Journal of Chromatography B最新文献

{"title":"Limitations in LC-MS/MS application for adagrasib and pembrolizumab quantification in rat plasma","authors":"Zvonimir Mlinarić","doi":"10.1016/j.jchromb.2024.124354","DOIUrl":"10.1016/j.jchromb.2024.124354","url":null,"abstract":"<div><div>An article by Harsha Shi et al. raises multiple concerns regarding sample preparation, the presence of the analyte in the analyzed solution, authenticity of the MS spectra, administration of drugs and blood collection, choice of internal standard, obtained pharmacokinetic parameters and usage of chromatographic column and solvents. While the research topic is interesting and the development of bioanalytical methods for novel drugs is crucial, this article does not seem to meet the analytical and methodological standards for the reliable determination of adagrasib and pembrolizumab in plasma samples. A detailed explanation is given in the letter.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124354"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611288","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":"LC-MS/MS method for quantitative profiling of ketone bodies, α-keto acids, lactate, pyruvate and their stable isotopically labelled tracers in human plasma: An analytical panel for clinical metabolic kinetics and interactions","authors":"Minoo Afshar ,&nbsp;Gerrit van Hall","doi":"10.1016/j.jchromb.2023.123906","DOIUrl":"10.1016/j.jchromb.2023.123906","url":null,"abstract":"<div><p>An important area within clinical research is <em>in vivo</em> metabolism of ketone bodies (β-hydroxybutyrate and acetoacetate) and in connection metabolites that may affect their production and/or cellular transport such as the keto-acids from the branched-chain amino acids, lactate and pyruvate. To determine <em>in vivo</em> metabolite turnover, availability of accurate and sensitive methods for analyzing the plasma concentrations of these metabolites and their stable isotopically labeled enrichments is mandatory. Therefore, the present study describes a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous analysis of ketone bodies, α-keto acids, lactate, pyruvate, and their tracer enrichments in humans using 2 different derivatization techniques with 4-bromo-N-methylbenzylamine and O-benzylhydroxylamine as derivatization reagents, and 1-ethyl-3-dimethylaminopropyl carbodiimide as coupling compound followed by a single LC-MS/MS run. The method was validated for matrix effects, linearity, accuracy, precision, recovery, stability, and enrichment (ratio) analysis of a stable isotopically labelled analytes (tracers) continuously infused in humans divided by the unlabeled endogenous analyte (tracee) that makes it possible to quantify the analyte <em>in vivo</em> synthesis and degradation rates. The applied parallel derivatization procedure yielded good sensitivity for all analytes of interest and their tracers. Despite the double derivatization method, mixing the ethyl acetate portions at the final stage made it possible to simultaneously analyze all compounds in a single LC-MS/MS run. Moreover, the liquid chromatography method was optimized to robustly quantify the keto acids derived from leucine (α-keto-isocaproic acid) and isoleucine (α-keto-β-methylvaleric acid), the compounds with similar chemical structure and identical molecular weights. The presented method is designed and validated for human plasma. However, care should be taken in blood sampling and processing procedures as well as quick freezing and storage at −80 °C due to the instability of especially acetoacetate.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1230 ","pages":"Article 123906"},"PeriodicalIF":3.