Journal of Chromatography B最新文献

{"title":"Rapid quantification of polymyxin B in human pulmonary epithelial lining fluid by LC-MS/MS and its clinical application","authors":"Yu Wang ,&nbsp;Xiaofen Liu ,&nbsp;Yan Chen ,&nbsp;Beining Guo ,&nbsp;Jiao Liu ,&nbsp;Jing Zhang","doi":"10.1016/j.jchromb.2024.124332","DOIUrl":"10.1016/j.jchromb.2024.124332","url":null,"abstract":"<div><div>Pulmonary epithelial lining fluid (ELF) was commonly used for the pharmacokinetic study in lower respiratory tract infections. To characterize the intrapulmonary pharmacokinetic properties of polymyxin B following aerosol delivery, we developed and fully validated a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantifying polymyxin B in human bronchoalveolar lavage fluid (BALF). The ELF concentrations were calculated by the BALF values of polymyxin B using urea as a volume normalizer. Chromatographic separation was achieved on a Phonomenex Kinetex XB-C18 column(100 mm × 2.1 mm I.D., 2.6 μm)in acetonitrile and water both containing 0.2 % formic acid. The flow rate was set as 0.4 mL/min for a 3.5 min running time. Protein precipitation was used in preparing BALF samples with polymyxin E1 as an internal standard. Polymyxin B was detected under multiple reaction monitoring conditions using the electrospray ionization interface running in the positive ionization mode. The assay showed a good linear relationship over the tested concentration ranges of 0.0300/0.00306–––10.0/1.02 mg/L for polymyxin B1/B2 in bronchoalveolar lavage fluid (R² &gt; 0.99). The inter- and inter-day precisions (RSD, %) were &lt; 12.2 %(15.2 % for LLOQ samples)and the accuracies (%) were within the range of 94.3 ∼ 110.4 %. This reliable LC–MS/MS method for detection of polymyxin B was successfully applied to conduct a pulmonary penetration study in patients following aerosol administration.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124332"},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446262","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":"Characterization of etomidate and emerging analogs in human hair using UHPLC-MS/MS and confirmation in real forensic cases","authors":"Lina Pei ,&nbsp;Shuo Yang ,&nbsp;Chaodan Cui ,&nbsp;Xin Wang ,&nbsp;Ping Xiang ,&nbsp;Yonghui Dang ,&nbsp;Yan Shi","doi":"10.1016/j.jchromb.2024.124340","DOIUrl":"10.1016/j.jchromb.2024.124340","url":null,"abstract":"<div><div>The regulation of etomidate, a widely used drug for anesthesia induction and short surgical procedures, has led to the emergence of etomidate analogs such as metomidate, propoxate, and isopropoxate. This study introduces and validates a simple, rapid, and cost-effective ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination and quantification of etomidate, etomidate acid, metomidate, propoxate, and isopropoxate in human hair. Using a five-minute gradient elution on a Phenomenex Kinetex Biphenyl column, the method achieves low limits of quantification (LOQs), ranging from 5 to 20 pg/mg. Method validation confirms robust linear calibration curves for the target substances in hair samples within the range of LOQs to 1000 pg/mg, with average correlation coefficients (r) all exceeding 0.999. The method also achieves acceptable intra-day and inter-day precision (&lt;15 %) and trueness(bias, −10.9 % to 14.4 %). The matrix effect ranges from 46.9 % to 94.2 %, and the extraction recovery rate ranges from 84.5 % to 105 %. When applied to authentic cases, this method successfully identified 56 positive samples. The concentrations of etomidate, etomidate acid, metomidate, propoxate, and isopropoxate in positive samples ranged from 27 to 1.5 × 10⁵ pg/mg, 21 to 1.5 × 10³ pg/mg, 18 to 8.7 × 10⁴ pg/mg, 25 to 1.6 × 10⁴ pg/mg, and 22 to 5.0 × 10⁵ pg/mg, respectively.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124340"},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492170","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":"Fe3O4@MXene@PEI aerogel immobilized acetylcholinesterase for inhibitor screening from herbal plants","authors":"Di Zhao ,&nbsp;Zhonghua Li ,&nbsp;Xiaobing Liu ,&nbsp;Zhiyu Zhang ,&nbsp;Huifen Ma ,&nbsp;Pan Wang ,&nbsp;Zhenqiang Zhang ,&nbsp;Junying Song ,&nbsp;Kai Hu","doi":"10.1016/j.jchromb.2024.124345","DOIUrl":"10.1016/j.jchromb.2024.124345","url":null,"abstract":"<div><div>Screening of acetylcholinesterase (AChE) inhibitors is a common strategy in drug discovery for treating Alzheimer’s disease. Herein, AChE was immobilized onto magnetic polyethyleneimine-based