Journal of Mass Spectrometry and Advances in the Clinical Lab最新文献

{"title":"Corrigendum to “Mass spectrometry for therapeutic drug monitoring of anti-tuberculosis drugs” [Clin. Mass Spectrom. 14(Part A) (2019) 34–45]","authors":"Johanna Kuhlin , Marieke G.G. Sturkenboom , Samiksha Ghimire , Ioana Margineanu , Simone H.J. van den Elsen , Noviana Simbar , Onno W. Akkerman , Erwin M. Jongedijk , Remco A. Koster , Judith Bruchfeld , Daan J. Touw , Jan-Willem C. Alffenaar","doi":"10.1016/j.jmsacl.2022.08.001","DOIUrl":"10.1016/j.jmsacl.2022.08.001","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Page 72"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/f5/main.PMC9400071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33444768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplexed quantification of insulin and C-peptide by LC-MS/MS without the use of antibodies","authors":"North Foulon ,&nbsp;Elisha Goonatilleke ,&nbsp;Michael J. MacCoss ,&nbsp;Michelle A. Emrick ,&nbsp;Andrew N. Hoofnagle","doi":"10.1016/j.jmsacl.2022.06.003","DOIUrl":"10.1016/j.jmsacl.2022.06.003","url":null,"abstract":"<div><h3>Introduction</h3><p>The measurement of insulin and C-peptide provides a valuable tool for the clinical evaluation of hypoglycemia. In research, these biomarkers are used together to better understand hyperinsulinemia, hepatic insulin clearance, and beta cell function. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an attractive approach for the analysis of insulin and C-peptide because the platform is specific, can avoid certain limitations of immunoassays, and can be multiplexed. Previously described LC-MS/MS methods for the simultaneous quantification of insulin and C-peptide measure the intact analytes and most have relied on immunoaffinity enrichment. These approaches can be limited in terms of sensitivity and interference from auto-antibodies, respectively. We have developed a novel method that does not require antibodies and uses proteolytic digestion to yield readily ionizable proteotypic peptides that enables the sensitive, specific, and simultaneous quantitation of insulin and C-peptide.</p></div><div><h3>Methods</h3><p>Serum samples were precipitated with acetonitrile. Analytes were enriched using solid phase extraction and then digested with endoproteinase Glu-C. Surrogate peptides for insulin and C-peptide were analyzed using targeted LC-MS/MS.</p></div><div><h3>Results</h3><p>Inter-day imprecision was below 20 %CV and linearity was observed down to the lower limit of quantitation for both analytes (insulin = 0.09 ng/mL, C-peptide = 0.06 ng/mL). Comparison to a commercially available insulin immunoassay (Beckman Coulter UniCel DxI 600 Access) revealed a 30% bias between methods.</p></div><div><h3>Conclusion</h3><p>A novel LC-MS/MS method for the simultaneous analysis of insulin and C-peptide using Glu-C digestion was developed and evaluated. A detailed standard operating procedure is provided to help facilitate implementation in other laboratories.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Pages 19-26"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/9e/main.PMC9207678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40238936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitation of non-derivatized free amino acids for detecting inborn errors of metabolism by incorporating mixed-mode chromatography with tandem mass spectrometry","authors":"Patrick D. DeArmond ,&nbsp;Dustin R. Bunch","doi":"10.1016/j.jmsacl.2022.05.002","DOIUrl":"10.1016/j.jmsacl.2022.05.002","url":null,"abstract":"<div><h3>Introduction</h3><p>Amino acids are critical biomarkers for many inborn errors of metabolism, but amino acid analysis is challenging due to the range of chemical properties inherent in these small molecules. Techniques are available for amino acid analysis, but they can suffer from long run times, laborious derivatization, and/or poor resolution of isobaric compounds.</p></div><div><h3>Objective</h3><p>To develop and validate a method for the quantitation of a non-derivatized free amino acid profile in both plasma and urine samples using mixed-mode chromatography and tandem mass spectrometry.