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570023223003161/pdfft?md5=d7c89723ab36f45ae3a8e526927b67c0&pid=1-s2.0-S1570023223003161-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476386","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":"4D DIA-PRM proteomic study identifying modulated pathways and biomarkers associated with pelvic organ prolapse","authors":"Wei Deng ,&nbsp;Zhifeng Zhong ,&nbsp;Yuehong Tong ,&nbsp;Jun Liu ,&nbsp;Xiaofen Wang ,&nbsp;Lili Xu ,&nbsp;Yufeng Li ,&nbsp;Xiaodan Chen ,&nbsp;Qingfeng Wei ,&nbsp;Jun Rao","doi":"10.1016/j.jchromb.2023.123916","DOIUrl":"10.1016/j.jchromb.2023.123916","url":null,"abstract":"<div><p>Pelvic organ prolapse (POP) is a highly disabling condition that negatively affects the quality of life of millions of women worldwide. However, the underlying mechanisms associated with the development and progression of the disease remain poorly understood. Here, an untargeted four-dimensional data-independent acquisition (4D DIA)-based proteomics approach was applied to vaginal wall tissue samples from POP (n = 19) and control (n = 8) patients to identify potential diagnostic biomarker(s) for POP and examine the molecular mechanisms underlying the disease. Of the 5713 tissue proteins that were detected, 1957 proteins were significantly changed in POP patients. Further bioinformatics analysis revealed that multiple biological processes including protein digestion &amp; absorption, retrograde endocannabinoid signaling, tyrosine metabolism, and nucleotide metabolism were significantly enriched and associated with the pathogenesis of POP. Interestingly, 16 of these differentially expressed proteins associated with four pathways were also identified by targeted parallel reaction monitoring (PRM) proteomics analysis on the same 27 tissue samples. Changes in 94 % (15/16) of these proteins were consistent with the 4D DIA data. Furthermore, most proteins displayed good diagnostic accuracy with high area under the curve (AUC) values (AUC＞0.8). Specifically, five proteins including ELN, COL6A2, ENTPD1, AOC3, and COX7A2 distinguished between POP and control patients with very high accuracy (AUC ≥ 0.95) in both 4D DIA and PRM analyses, and may therefore be potential diagnostic biomarkers for POP. In summary, the present study not only provided several potential biomarker(s) for effective POP diagnosis, but extended our knowledge of the key regulatory pathways associated with the disease.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1230 ","pages":"Article 123916"},"PeriodicalIF":3.0,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476384","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":"Chlordecone determination in serum by LC-MS/MS and the importance of low limit of detection","authors":"Souleiman El Balkhi ,&nbsp;Franck Saint-Marcoux","doi":"10.1016/j.jchromb.2023.123915","DOIUrl":"10.1016/j.jchromb.2023.123915","url":null,"abstract":"<div><p>Chlordecone is an organochlorine insecticide that has been used intensively from 1973 to 1993 in the French West Indies banana fields to control root borers. This use has resulted in persistent pollution of soils and waters, and people have been and are still exposed mainly through food. Epidemiological studies showed that this exposure is associated with health disorders, including prostate cancer, prematurity, cognitive or motor development. The measurement of chlordecone in serum is considered as the best surrogate, though no clear and definitive cut-off value has been established. This renders necessary the development of analytical methods with the lowest limit of detection as possible. While most published methods have utilized GC–MS or GC–MS/MS, in the present study we report an LC-MS/MS method based on a simple QuEChERS salts extraction. The whole procedure was validated according to ISO 15189 requirements and reached LOD and LOQ values of 0.007 and 0.02 µg/L, respectively. It was applied to more 10 000 serum samples of French Indies inhabitants. More than a half had a concentration below 0.1 µg/L and more than one third of them exhibiting a concentration below 0.05 µg/L. The capability of this LC-MS/MS method to detect very low concentrations highlights its utility in exploring the health impact of chlordecone.