MXene aerogels through both electrostatic interactions and covalent bonds, enabling its application in AChE activity assays and inhibitor screening of herbal plants. The composite was analyzed using a range of techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and Zeta potential analysis, to gain insight into its chemical and physical properties. The proposed Fe₃O₄@MXene@PEI<strong>-</strong>AChE composite exhibited enhanced temperature and pH stability, as evaluated by Ellman’s method, along with good reusability. The Michaelis Menten constant (<em>K</em>_m) of the immobilized AChE was calculated to be 0.68 mmol/L. Additionally, an inhibition kinetic study was conducted to verify the feasibility of utilizing the immobilized enzyme to screen for inhibitors, with huperzine A employed as a model inhibitor. The proposed strategy was employed to compare the AChE inhibitory activity of 18 commonly used herbal medicines for treating AD, revealing both the aqueous and alcoholic extracts of Coptis chinensis as exhibiting the highest AChE inhibitory activity. Finally, the screening of AChE inhibitors in Coptis chinensis extracts were conducted by combining the proposed strategy with UPLC-Q-Orbitrap high resolution mass spectrometry. This study presents a feasible strategy for monitoring AChE activity and holds considerable potential for further exploration of AChE-inhibiting active ingredients in herbal medicines.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124345"},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531351","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":"Quantitative determination by UHPLC-MS/MS of 18 common drugs of abuse and metabolites, including THC and OH-THC, in volumetric dried blood spots: a sustainable method with minimally invasive sampling","authors":"Christina Ververi ,&nbsp;Claudia Gentile ,&nbsp;Marta Massano ,&nbsp;Alberto Salomone ,&nbsp;Marco Vincenti","doi":"10.1016/j.jchromb.2024.124337","DOIUrl":"10.1016/j.jchromb.2024.124337","url":null,"abstract":"<div><div>The increased use of drugs of abuse urges forensic toxicologists to create quick, simple, minimally invasive sampling techniques for biological fluids combined with analytical methods assuring accurate results. To this purpose, a method was developed aimed at quantifying 18 drugs of abuse and metabolites in DBS. Validation of the method was conducted by spiking blank whole blood with the analytes on <em>Capitainer® B</em> cards. The extracts were analyzed by a targeted UHPLC-MS/MS method. Linear calibration was achieved in the range of 1–100 ng/mL for: amphetamine, MDA, MDMA, methamphetamine, cocaine, codeine, benzoylecgonine, cocaethylene, morphine, 6-MAM, buprenorphine, methadone, EDDP, ketamine, norbuprenorphine norketamine, THC, and OH-THC. Experimental LOD was found at 0.5 ng/mL for all analytes except for norbuprenorphine, THC and THC-OH which yielded a LOD of 1 ng/mL. Intra- and inter-day accuracy was satisfactory with bias% resulting within 5%. Evaluation of intra- and inter-day precision yielded CV% values within 20%, for all compounds except EDDP. Average extraction recovery calculated at low (2 ng/mL) and high (75 ng/mL) concentration levels was 63% while average matrix effect determined at the same levels was found to be within 85% − 115% for all analytes except from codeine (70%) and MDMA (131%). The method was applied to authentic blood samples spotted onto the DBS card and the minimum value detected was 1.3 ng/mL. HPLC-MS/MS proved capable to identify all the targeted analytes at low concentrations in the small blood volumes obtainable from DBS cards, which in turn confirmed to be effective and sustainable micro-sampling devices.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124337"},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated metabolomics and network pharmacology reveal the procoagulant mechanisms of Cirsium setosum extracts","authors":"Xiao Yang ,&nbsp;Yingjin Wang ,&nbsp;Shuangyi Gong ,&nbsp;Tingjian Xiong ,&nbsp;Lihang Xie","doi":"10.1016/j.jchromb.2024.124335","DOIUrl":"10.1016/j.jchromb.2024.124335","url":null,"abstract":"<div><div>As a medicinal plant, <em>Cirsium setosum</em> has excellent procoagulant effects and has long been used as a cure for hemoptysis, epistaxis, uremia and metrorrhagia caused by blood heat. However, the key medicinal part of <em>C. setosum</em>, as well as the biologically active substances that play a major role, are not known. In this study, the aboveground, underground and whole