</p></div><div><h3>Methods</h3><p>Chromatographic conditions were optimized to separate leucine, isoleucine, and allo-isoleucine and maintain analytical runtime at less than 15 min. Sample preparation included a quick protein precipitation followed by LC-MS/MS analysis. Matrix effects, interferences, linearity, carryover, acceptable dilution limits, precision, accuracy, and stability were evaluated in both plasma and urine specimen types.</p></div><div><h3>Results</h3><p>A total of 38 amino acids and related compounds were successfully quantitated with this method. In addition, argininosuccinic acid was qualitatively analyzed. A full clinical validation was performed that included method comparison to a reference laboratory for plasma and urine with Deming regression slopes ranging from 0.38 to 1.26.</p></div><div><h3>Conclusion</h3><p>This method represents an alternative to derivatization-based methods, especially in urine samples where interference from metabolites and medications is prevalent.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Pages 1-11"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X22000153/pdfft?md5=d9c392ee9a08d22e45e619410635f8bc&pid=1-s2.0-S2667145X22000153-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76651043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted metabolic profiling of urinary steroids with a focus on analytical accuracy and sample stability","authors":"Nora Vogg ,&nbsp;Tobias Müller ,&nbsp;Andreas Floren ,&nbsp;Thomas Dandekar ,&nbsp;Oliver Scherf-Clavel ,&nbsp;Martin Fassnacht ,&nbsp;Matthias Kroiss ,&nbsp;Max Kurlbaum","doi":"10.1016/j.jmsacl.2022.07.006","DOIUrl":"10.1016/j.jmsacl.2022.07.006","url":null,"abstract":"<div><h3>Introduction</h3><p>Preoperative diagnostic workup of adrenal tumors is based on imaging and hormone analyses, but charged with uncertainties. Steroid profiling by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 24-h urine has shown potential to discriminate benign and malignant adrenal tumors. Our aim was to develop and validate a specific and accurate LC-MS/MS method for the quantification of deconjugated urinary marker steroids, to evaluate their pre-analytical stability and to apply the method to clinical samples of patients with adrenal tumors.</p></div><div><h3>Methods</h3><p>A method for the quantification of 11 deconjugated steroids (5-pregnenetriol, dehydroepiandrosterone, cortisone, cortisol, α-cortolone, tetrahydro-11-deoxycortisol, etiocholanolone, pregnenolone, pregnanetriol, pregnanediol, and 5-pregnenediol) in human urine was developed and validated based on international guidelines. Steroids were enzymatically deconjugated and extracted by solid phase extraction before LC-MS/MS quantification in positive electrospray ionization mode.</p></div><div><h3>Results</h3><p>Excellent linearity with R² &gt; 0.99 and intra- and inter-day precisions of &lt; 10.1 % were found. Relative matrix effects were between 96.4 % and 101.6 % and relative recovery was between 98.2 % and 115.0 %. Sufficient pre-freeze stability for all steroids in urine was found at 20–25 °C for seven days and at 4–6 °C for up to 28 days. Samples were stable during long-term storage at −20 °C and −80 °C for 6 months.</p></div><div><h3>Conclusions</h3><p>A sensitive and robust LC-MS/MS method for the quantification of 11 urinary steroids was developed and validated according to international guidelines. Pre-analytical matrix stability was evaluated and the suitability of the method for the analysis of clinical samples and prospective validation studies was shown.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Pages 44-52"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/df/main.PMC9334310.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40589851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Haptoglobin polymorphism affects its N-glycosylation pattern in serum","authors":"M. Kohansal-Nodehi,&nbsp;M. Swiatek-de Lange,&nbsp;G. Tabarés,&nbsp;H. Busskamp","doi":"10.1016/j.jmsacl.2022.07.001","DOIUrl":"10.1016/j.jmsacl.2022.07.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Haptoglobin (Hp) is an abundant acute-phase protein secreted mainly by the liver into the bloodstream. There are three Hp protein phenotypes (Hp type 1–1, 2–1, and 2–2), which differ in the number of α- and β-chains, type of α-chain (the β-chain type remains the same in all the Hp phenotypes), and the polymers that they form via disulfide bonds. Hp has four N-glycosylation sites on the β-chain. Glycosylation of Hp has been reported frequently as a potential glycobiomarker for many diseases; however, whether Hp polymorphism affects its glycosylation has not yet been addressed extensively or in depth.