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

{"title":"The VALIDity of laboratory developed tests: Leave it to the experts?","authors":"Mark A. Marzinke , William Clarke , Dennis J. Dietzen , Andrew N. Hoofnagle , Gwendolyn A. McMillin , Maria Alice V. Willrich","doi":"10.1016/j.jmsacl.2022.12.002","DOIUrl":"10.1016/j.jmsacl.2022.12.002","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/7f/main.PMC9755360.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10372054","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 of Tier 2 LC-MRM-MS protein quantification methods for liquid biopsies","authors":"Nina Diederiks ,&nbsp;Cor J. Ravensbergen ,&nbsp;Maxim Treep ,&nbsp;Madelein van Wezel ,&nbsp;Matt Kuruc ,&nbsp;L. Renee Ruhaak ,&nbsp;Rob A.E.M. Tollenaar ,&nbsp;Christa M. Cobbaert ,&nbsp;Yuri E.M. van der Burgt ,&nbsp;Wilma E. Mesker","doi":"10.1016/j.jmsacl.2022.12.007","DOIUrl":"10.1016/j.jmsacl.2022.12.007","url":null,"abstract":"<div><p>In the pursuit of personalized diagnostics and tailored treatments, quantitative protein tests contribute to a more precise definition of health and disease. The development of new quantitative protein tests should be driven by an unmet clinical need and performed in a collaborative effort that involves all stakeholders. With regard to the analytical part, mass spectrometry (MS)-based platforms are an excellent tool for quantification of specific proteins in body fluids, for example focused on cancer. The obtained readouts have great potential in determining tumor aggressiveness to facilitate treatment decisions, and can furthermore be used to monitor patient response. Internationally standardized TNM classifications of malignant tumors are beneficial for diagnosis, however treatment outcome and survival of cancer patients is poorly predicted. To this end, the importance of the tumor microenvironment has endorsed the introduction of the tumor-stroma ratio as a prognostic parameter in solid primary tumor types. Currently, the stromal content of tumor tissues is determined via routine diagnostic pathology slides. With the development of liquid chromatography (LC)-MS methods we aim at quantification of tumor-stroma specific proteins in body fluids. In this mini-review the analytical aspect of this developmental trajectory is further detailed.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/59/main.PMC9811211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10506333","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":"A distributable LC-MS/MS method for the measurement of serum thyroglobulin","authors":"Junyan Shi ,&nbsp;William S. Phipps ,&nbsp;Benjamin Y. Owusu ,&nbsp;Clark M. Henderson ,&nbsp;Thomas J. Laha ,&nbsp;Jessica O. Becker ,&nbsp;Morteza Razavi ,&nbsp;Michelle A. Emrick ,&nbsp;Andrew N. Hoofnagle","doi":"10.1016/j.jmsacl.2022.09.005","DOIUrl":"10.1016/j.jmsacl.2022.09.005","url":null,"abstract":"<div><h3>Background</h3><p>Despite its clear advantages over immunoassay-based testing, the measurement of serum thyroglobulin by mass spectrometry remains limited to a handful of institutions. Slow adoption by clinical laboratories could reflect limited accessibility to existing methods that have sensitivity comparable to modern immunoassays, as well as a lack of tools for calibration and assay harmonization.</p></div><div><h3>Methods</h3><p>We developed and validated a liquid chromatography-tandem mass spectrometry-based assay for the quantification of serum thyroglobulin. The protocol combined peptide immunoaffinity purification using a commercially available, well-characterized monoclonal antibody and mobile phase modification with dimethylsulfoxide (DMSO) for enhanced sensitivity. To facilitate harmonization with other laboratories, we developed a novel, serum-based 5-point distributable reference material (Husky Ref).</p></div><div><h3>Results</h3><p>The assay demonstrated a lower limit of quantification of 0.15 ng/mL (&lt;20 %CV). Mobile phase DMSO increased signal intensity of the target peptide at least 3-fold, improving quantification at low concentrations. Calibration traceable to Husky Ref enabled harmonization between laboratories in an interlaboratory study.</p></div><div><h3>Conclusions</h3><p>Sensitive mass spectrometry-based thyroglobulin measurement can be achieved using a monoclonal antibody during peptide immunoaffinity purification and the addition of mobile phase DMSO. Laboratories interested in deploying this assay can utilize the provided standard operating procedure and freely-available Husky Ref reference material.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/89/main.PMC9641599.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691428","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 “Instability of 7-aminoclonazepam in frozen storage conditions” [Clin. Mass Spectrom. 9 (2018) 23–24]","authors":"Jayme L. Dahlin ,&nbsp;Athena K. Petrides","doi":"10.1016/j.jmsacl.2022.09.006","DOIUrl":"10.1016/j.jmsacl.2022.09.006","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/89/main.PMC9516442.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40393723","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":"Advances in MS instrumentation: The present and future of the clinical lab","authors":"Christopher D. Chouinard","doi":"10.1016/j.jmsacl.2022.08.003","DOIUrl":"10.1016/j.jmsacl.2022.08.003","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/e9/main.PMC9641583.