearing plasmids using antibiotic induction, MALDI-TOF-TOF, Orbitrap mass spectrometry, and targeted top-down analysis using in-house software. Small plasmid sequencing was used to confirm plasmid-encoded genes as well as their upstream regulation. AlphaFold3 was used to rationalize expected (as well as anomalous) fragment ions detected by MS/MS post-source decay (PSD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Colicin immunity (Imm) proteins were detected and identified by targeted top-down mass spectrometry in two STEC strains (serotypes O26:H11 and O104:H7) that carried one or more colicin plasmids. ImBac, ImmD, and a 7.8 kDa hypothetical protein (whose gene resides on a plasmid that encodes a pore-forming colicin) were detected and identified. Whole genome sequencing (by other groups) and our small plasmid sequencing confirmed the colicin/immunity genes as well as their upstream regulatory control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MALDI-TOF-TOF-MS/MS-PSD is an effective platform for rapid detection and identification of inducible antibacterial protein toxins. We also note that the previously reported glycine-enhanced aspartic acid effect (AAE) appears to occur most often at unstructured/linker regions of the polypeptide backbone.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040111","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}
Andhika Yudha Prawira, Maharani Kartika Ramadhan, Tulus Maulana, Ni Luh Putu Rischa Phadmacanty, Rizki Fitrawan Yuneldi, Srihadi Agungpriyono, Berry Juliandi
Rationale
Sunda porcupine (Hystrix javanica) has quills that exhibit considerable morphological diversity and functionality, yet the molecular variation underlying these differences remains insufficiently explored. Comprehensive proteomic profiling provides an opportunity to examine peptide composition and keratin expression patterns across quill types. This study aims to characterize molecular distinctions among Sunda porcupine quills using label-free quantitative proteomic analysis.
Methods
Three quill types—spine, true quill, and rattle quill—were collected, cleaned, pulverized, and subjected to keratin-specific extraction employing reducing agents. Extracted proteins underwent in-solution digestion before analysis using LC–MS/MS on a high-resolution Orbitrap system. Peptide and protein identification utilized SequestHT against curated rodent keratin databases. Data were processed through multivariate statistical analyses, including PCA, PLS-DA, SOM, and heatmap clustering to assess quill-specific clustering, peptide distribution, and keratin profile variation among quill types.
Results
LC–MS/MS identified 653 peptides and 70 homologous proteins, revealing molecular variation among quill types. True quill and spine displayed overlapping peptide abundance patterns, whereas rattle quill demonstrated distinct clustering. Amino acid composition varied among quills, reflecting structural and functional differentiation. True quill and spine showed higher intensity of proteins than rattle quill. Keratin type I cuticular and cytoskeletal proteins were the most matched proteins. Protein profile indicated high similarity to keratins from Hystricomorpha rodent species.
Conclusion
The study demonstrates clear molecular differentiation among quill types, with true quill and spine exhibiting closer proteomic similarity than rattle quill. Distinct peptides identified in each quill category highlight their potential as biomarkers for quill-type discrimination, although further validation is required to confirm their diagnostic reliability.