</p></div><div><h3>Objectives</h3><p>This study investigated the differences between the glycosylation patterns of Hp phenotypes using serum from 12 healthy individuals (four for each Hp phenotype).</p></div><div><h3>Method</h3><p>An efficient method for isolating Hp from serum was established and subsequently the Hp phenotype of each sample was characterized by immunoblotting. Then, LC-MS/MS analysis of isolated Hp after treatment with three exoglycosidases (sialidase, α2-3 neuraminidase, Endo F3) was performed to characterize the glycosylation pattern of Hp for each individual sample.</p></div><div><h3>Results</h3><p>The data reveal significant differences among the branching, sialylation, and fucosylation of Hp types, documenting the effect of Hp polymorphism on its glycosylation.</p></div><div><h3>Conclusion</h3><p>Overall, the study suggests that Hp phenotype characterization should be considered during the investigation of Hp glycosylation.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Pages 61-70"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/08/main.PMC9352458.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40594166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Analytical validation of protein biomarkers for risk of spontaneous preterm birth” [Clin. Mass Spectrom. 3 (2017) 25–38]","authors":"Chad Bradford ,&nbsp;Rob Severinsen ,&nbsp;Trina Pugmire ,&nbsp;Matison Rasmussen ,&nbsp;Kathryn Stoddard ,&nbsp;Yuta Uemura ,&nbsp;Spencer Wheelwright ,&nbsp;Marija Mentinova ,&nbsp;Daniel Chelsky ,&nbsp;Stephen W. Hunsucker ,&nbsp;Paul Kearney ,&nbsp;Durlin Hickok ,&nbsp;Tracey C. Fleischer ,&nbsp;Ilia Ichetovkin ,&nbsp;J. Jay Boniface ,&nbsp;Gregory C. Critchfield ,&nbsp;John M. Peltier","doi":"10.1016/j.jmsacl.2022.07.007","DOIUrl":"10.1016/j.jmsacl.2022.07.007","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Page 71"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/4b/main.PMC9372730.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40700462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discs","authors":"Ignacio Guillermo Bressán ,&nbsp;María Isabel Giménez ,&nbsp;Susana Francisca Llesuy","doi":"10.1016/j.jmsacl.2022.06.002","DOIUrl":"10.1016/j.jmsacl.2022.06.002","url":null,"abstract":"<div><h3>Introduction</h3><p>Advances in liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) have enabled the quantification of immunosuppressants using microsampling techniques. In this context, dried matrix on paper discs (DMPD) could be a useful alternative to conventional venipuncture. Although analytical validation is necessary to establish the suitability of method performance, it is not sufficient to proceed with its implementation into routine clinical practice. Also necessary is that equivalence between sampling methods be demonstrated in a clinical validation study.</p></div><div><h3>Objetives</h3><p>To clinically validate a LC-MS/MS method for the quantification of tacrolimus, sirolimus, everolimus and cyclosporin A using DMPD.</p></div><div><h3>Methods</h3><p>According to the recommendations of international guidelines, at least 40 whole blood (WB) and DMPD paired samples for each analyte were collected by skilled technicians and analyzed using LC-MS/MS. Results were evaluated in terms of statistical agreement and bias values at medical decision points.</p></div><div><h3>Results</h3><p>For all analytes, Passing-Bablok regression analysis revealed that confidence intervals (CIs) for slopes and intercepts included 1 and 0, respectively. It also showed that biases at medical decision points were not clinically relevant. No statistically significant differences between DMPD and WB were found using difference plots and agreement analysis. In this regard, CIs for bias estimators included 0, and more than 95% of the results fell within the limits of agreement.