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1230 ","pages":"Article 123915"},"PeriodicalIF":3.0,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method for quantifying lenacapavir plasma concentrations: Application to therapeutic monitoring","authors":"Raymond E. West III ,&nbsp;Patrick J. Oberly ,&nbsp;Sharon A. Riddler ,&nbsp;Thomas D. Nolin ,&nbsp;Aaron S. Devanathan","doi":"10.1016/j.jchromb.2023.123905","DOIUrl":"10.1016/j.jchromb.2023.123905","url":null,"abstract":"<div><p>Although current antiretroviral therapy (ART) effectively suppresses HIV in the blood, regimens may fail due to suboptimal treatment history and non-adherence to ART. In these scenarios, accumulation of viral resistance mutations to ART drug classes may occur. For these treatment-experienced people living with HIV (PLWH), activity against resistant viral strains is required; lack of therapeutic efficacy will result in continued viral replication and progression to acquired immunodeficiency syndrome. New treatment options have emerged. Lenacapavir is a first-in-class long-acting HIV-1 capsid inhibitor approved for the treatment of HIV in treatment-experienced patients. Lenacapavir is approved with an initiation regimen of oral and subcutaneous injection dosing followed by subcutaneous self-injection every 6 months. With infrequent dosing, therapeutic drug monitoring may be necessary to ensure adequate concentrations are consistently achieved in the plasma to assure treatment adherence and prevent further HIV resistance formation. To this end, we developed and validated a highly selective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify lenacapavir concentrations in human plasma. A simple protein precipitation with acetonitrile followed by supernatant dilution was performed. Lenacapavir and its stable labeled internal standard were separated at 1.90 min using a multi-step UPLC gradient. The assay for lenacapavir quantification was extensively validated according to the United States Food and Drug Administration Bioanalytical Guidelines over a clinically relevant range of 0.1 to 500 ng/mL with excellent linearity (R² ≥ 0.9960). This analytical method achieves acceptable performance of trueness (89.7–104.1 %), repeatability, and precision (CV &lt; 15 %). We applied this method to quantify a clinical sample and to determine the percent protein-unbound. This method can be utilized for the therapeutic monitoring of lenacapavir in human plasma for monitoring HIV treatment efficacy.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1230 ","pages":"Article 123905"},"PeriodicalIF":3.0,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688075","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":"Rapid ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three characteristic urinary saccharide metabolites in patients with glycogen storage diseases (type Ⅰb and Ⅱ)","authors":"Jianwei Ren ,&nbsp;Yufang Ma ,&nbsp;Mingsheng Ma ,&nbsp;Juan Ding ,&nbsp;Jingjing Jiang ,&nbsp;Xin Zheng ,&nbsp;Xiaohong Han","doi":"10.1016/j.jchromb.2023.123900","DOIUrl":"10.1016/j.jchromb.2023.123900","url":null,"abstract":"<div><p>Urinary 1,5-anhydroglucitol (1, 5-AG), 6-α-D-glucopyranosyl-maltotriose (Glc₄) and maltotetraose (M₄) are important biomarkers for glycogen storage disease (types Ib and Ⅱ). This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect these three urinary saccharide metabolites. Urine samples were diluted and then analyzed. Chromatographic separation was performed on an Acquity™ UPLC Amide column (2.1 × 100 mm, 1.7 μm) with gradient elution. The quantitation of analytes was achieved on a 5500 Qtrap mass spectrometer using negative multiple reaction monitoring (MRM) mode. The calibration curves for all analytes were linear over the range of 0.500 to 100 μg/mL with a correlation coefficient, <em>R²</em> ≥ 0.999. The percent relative standard deviations (RSD%) were ≤12.8%, and the percent relative errors (RE%) were in the range of −11.7%–11.0%. The relative matrix effects of all analytes were between 87.2% and 104% with RSD% &lt; 3.10% across three concentrations. The developed analytical method was simple, accurate, and reliable for rapid and simultaneous analysis of these three urinary saccharide metabolites. It was applied to healthy volunteers and patients. To our knowledge, it was the first validated assay for urinary maltotetraose quantification. This work provides support for exploring the potential of maltotetraose as a biomarker for Pompe disease.