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

{"title":"Practical considerations for accurate determination of free thyroxine by equilibrium dialysis","authors":"Ashley Ribera ,&nbsp;Li Zhang ,&nbsp;Carla Ribeiro ,&nbsp;Norma Vazquez ,&nbsp;Janet Thonkulpitak ,&nbsp;Julianne C. Botelho ,&nbsp;Uliana Danilenko ,&nbsp;Katleen van Uytfanghe ,&nbsp;Hubert W. Vesper","doi":"10.1016/j.jmsacl.2023.06.001","DOIUrl":"10.1016/j.jmsacl.2023.06.001","url":null,"abstract":"<div><h3>Background</h3><p>Free thyroxine (FT4) measurement is one of the most requested tests in patient care for diagnosing and treating thyroid-related illnesses. Equilibrium dialysis (ED) is considered the “gold standard” for FT4 measurement; however, several factors have a profound effect on the reliability of FT4 assays and require special consideration.</p></div><div><h3>Methods</h3><p>In the current study, we focused on evaluating critical factors that could contribute to reporting errors, such as adsorption of thyroxine (T4) to labware surfaces, stability of serum samples, stock solutions, and calibrator storage conditions, as well as the solvents used to prepare T4 solutions.</p></div><div><h3>Results</h3><p>The adsorption of T4 in ethanolic solutions and dialysates to labware surfaces can be reduced with the careful selection of pipette tips, test tubes, and 96-well plates. Adding pH modifiers to neat T4 solutions can improve its stability. FT4 in serum samples remains stable after exposure to four freeze–thaw cycles, 5 °C for 18–20 h, or −70 °C for a minimum of three years.</p></div><div><h3>Conclusion</h3><p>The presented study has demonstrated that the loss of analyte due to pre-analytical and analytical factors during operation of the FT4 reference measurement procedure (RMP) can be minimized by careful selection of all labware for sample preparation. It was found that the accuracy and imprecision of FT4 assays can be influenced by different types of dialysis devices, but acceptable alternatives to ED membranes were identified. This study demonstrates approaches to establish a FT4 method that is independent from specific suppliers and addresses critical pre-analytical and analytical factors important for FT4 measurements.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"29 ","pages":"Pages 9-15"},"PeriodicalIF":2.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/ed/main.PMC10336244.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199551","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":"Molecular diagnostics and the laboratory developed test: A tale of success and the potential impacts of increased regulation","authors":"Gregory J. Tsongalis","doi":"10.1016/j.jmsacl.2023.01.007","DOIUrl":"10.1016/j.jmsacl.2023.01.007","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 27-29"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/93/f5/main.PMC9941362.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336776","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":"Quantitative tandem mass spectrometry in the clinical laboratory: Regulation and opportunity for validation of laboratory developed tests","authors":"Judith A. Stone ,&nbsp;J. Grace van der Gugten","doi":"10.1016/j.jmsacl.2023.03.001","DOIUrl":"10.1016/j.jmsacl.2023.03.001","url":null,"abstract":"<div><p>Tandem mass spectrometry is an important analytical tool for clinical laboratories, but tests developed and validated in-house (laboratory developed tests, or LDTs) require special consideration. In late 2022, the forecast for United States (U.S.) federal regulation of LDTs changed unexpectedly when the VALID Act was not passed by the U.S. Congress. This Act would have modified the Food and Drug Administration's (FDA's) role to increase regulatory oversight for LDT providers. In this revised context, we review optimization of quantitative mass spectrometry LDT validation and suggest avenues other than an additional FDA mandate to achieve uniform best practice. Common challenges, logistical barriers, and recommendations for easing the burden of best-quality quantitative mass spectrometry LDT method validation are discussed.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 82-90"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/82/main.PMC10017411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9147432","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":"Mass spectrometry quantitation of immunosuppressive drugs in clinical specimens using online solid-phase extraction and accurate-mass full scan-single ion monitoring","authors":"Priscilla S.-W. Yeung ,&nbsp;Paige Miller ,&nbsp;Tran Bao Lai-Nyugen ,&nbsp;Phil Cheng ,&nbsp;Amira Ibrahim ,&nbsp;Run-Zhang Shi ,&nbsp;Raffick A.R. Bowen ,&nbsp;Ruben Yiqi Luo","doi":"10.1016/j.jmsacl.2023.03.002","DOIUrl":"10.1016/j.jmsacl.2023.03.002","url":null,"abstract":"<div><h3>Introduction</h3><p>Therapeutic drug monitoring (TDM) of immunosuppressants is essential for optimal care of transplant patients. Immunoassays and liquid chromatography-mass spectrometry (LC-MS) are the most commonly used methods for TDM. However, immunoassays can suffer from interference from heterophile antibodies and structurally similar drugs and metabolites. Additionally, nominal-mass LC-MS assays can be difficult to optimize and are limited in the number of detectable compounds.