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691427","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":"Validation of atovaquone plasma levels by liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring in pediatric patients","authors":"Thomas D. Horvath ,&nbsp;Izmarie Poventud-Fuentes ,&nbsp;Lily Olayinka ,&nbsp;Asha James ,&nbsp;Sigmund J. Haidacher ,&nbsp;Kathleen M. Hoch ,&nbsp;Alexandra M. Stevens ,&nbsp;Anthony M. Haag ,&nbsp;Sridevi Devaraj","doi":"10.1016/j.jmsacl.2022.09.004","DOIUrl":"10.1016/j.jmsacl.2022.09.004","url":null,"abstract":"<div><h3>Background</h3><p>Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.</p></div><div><h3>Methods</h3><p>Atovaquone was extracted from a 10 µL volume of K₂-EDTA human plasma using a solution consisting of ACN: EtOH: DMF (8:1:1 v:v:v), separated using reverse-phase chromatography, and detected using a SCIEX 5500 QTrap MS system. LC-MS/MS assay performance was evaluated for precision, accuracy, carryover, sensitivity, specificity, linearity, and interferences.</p></div><div><h3>Results</h3><p>Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min per injection, and retention times of 4.3 min. Atovaquone was measured over a dynamic concentration range of 0.63 – 80 µM with a deviation within ≤ ± 5.1 % of the target value. Intra- and inter-assay precision were ≤ 2.7 % and ≤ 8.4 %, respectively. Dilutional, carryover, and interference studies were also within acceptable limits.</p></div><div><h3>Conclusions</h3><p>Our studies have shown that our LC-MS/MS-based method is both reliable and robust for the quantification of plasma atovaquone concentrations and can be used to determine the effective dose of atovaquone for pediatric patients treated for AML.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/80/main.PMC9641598.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691429","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":"Imaging mass spectrometry reveals complex lipid distributions across Staphylococcus aureus biofilm layers","authors":"Emilio S. Rivera ,&nbsp;Andy Weiss ,&nbsp;Lukasz G. Migas ,&nbsp;Jeffrey A. Freiberg ,&nbsp;Katerina V. Djambazova ,&nbsp;Elizabeth K. Neumann ,&nbsp;Raf Van de Plas ,&nbsp;Jeffrey M. Spraggins ,&nbsp;Eric P. Skaar ,&nbsp;Richard M. Caprioli","doi":"10.1016/j.jmsacl.2022.09.003","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2022.09.003","url":null,"abstract":"<div><h3>Introduction</h3><p>Although <em>Staphylococcus aureus</em> is the leading cause of biofilm-related infections, the lipidomic distributions within these biofilms is poorly understood. Here, lipidomic mapping of <em>S. aureus</em> biofilm cross-sections was performed to investigate heterogeneity between horizontal biofilm layers.</p></div><div><h3>Methods</h3><p><em>S. aureus</em> biofilms were grown statically, embedded in a mixture of carboxymethylcellulose/gelatin, and prepared for downstream matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS). Trapped ion mobility spectrometry (TIMS) was also applied prior to mass analysis.</p></div><div><h3>Results</h3><p>Implementation of TIMS led to a ∼ threefold increase in the number of lipid species detected. Washing biofilm samples with ammonium formate (150 mM) increased signal intensity for some bacterial lipids by as much as tenfold, with minimal disruption of the biofilm structure. MALDI TIMS IMS revealed that most lipids localize primarily to a single biofilm layer, and species from the same lipid class such as cardiolipins CL(57:0) – CL(66:0) display starkly different localizations, exhibiting between 1.5 and 6.3-fold intensity differences between layers (n = 3, p &lt; 0.03). No horizontal layers were observed within biofilms grown anaerobically, and lipids were distributed homogenously.</p></div><div><h3>Conclusions</h3><p>High spatial resolution analysis of <em>S. aureus</em> biofilm cross-sections by MALDI TIMS IMS revealed stark lipidomic heterogeneity between horizontal <em>S. aureus</em> biofilm layers demonstrating that each layer was molecularly distinct. Finally, this workflow uncovered an absence of layers in biofilms grown under anaerobic conditions, possibly indicating that oxygen contributes to the observed heterogeneity under aerobic conditions. Future applications of this workflow to study spatially localized molecular responses to antimicrobials could provide new therapeutic strategies.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X22000372/pdfft?md5=5cfe45d904dd71d41d3a2372d5f7f9aa&pid=1-s2.0-S2667145X22000372-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92006234","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":"LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring","authors":"Mirjana Radovanovic ,&nbsp;Richard O. Day ,&nbsp;Graham D.R. Jones ,&nbsp;Peter Galettis ,&nbsp;Ross L.G. Norris","doi":"10.1016/j.jmsacl.2022.11.001","DOIUrl":"10.1016/j.jmsacl.2022.11.001","url":null,"abstract":"<div><h3>Background</h3><p>Optimizing antimicrobial therapy to attain drug exposure that limits the emergence of resistance, effectively treats the infection, and reduces the risk of side effects is of a particular importance in critically ill patients, in whom normal functions are augmented or/and are infected with pathogens less sensitive to treatment. Achievement of these goals can be enhanced by therapeutic drug monitoring (TDM) for many antibiotics. A liquid chromatography tandem mass spectrometry (LC–MS/MS) method is presented here for simultaneous quantification of ten antimicrobials: cefazolin (CZO), cefepime (CEP), cefotaxime (CTA), ceftazidime (CTZ), ciprofloxacin (CIP), flucloxacillin (FLU), linezolid (LIN), meropenem (MER), piperacillin (PIP) and tazobactam (TAZ) in human plasma.