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1229 ","pages":"Article 123900"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41098082","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":"Analytical studies on some pesticides with antifungal effects: Simultaneous determination by HPLC, investigation of interactions with DNA and DNA damages","authors":"Boğaç Buğra Barut ,&nbsp;Cem Erkmen ,&nbsp;Seda İpek ,&nbsp;Sercan Yıldırım ,&nbsp;Aylin Üstündağ ,&nbsp;Bengi Uslu","doi":"10.1016/j.jchromb.2023.123862","DOIUrl":"10.1016/j.jchromb.2023.123862","url":null,"abstract":"<div><p>A simple, and fast method was developed for the simultaneous determination of five fungicides, namely thiram (THR), epoxiconazole (EPO), hexaconazole (HEX), tebuconazole (TEB), and diethofencarb (DIE), in different matrices by HPLC-UV. Parameters influencing the peak shape and resolution, such as the composition of mobile phase, pH and concentration of buffer solution, and column temperature, were examined and optimized. The proposed method was validated in terms of linearity, sensitivity, precision, and accuracy. Forced degradation studies were carried out for all analytes to demonstrate the specificity of the method and to evaluate the stability of analytes under different conditions. DNA interaction and DNA damage studies were conducted by HPLC and comet assay, respectively. All fungicides were found to bind DNA, except for DIE. While the binding coefficients for EPO, HEX, and TEB were of the order of 10⁴, THR was found to interact more strongly with DNA with a binding coefficient of higher than 10⁶. DIE did not induce DNA damage at any concentration tested. On the other hand, TEB, HEX, and EPO induced DNA damage up to 30 µg/mL. THR showed cytotoxic effects at 20 and 30 µg/mL and caused significant DNA damage at lower concentrations.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1229 ","pages":"Article 123862"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214948","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":"An alginate-based eutectogel impregnated with polyvinylpyrrolidone/benzoic acid deep eutectic solvent and magnetic carboxylated multiwalled carbon nanotubes: Evaluated as sorbent in green microextraction of pesticides","authors":"Zeinab Asghari ,&nbsp;Hassan Sereshti ,&nbsp;Sara Soltani ,&nbsp;Massoud Taghizadeh ,&nbsp;Sajad Karami ,&nbsp;Mehdi Esmaeili Bidhendi ,&nbsp;Shahabaldin Rezania","doi":"10.1016/j.jchromb.2023.123865","DOIUrl":"10.1016/j.jchromb.2023.123865","url":null,"abstract":"<div><p>This article presents the synthesis and application of a novel magnetic eutectogel constituting a polymeric deep eutectic solvent (PDES), carboxylated multiwall carbon nanotube (MWCNT-COOH), and super-dispersible/super-paramagnetic polyvinylpyrrolidone coated-Fe₃O₄ nanocrystals incorporated in alginate gel. Different methods were used for the characterization of novel polymeric based DES gel including FT-NMR, ATR-FTIR, and SEM were used. The novel DES eutectogel was used for the extraction of pesticides from honey. The modified eutectogel with PDES, MWCNT, and PDES-MWCNT showed 1.8-, 1.4-, and 2.5-fold enhancement in the sorption efficiency under green magnetic micro-solid-phase extraction (MSPE) method before GC–MS analysis. Important factors including the acidity of the samples, adsorption and desorption conditions, and the ionic strength of the preparation solution were investigated. The matrix effect, specificity, the quantification limits (0.023–1.023 μg kg⁻¹), linear dynamic range (0.023–500 µg kg⁻¹ with <em>R²</em> of 0.9845–0.9986), relative standard deviations (&lt;8.4%), were evaluated. In addition, the method was used to analyze 12 pesticides in four samples of honey. In the spiked concentration range of 0.1 to 10 μg kg^-, the obtained recoveries were between 73.2 and 110.8% (RSD% = 8.1%, n = 3).</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1229 ","pages":"Article 123865"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10569937","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":"Adaptation of the AbsoluteIDQ p180 kit to the analysis of metabolites in the human aqueous humor","authors":"Karolina Pietrowska ,&nbsp;Adrian Godlewski ,&nbsp;Emil Grochowski ,&nbsp;Wioleta Gosk ,&nbsp;Joanna Konopinska ,&nbsp;Adam Kretowski ,&nbsp;Michal Ciborowski ,&nbsp;Diana Dmuchowska","doi":"10.1016/j.jchromb.2023.123880","DOIUrl":"10.1016/j.jchromb.2023.123880","url":null,"abstract":"<div><p>The aim of this study was to use the commercial kit Absolute<em>IDQ</em> p180 (Biocrates) for the quantification of metabolites in aqueous humor (AH), as well as to determine the optimal volume of AH that is necessary to obtain reliable and reproducible results. Different volumes of AH (10 µl, 20 µl, and 30 µl) were tested. Of the 188 metabolites measurable with the Biocrates kit, 69 were detected in AH. Depending on the volume used, 41, 51, and 63 metabolites were measured using 10 µl, 20 µl, and 30 µl of AH, respectively. The repeatability of the measurements improved with increasing AH volume. Considering only those metabolites that were obtained with a CV &lt; 15%, 34 metabolites at 10 µl, 41 at 20 µl, and 44 at 30 µl AH were received. On this basis, it can be concluded that the tested method can be successfully applied to analyze metabolites in the human AH. To achieve the most comprehensive detection range and highest repeatability of measurements, it is recommended to use 30 µl AH.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1229 ","pages":"Article 123880"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570023223002908/pdfft?md5=cc60c4669083fbc0b4bf86d89e2ef6c4&pid=1-s2.0-S1570023223002908-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10569939","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":"Liquid chromatography-tandem mass spectrometry based simultaneous quantification of tryptophan, serotonin and kynurenine pathway metabolites in tissues and cell culture systems","authors":"Dennis Fröbel,&nbsp;Daniela Stanke,&nbsp;Mathias Langner,&nbsp;Gintare Žygienė,&nbsp;Nicole Bechmann,&nbsp;Mirko Peitzsch","doi":"10.1016/j.jchromb.2023.123870","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123870","url":null,"abstract":"<div><h3>Background</h3><p>Kynurenine and respective metabolites exhibit bioactivity as well as tryptophan, an essential amino acid, and the neurotransmitter serotonin. Dysregulations in the kynurenine pathway are involved in neurodegenerative/neuropsychiatric disorders and diabetes mellitus type 2 but also in cancer. Therefore, measurements of kynurenine-related metabolites will improve the general understanding for kynurenine pathway relevance in disease pathogenesis.</p></div><div><h3>Methods</h3><p>Tryptophan, serotonin, picolinic acid, quinolinic acid, 3–OH-kynurenine, kynurenine, 3-OH-anthranilic acid, kynurenic acid, anthranilic acid as well as nicotinic acid and the redox cofactor NAD⁺ were analyzed in heterogeneous matrices by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After validation, the described method was applied for measurements of native metabolite concentrations in murine tissues and cellular systems including pathway-shift monitoring after treatment with the tryptophan-2,3-dioxygenase-inhibitor 680C91. In addition, the method was evaluated for its ability for integration into multi-omics approaches using a single sample metabolite extraction procedure.</p></div><div><h3>Results</h3><p>A simple and sensitive UPLC-MS/MS method for simultaneous quantification of up to 10 kynurenine-related metabolites in four biological matrices was developed. Within a run time of 6.5 min, chromatographic separation of kynurenine-related metabolites, including the isomers nicotinic acid and picolinic acid, was achieved without derivatization. Validation parameters, including interday precision (&lt;14.8%), mean accuracy (102.4% ± 12.9%) and linear detection ranges of more than three orders of magnitude, indicate method reliability. Depending the investigated sample matrix, the majority of metabolites were successfully detected and quantified in native murine and cell culture derived sample materials. Furthermore, the method allowed to monitor the impact of a tryptophan-2,3-dioxygenase-inhibitor on kynurenine pathway in a cellular system and is suitable for multi-assay analyses using aliquots from the same cell extract.</p></div><div><h3>Conclusion</h3><p>The described UPLC-MS/MS method provides a simple tool for the simultaneous quantification of kynurenine pathway metabolites. Due to its suitability for many physiological matrices, the method provides wide application for disease-related experimental settings.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1229 ","pages":"Article 123870"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3146972","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}