grass portions of <em>C. setosum</em> were subjected to a coagulation comparison experiment to determine the primary active procoagulant compounds. The main active procoagulant compounds of <em>C. setosum</em> were then screened using a comparative metabolomics analysis between aboveground and underground. Network pharmacology analysis was used to construct the “active ingredient-disease target-pathway” network. Finally, molecular docking was used to verify the binding ability and affinity between the key active ingredients obtained from the screening and the targets. The results indicated that the aboveground part of <em>C. setosum</em> could significantly shorten activated partial thromboplastin time (APTT) and that this part exerts substantial procoagulant effects. The total phenol, total flavonoid and total alkaloid content of the aboveground part was measured to be higher than those of the underground part and whole grass. Furthermore, comparative metabolomics analysis as well as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database and literature search screening yielded 10 active substances, including naringenin, guanine, 2,4-di-<em>tert</em>-butylphenol, calycosin-7-O-beta-D-glucoside, flavone, vitexin, and tiliroside, which may be related to the coagulation-promoting properties of <em>C. setosum</em> and its therapeutic effects on coagulation-related disorders. Network pharmacological analysis revealed that <em>C. setosum</em> may exert procoagulant effects mainly through tiliroside, calycosin-7-O-beta-D-glucoside, and flavone, which act on key target proteins, such as SRC, PRKACA, EGFR, AKT1, MAPK3, and GSK3B. In summary, <em>C. setosum</em> exerts its procoagulant and therapeutic effects on coagulation-related diseases through multiple compounds, targets, and pathways.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124335"},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418162","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":"Generation of affinity maps for thiazolidinediones with human serum albumin using affinity microcolumns. II. Effects of advanced glycation end products on multisite drug binding","authors":"Sadia Sharmeen,&nbsp;Ashley G. Woolfork,&nbsp;David S. Hage","doi":"10.1016/j.jchromb.2024.124333","DOIUrl":"10.1016/j.jchromb.2024.124333","url":null,"abstract":"<div><div>Multisite protein interactions by the thiazolidinedione-class drugs pioglitazone and rosiglitazone were examined by using high-performance affinity microcolumns that contained normal human serum albumin (HSA) vs HSA that had been modified to form advanced glycation end products by glyoxal (Go) or methylglyoxal (MGo). The results were used to generate an affinity map for these drugs at several key regions on HSA. Strong binding (∼10⁵ M⁻¹) by these drugs was seen at both Sudlow sites I and II. About a 50 % decrease in the affinities at Sudlow site II was observed for pioglitazone for Go-modified HSA, while either a 47 % decrease or 1.6-fold increase in affinity was seen for MGo-modified HSA, depending on the extent of modification. The binding affinity for rosiglitazone at Sudlow site II had a 40–83 % decrease for Go-modified HSA and either a non-significant change or 1.4-fold increase for MGo-modified HSA. At Sudlow site I, pioglitazone gave a 41 % decrease in affinity for either Go or MGo-modified HSA, and for rosiglitazone up to a 55 % decrease or 1.3-fold increase in affinity was noted. Positive allosteric effects were seen by these drugs with the tamoxifen site of HSA, and neither drug had any notable binding at the digitoxin site for the normal or modified forms of HSA. Rosiglitazone also had weak interactions at a site in subdomain IB, which increased in affinity by up to 5.0-fold with the Go- or MGo-modified HSA. This study illustrated how affinity microcolumns can be used to provide a detailed analysis of solute-protein systems that involve complex interactions. The data obtained should also be valuable in providing a better understanding of how drug interactions with HSA and other proteins can be altered by modifications of these binding agents in diseases such as diabetes.