</p></div><div><h3>Conclusion</h3><p>The feasibility of the clinical application of simultaneous quantification of tacrolimus, sirolimus, everolimus and cyclosporin A in DMPD was demonstrated. Results showed that this microsampling technique is interchangeable with conventional WB sampling when specimens are collected by trained personnel.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Pages 12-18"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X22000177/pdfft?md5=1bfb6b7c19afa801057c5b82bc6a4d1e&pid=1-s2.0-S2667145X22000177-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73369821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry","authors":"Erik I. Hallin ,&nbsp;Trond Trætteberg Serkland ,&nbsp;Kjell-Morten Myhr ,&nbsp;Øivind Torkildsen ,&nbsp;Silje Skrede","doi":"10.1016/j.jmsacl.2022.07.004","DOIUrl":"10.1016/j.jmsacl.2022.07.004","url":null,"abstract":"<div><h3>Introduction</h3><p>Ocrelizumab is a monoclonal anti-CD20 antibody approved for the treatment of multiple sclerosis (MS). The clinical value of therapeutic drug monitoring (TDM) for this antibody in treatment of MS is unknown, and an adequately specific and precise quantitation method for ocrelizumab in patient serum could facilitate investigation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantitation methods have been shown to have higher analytic specificity and precision than enzyme-linked immunosorbent assays.</p></div><div><h3>Objectives</h3><p>To establish and validate an LC-MS/MS-based quantitation method for ocrelizumab.</p></div><div><h3>Methods</h3><p>We present an LC-MS/MS-based quantitation method using immunocapture purification followed by trypsinization and analysis by a triple quadrupole mass analyzer obtaining results within the same day.</p></div><div><h3>Results</h3><p>We found that the ocrelizumab peptide GLEWVGAIYPGNGDTSYNQK (Q1/Q3 Quantifier ion: 723.68³⁺/590.77 y11²⁺ Qualifier ion: 723.68³⁺/672.30 y12²⁺) can be used for quantitation and thereby developed a method for quantifying ocrelizumab in human serum with a quantitation range of 1.56 to 200 µg/mL. The method was validated in accordance with EMA requirements in terms of selectivity, carry-over, lower limit of quantitation, calibration curve, accuracy, precision and matrix effect. Ocrelizumab serum concentrations were measured in three MS patients treated with ocrelizumab, immediately before and after ocrelizumab infusion, with additional sampling after 2, 4, 8 and 12 weeks. Measured serum concentrations of ocrelizumab showed expected values for both Cmax and drug half-life over the sampled time period.</p></div><div><h3>Conclusion</h3><p>We have established a reliable quantitation method for serum ocrelizumab that can be applied in clinical studies, facilitating the evaluation of ocrelizumab TDM in MS.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Pages 53-60"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6c/74/main.PMC9334332.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40589849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a paper spray mass spectrometry method for the rapid quantitation of remdesivir and its active metabolite, GS-441524, in human plasma","authors":"Christine Skaggs ,&nbsp;Hannah Zimmerman ,&nbsp;Nicholas Manicke ,&nbsp;Lindsey Kirkpatrick","doi":"10.1016/j.jmsacl.2022.06.001","DOIUrl":"10.1016/j.jmsacl.2022.06.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Remdesivir (GS-5734) is a nucleoside analog prodrug with antiviral activity against several single-stranded RNA viruses, including the novel severe respiratory distress syndrome virus 2 (SARS-CoV-2). It is currently the only FDA-approved antiviral agent for the treatment of individuals with COVID-19 caused by SARS-CoV-2. However, remdesivir pharmacokinetics/pharmacodynamics (PK/PD) and toxicity data in humans are extremely limited. It is imperative that precise analytical methods for the quantification of remdesivir and its active metabolite, GS-441524, are developed for use in further studies. We report, herein, the first validated anti-viral paper spray-mass spectrometry (PS-MS/MS) assay for the quantification of remdesivir and GS-441524 in human plasma. We seek to highlight the utility of PS-MS/MS technology and automation advancements for its potential future use in clinical research and the clinical laboratory setting.