{"title":"Label-Free Quantitative Proteomics Analysis Revealed the Peptide and Keratin Protein Pattern in Different Types of Sunda Porcupine (Hystrix javanica) Quill","authors":"Andhika Yudha Prawira, Maharani Kartika Ramadhan, Tulus Maulana, Ni Luh Putu Rischa Phadmacanty, Rizki Fitrawan Yuneldi, Srihadi Agungpriyono, Berry Juliandi","doi":"10.1002/rcm.70036","DOIUrl":"10.1002/rcm.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Sunda porcupine (<i>Hystrix javanica</i>) has quills that exhibit considerable morphological diversity and functionality, yet the molecular variation underlying these differences remains insufficiently explored. Comprehensive proteomic profiling provides an opportunity to examine peptide composition and keratin expression patterns across quill types. This study aims to characterize molecular distinctions among Sunda porcupine quills using label-free quantitative proteomic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three quill types—spine, true quill, and rattle quill—were collected, cleaned, pulverized, and subjected to keratin-specific extraction employing reducing agents. Extracted proteins underwent in-solution digestion before analysis using LC–MS/MS on a high-resolution Orbitrap system. Peptide and protein identification utilized SequestHT against curated rodent keratin databases. Data were processed through multivariate statistical analyses, including PCA, PLS-DA, SOM, and heatmap clustering to assess quill-specific clustering, peptide distribution, and keratin profile variation among quill types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LC–MS/MS identified 653 peptides and 70 homologous proteins, revealing molecular variation among quill types. True quill and spine displayed overlapping peptide abundance patterns, whereas rattle quill demonstrated distinct clustering. Amino acid composition varied among quills, reflecting structural and functional differentiation. True quill and spine showed higher intensity of proteins than rattle quill. Keratin type I cuticular and cytoskeletal proteins were the most matched proteins. Protein profile indicated high similarity to keratins from Hystricomorpha rodent species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study demonstrates clear molecular differentiation among quill types, with true quill and spine exhibiting closer proteomic similarity than rattle quill. Distinct peptides identified in each quill category highlight their potential as biomarkers for quill-type discrimination, although further validation is required to confirm their diagnostic reliability.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027982","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}
Wenbin Chen, Jiangbo Xi, Zhiyuan Gao, Juan Zhang, Junjun Zhang, Zhengwu Bai, Min Li
Rationale
Rapid structural elucidation of unknown pharmaceutical impurities is critical throughout the whole life cycle of drug development. It can be achieved by using multistage mass spectrometric analysis, in conjunction with the understanding of dissociation mechanisms of the ions generated by electrospray ionization.
Methods
Liquid chromatography-UV/photo diode array detection—high resolution multistage mass spectrometric analysis (HiRes MSn) was used to elucidate the structure of an impurity of silodosin. The structure was confirmed by 1D and 2D NMR spectroscopy.
Results
The impurity is identified as N-cyanomethylsilodosin, a solution degradant of silodosin. A novel 1,3-sigmatropic rearrangement was observed during one of its MS3 dissociation pathways. A mechanism is proposed for the 1,3-sigmatropic rearrangement, which is supported by the MSn behavior of a 13C-isotope labeled derivative of N-cyanomethylsilodosin.
Conclusion
Elucidation of such an intra-molecular rearrangement mechanism not only enriches our understanding of the gas phase dissociation chemistry, but also should facilitate future rapid structural characterization of unknown pharmaceutical impurities and metabolites using multistage mass spectrometric analysis.
{"title":"A Novel 1,3-Sigmatropic Rearrangement in an Iminium Ion Generated in Collision-Induced Decomposition During Electrospray Ionization High Resolution Multistage Mass Spectrometry","authors":"Wenbin Chen, Jiangbo Xi, Zhiyuan Gao, Juan Zhang, Junjun Zhang, Zhengwu Bai, Min Li","doi":"10.1002/rcm.70037","DOIUrl":"10.1002/rcm.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>Rapid structural elucidation of unknown pharmaceutical impurities is critical throughout the whole life cycle of drug development. It can be achieved by using multistage mass spectrometric analysis, in conjunction with the understanding of dissociation mechanisms of the ions generated by electrospray ionization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Liquid chromatography-UV/photo diode array detection—high resolution multistage mass spectrometric analysis (HiRes MS<sup>n</sup>) was used to elucidate the structure of an impurity of silodosin. The structure was confirmed by 1D and 2D NMR spectroscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The impurity is identified as <i>N</i>-cyanomethylsilodosin, a solution degradant of silodosin. A novel 1,3-sigmatropic rearrangement was observed during one of its MS<sup>3</sup> dissociation pathways. A mechanism is proposed for the 1,3-sigmatropic rearrangement, which is supported by the MS<sup>n</sup> behavior of a <sup>13</sup>C-isotope labeled derivative of <i>N</i>-cyanomethylsilodosin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Elucidation of such an intra-molecular rearrangement mechanism not only enriches our understanding of the gas phase dissociation chemistry, but also should facilitate future rapid structural characterization of unknown pharmaceutical impurities and metabolites using multistage mass spectrometric analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"40 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016769","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}
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