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124333"},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418163","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":"Serum metabolome alterations in hyperhomocysteinemia based on targeted and non-targeted MS-platforms","authors":"Xinshu Zhao ,&nbsp;Xiaowei Liu ,&nbsp;Liyan Liu ,&nbsp;Rui Chen","doi":"10.1016/j.jchromb.2024.124336","DOIUrl":"10.1016/j.jchromb.2024.124336","url":null,"abstract":"<div><h3>Background and aims</h3><div>Hyperhomocysteinemia (Hhcy) is a pathological condition marked by increased level of homocysteine and serves as an independent risk factor for a range of diseases including cardiovascular diseases and Alzheimer’s disease. This study aims to examine alterations in Hhcy-related metabolites using serum metabolomics and unravel the distinct metabolic pathways involved, thereby offering a theoretical foundation for the early prevention and treatment of Hhcy.</div></div><div><h3>Methods</h3><div>Serum samples were collected from 56 individuals with Hhcy and 44 healthy controls. Metabolic alterations in Hhcy were assessed through multi-platform serum metabolomics analyses. Through multivariate statistical analysis and regression modeling, distinct metabolites in the serum were identified, and various metabolic pathways associated with Hhcy were investigated.</div></div><div><h3>Results</h3><div>Our findings revealed 21 significant different metabolites that distinguished Hhcy from healthy controls. These varied metabolites primarily comprised 10 organic acids, 4 amino acids, 2 fatty acids, and 5 other metabolites. The key differential metabolic pathways identified were the TCA cycle, pyruvate metabolism, arginine biosynthesis, as well as alanine, aspartate, and glutamate metabolism.</div></div><div><h3>Conclusions</h3><div>This study elucidated the variances in metabolic profiles between Hhcy and healthy control groups, highlighting distinct metabolic pathways that may help explain the etiology of Hhcy. These findings offer valuable insights to address the knowledge gaps related to the metabolic alterations associated with Hhcy.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124336"},"PeriodicalIF":2.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386953","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":"Efficient purification of soluble receptor for advanced glycation end-products from Sus scrofa lung tissue and synthesis of its binding ligand, glycated bovine serum albumin","authors":"Tamás Madarász,&nbsp;Miklós Nyitrai,&nbsp;Edina Szabó-Meleg","doi":"10.1016/j.jchromb.2024.124326","DOIUrl":"10.1016/j.jchromb.2024.124326","url":null,"abstract":"<div><div>A receptor for advanced glycation end products (RAGE) has emerged as a crucial player in various pathological conditions due to its involvement in inflammation and cellular dysfunction. Its soluble isoform, sRAGE, has garnered significant attention for its competitive inhibitory effects and potential therapeutic applications. However, obtaining sRAGE with appropriate glycosylation patterns for binding to glycated proteins has been challenging, often requiring costly expression systems. Here, we present a novel approach for producing and purifying sRAGE from Sus scrofa lungs, bypassing the need for expensive expression systems. Previous protocols for sRAGE extraction faced reproducibility issues due to high viscosity and haemoglobin content of the solution. To address this, we developed a method for selective haemoglobin precipitation using a zinc-containing buffer, enabling purification via various chromatographic methods. Through a combination of chromatographic techniques, we obtained sRAGE in suitable purity, identified using HPLC-MS/MS. Additionally, producing glycated proteins for RAGE receptor activation often involved lengthy protocols or inadequate separation from reactants. Thus, we devised a rapid method for producing and purifying pure BSA glycated with ribose, addressing a critical gap in the field. Functional studies, conducted using Native PAGE, demonstrated the capability of purified proteins to bind to each other.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124326"},"PeriodicalIF":2.