</p></div><div><h3>Methods</h3><p>Calibration curves for remdesivir and GS-441524 were created utilizing seven plasma-based calibrants of varying concentrations and two isotopic internal standards of set concentrations. Four plasma-based quality controls were prepared in a similar fashion to the calibrants and utilized for validation. No sample preparation was needed. Briefly, plasma samples were spotted on a paper substrate contained within pre-manufactured plastic cassette plates, and the spots were dried for 1 h. The samples were then analyzed directly for 1.2 min utilizing PS-MS/MS. All experiments were performed on a Thermo Scientific Altis triple quadrupole mass spectrometer utilizing automated technology.</p></div><div><h3>Results</h3><p>The calibration ranges were 20 – 5000 and 100 – 25000 ng/mL for remdesivir and GS-441524, respectively. The calibration curves for the two antiviral agents showed excellent linearity (average R² = 0.99–1.00). The inter- and intra-day precision (%CV) across validation runs at four QC levels for both analytes was less than 11.2% and accuracy (%bias) was within ± 15%. Plasma calibrant stability was assessed and degradation for the 4 °C and room temperature samples were seen beginning at Day 7. The plasma calibrants were stable at −20 °C. No interference, matrix effects, or carryover was discovered during the validation process.</p></div><div><h3>Conclusions</h3><p>PS-MS/MS represents a useful methodology for rapidly quantifying remdesivir and GS-441524, which may be useful for clinical PK/PD, therapeutic drug monitoring (TDM), and toxicity assessment, particularly during the current COVID-19 pandemic and future viral outbreaks.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Pages 27-35"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/93/b8/main.PMC9188284.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9835437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simple, high-throughput measurement of gut-derived short-chain fatty acids in clinically relevant biofluids using gas chromatography-mass spectrometry","authors":"Joshua T Bain ,&nbsp;Maarten W Taal ,&nbsp;Nicholas M Selby ,&nbsp;James C Reynolds ,&nbsp;Liam M Heaney","doi":"10.1016/j.jmsacl.2022.07.002","DOIUrl":"10.1016/j.jmsacl.2022.07.002","url":null,"abstract":"<div><h3>Introduction</h3><p>The quantitative measurement of circulating gut bacteria-derived metabolites has increased in recent years due to their associations with health and disease. While much of the previous attention has been placed on metabolites considered as deleterious to health, a shift to the investigation of short-chain fatty acids (SCFAs) as potential health promotors has been observed.</p></div><div><h3>Objectives</h3><p>To develop a simple, high-throughput and quantitative assay to measure gut-derived SCFAs in clinically relevant biofluids using gas chromatography-mass spectrometry (GC–MS).</p></div><div><h3>Methods</h3><p>A short (7.5 min) GC–MS assay was optimized for measurement of seven straight- and branched-chain SCFAs and their deuterated isotopes using a wax-based column for analysis without prior derivatization. The assay was validated using routine criteria to assess precision, accuracy, matrix effects, recovery, and extraction reproducibility. Assay applicability was tested in cohorts of healthy individuals and kidney disease patients.</p></div><div><h3>Results</h3><p>The assay was demonstrated to be precise, accurate and reproducible with acceptable levels of matrix effect and analyte recovery. Lower limits of detection and quantitation were in the low ng/mL range. An investigation into different blood collection tube chemistries demonstrated that lithium heparin plasma and serum clotting activator tubes are recommended for use in future cross-study comparisons. Kidney disease patient analyses demonstrated variable differences across SCFAs when comparing hemodialysis to earlier stages of chronic kidney disease, demonstrating the suitability of the assay for translation to clinical analyses.</p></div><div><h3>Conclusion</h3><p>The assay has been validated and identified as reliable for use in larger-scale studies for the analysis of SCFAs in human plasma and serum.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"25 ","pages":"Pages 36-43"},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40620965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}