</p></div><div><h3>Methods</h3><p>Plasma samples were precipitated with acetonitrile and injected into the LC–MS/MS. Chromatographic separation was on a Waters Acquity BEH C₁₈ column. Compounds were eluted with water and acetonitrile containing 0.1 % formic acid, using a gradient (0.5–65 % B), in 3.8 min. The flow rate was 0.4 mL/min, and the run time was 5.8 min.</p></div><div><h3>Results</h3><p>The calibration curves were linear across the tested concentration ranges (0.5–250, CZO, CEP, CTA, CTZ and FLU; 0.2–100, MER and TAZ; 0.1–50, CIP and LIN and 1–500 mg/L, PIP). The intra and inter-day imprecision was &lt; 11 %. Accuracy ranged from 95 to 114 %. CTZ and MER showed ionization suppression while CIP showed ionization enhancement, which was normalized with the use of the internal standard.</p></div><div><h3>Conclusion</h3><p>An LC–MS/MS method for simultaneous quantification of ten antimicrobials in human plasma was developed for routine TDM.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/77/main.PMC9756784.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10750302","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 application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum","authors":"Yu Zhang ,&nbsp;John C. Halifax ,&nbsp;Christina Tangsombatvisit ,&nbsp;Cassandra Yun ,&nbsp;Shaokun Pang ,&nbsp;Shirin Hooshfar ,&nbsp;Alan H.B. Wu ,&nbsp;Kara L. Lynch","doi":"10.1016/j.jmsacl.2022.07.005","DOIUrl":"10.1016/j.jmsacl.2022.07.005","url":null,"abstract":"<div><h3>Introduction</h3><p>The use of illicitly manufactured synthetic opioids, specifically fentanyl and its analogs, has escalated exponentially in the United States over the last decade. Due to the targeted nature of drug detection methods in clinical laboratories and the ever-evolving list of synthetic opioids of concern, alternative analytical approaches are needed.</p></div><div><h3>Methods</h3><p>Using the fentanyl analog screening (FAS) kit produced by the Centers for Disease Control and Prevention (CDC), we developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) synthetic opioid spectral library and data acquisition method using information dependent acquisition of product ion spectra. Chromatographic retention times, limits of detection and matrix effects, in urine and serum, for the synthetic opioids in the FAS kit (n = 150) were established. All urine and serum specimens sent to a clinical toxicology laboratory for comprehensive drug testing in 2019 (n = 856) and 2021 (n = 878) were analyzed with the FAS LC-HRMS library to determine the prevalence of fentanyl analogs and other synthetic opioids, retrospectively (2019) and prospectively (2021).</p></div><div><h3>Results</h3><p>The limit of detection (LOD) of each opioid ranged from 1 to 10 ng/mL (median, 2.5 ng/mL) in urine and 0.25–2.5 ng/mL (median, 0.5 ng/mL) in serum. Matrix effects ranged from −79 % to 86 % (median, −37 %) for urine, following dilution and direct analysis, and −80 % to 400 % (median, 0 %) for serum, following protein precipitation. The prevalence of fentanyl/fentanyl analogs in serum samples increased slightly from 2019 to 2021 while it remained the same in urine. There were only 2 samples identified that contained a fentanyl analog without the co-occurrence of fentanyl or fentanyl metabolites. Analysis of the established MS/MS spectral library revealed characteristic fragmentation patterns in most fentanyl analogs, which can be used for structure elucidation and drug identification of future analogs.</p></div><div><h3>Conclusions</h3><p>The LC-HRMS method was capable of detecting fentanyl analogs in routine samples sent for comprehensive drug testing. The method can be adapted to accommodate testing needs for the evolving opioid epidemic.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/d5/main.PMC9440429.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40352875","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 “Migration from RIA to LC-MS/MS for aldosterone determination: Implications for clinical practice and determination of plasma and urine reference range intervals in a cohort of healthy Belgian subjects” [Clin. Mass Spectrom. 9 (2018) 7–17]","authors":"Caroline M. Le Goff ,&nbsp;Ana Gonzalez-Antuña ,&nbsp;Stéphanie D. Peeters ,&nbsp;Neus Fabregat-Cabello ,&nbsp;Jessica G. Van Der Gugten ,&nbsp;Laurent Vroonen ,&nbsp;Hans Pottel ,&nbsp;Daniel T. Holmes ,&nbsp;Etienne Cavalier","doi":"10.1016/j.jmsacl.2022.10.001","DOIUrl":"10.1016/j.jmsacl.2022.10.001","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/aa/main.PMC9619187.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464119","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}