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of UPLC-MS/MS-based metabolomics and desorption electrospray ionization-mass spectrometry imaging reveals that Shouhui Tongbian Capsule alleviates slow transit constipation by regulating bile acid metabolism","authors":"Na Zhang ,&nbsp;Dong Guo ,&nbsp;Na Guo ,&nbsp;Dawei Yang ,&nbsp;Han Yan ,&nbsp;Jingchun Yao ,&nbsp;He Xiao ,&nbsp;Mingguo Shao ,&nbsp;Yongxia Guan ,&nbsp;Guimin Zhang","doi":"10.1016/j.jchromb.2024.124331","DOIUrl":"10.1016/j.jchromb.2024.124331","url":null,"abstract":"<div><div>Slow transit constipation (STC) is a common intestinal disorder. Some studies reported that Shouhui Tongbian Capsule (SHTB) can effectively mitigate STC symptoms. A detailed understanding of the changes in the endogenous metabolite profile of rats is crucial for a more accurate comprehension of the molecular pathological characteristics of SHTB in treating STC. In the present study, a method integrating metabolomics based on Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI) was proposed to investigate serum, feces and colon tissue metabolic alterations of STC rats induced by diphenoxylate and the effect of SHTB treatment on metabolism. Then, Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis for verifying the potential mechanism of SHTB in treating STC. As a result, we first indicated that SHTB significantly improved intestinal peristalsis and low fecal water content in STC rats. Furthermore, after treatment with SHTB, the thickness of muscle layers was increased, demonstrated SHTB’s effectiveness in reducing intestinal injury in STC rats. Besides, bile acid (BA) metabolomics based on UPLC-MS/MS revealed significant increase in serum levels of Cholic acid (CA), Deoxycholic acid (DCA), Chenodeoxycholic acid (CDCA), Ursodeoxycholic acid (UDCA), and Glycolithocholic acid (GLCA), whereas the contents of CA and DCA in feces were significantly decreased in STC rats. Nonetheless, they returned to the control levels after the SHTB administration. ELISA results showed that SHTB significantly hindered the excessive reabsorption of BAs by inhibiting apical sodium-dependent bile acid transporter (ASBT), organic solute transporter alpha (OSTα) and organic solute transporter beta (OSTβ) in the ileum tissue of STC rats. Furthermore, the DESI-MSI analysis revealed that SHTB remarkably enhanced DCA in the colon tissue of STC rats. The WB results indicated that SHTB reinstated Takeda G-protein–coupled receptor 5 (TGR5) expression, a receptor for BAs and a key regulator of colonic motility. Consequently, DCA exerted its effects on TGR5, leading to the promotion of colonic motility. This study provided more comprehensive and detailed information about the BA metabolomics in the serum, feces and colon of STC rats. These findings highlighted the promising potential of metabolomics based on UPLC-MS/MS and DESI-MSI method for application in the study of STC diseases.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124331"},"PeriodicalIF":2.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379723","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 of an LC-HRMS non-targeted method for comprehensive profiling of the exposome of nicotine and tobacco product users – A showcase for cigarette smokers","authors":"Alpeshkumar Kachhadia,&nbsp;Therese Burkhardt,&nbsp;Gerhard Scherer,&nbsp;Max Scherer,&nbsp;Nikola Pluym","doi":"10.1016/j.jchromb.2024.124330","DOIUrl":"10.1016/j.jchromb.2024.124330","url":null,"abstract":"<div><div>The global prevalence of electronic cigarettes, heated tobacco products, and other smokeless alternatives has grown significantly in the last ten years. These products have been suggested as combustion-free alternatives for conventional tobacco products like cigarettes, aiming to reduce the negative health impacts associated with smoking. However, the impact of those products on the health and safety of the general population are still unclear, as the absolute exposure from those products has not been thoroughly studied, yet. In this project, a non-targeted LC-HRMS method was developed comprising four different analytical modes for the investigation of the exposure profile in urine of the product users. The method is characterized by its high sensitivity and reproducibility, as shown during method validation. As a proof of concept, we first applied this method to detect significant differences in biomarkers of exposure (BoEs) between smokers and non-smokers. We observed a total of 171 BoEs significantly elevated in smokers, including several well-known biomarkers of smoke exposure like nicotine and its metabolites, mercapturic acid derivatives, and phenolic compounds. Some of the detected biomarkers are present at low ng/mL concentrations in urine, proving the high sensitivity needed for a holistic exploration of the exposome. Moreover, we were able to identify BoEs that have not been reported previously for smoking, such as 2,6-dimethoxyphenol and 7-methyl-1-naphthol glucuronide.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124330"},"PeriodicalIF":2.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374847","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}