</p></div><div><h3>Objectives</h3><p>The aim of this study was to implement a mass spectrometry-based test for immunosuppressant TDM using online solid-phase extraction (SPE) and accurate-mass full scan-single ion monitoring (FS-SIM) data acquisition mode.</p></div><div><h3>Methods</h3><p>LC-MS analysis was performed on a TLX-2 multi-channel HPLC with a Q-Exactive Plus mass spectrometer. TurboFlow online SPE was used for sample clean up. The accurate-mass MS was set to positive electrospray ionization mode with FS-SIM for quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A. MS² fragmentation pattern was used for compound confirmation.</p></div><div><h3>Results</h3><p>The method was validated in terms of precision, analytical bias, limit of quantitation, linearity, carryover, sample stability, and interference. Quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A correlated well with results from an independent reference laboratory (r = 0.926–0.984).</p></div><div><h3>Conclusions</h3><p>Accurate-mass FS-SIM can be successfully utilized for immunosuppressant TDM with good correlation with results generated by standard methods. TurboFlow online SPE allows for a simple “protein crash and shoot” sample preparation protocol. Compared to traditional MRM, analyte quantitation by FS-SIM facilitates a streamlined assay optimization process.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 99-104"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/6b/main.PMC10014293.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152992","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":"Impact of VALID Act implementation on mass spectrometry-based clinical proteomic laboratory developed tests","authors":"Yanchun Lin ,&nbsp;Stefani N. Thomas","doi":"10.1016/j.jmsacl.2023.02.001","DOIUrl":"10.1016/j.jmsacl.2023.02.001","url":null,"abstract":"<div><p>Mass spectrometry (MS)-based clinical proteomic Laboratory Developed Tests (LDTs) for the measurement of protein biomarkers related to endocrinology, cardiovascular disease, cancer, and Alzheimer’s disease are gaining traction in clinical laboratories due to their value in supporting diagnostic and treatment decisions for patients. Under the current regulatory landscape, MS-based clinical proteomic LDTs are regulated by Clinical Laboratory Improvement Amendments (CLIA) under the auspices of the Centers for Medicaid and Medicare Services (CMS). However, should the Verifying Accurate Leading-Edge In Vitro Clinical Test Development (VALID) Act pass, it will grant the FDA greater authority to oversee diagnostic tests, including LDTs. This could impede clinical laboratories' ability to develop new MS-based proteomic LDTs to support existing and emerging patient care needs. Therefore, this review discusses the currently available MS-based proteomic LDTs and their current regulatory landscape in the context of the potential impacts imposed by the passage of the VALID Act.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 30-34"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/8a/main.PMC9971545.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9078218","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":"UTI detection by PCR: Improving patient outcomes","authors":"Brian N. Kelly","doi":"10.1016/j.jmsacl.2023.02.006","DOIUrl":"10.1016/j.jmsacl.2023.02.006","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 60-62"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e8/32/main.PMC9988651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9088010","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 case series evaluation of comprehensive drug testing in the pediatric acute care setting","authors":"Kara L. Lynch","doi":"10.1016/j.jmsacl.2023.02.011","DOIUrl":"10.1016/j.jmsacl.2023.02.011","url":null,"abstract":"<div><h3>Introduction</h3><p>Drug testing typically follows a one-size-fits-all approach that is inadequate in some clinical scenarios, such as child maltreatment, neglect, and unintentional drug exposure. Results from immunoassay-based testing, which are non-specific, insensitive, and far from comprehensive, can lead to unintended consequences for children and their families.</p></div><div><h3>Objectives</h3><p>The objective of this retrospective case series study is to evaluate the utility of real-time (0–1 day) comprehensive drug testing as an alternative to immunoassay-based testing in the pediatric acute care setting.</p></div><div><h3>Methods</h3><p>Comprehensive drug testing results obtained by mass spectrometry testing and associated medical data for all pediatric cases (0–12 years) at one institution from 2019 to 2022 were included in the analysis. The final case series (n = 7) included all cases from patients &lt;3 years with comprehensive drug testing results that were inconsistent with medication history and/or toxicology results by immunoassay.</p></div><div><h3>Results</h3><p>Comprehensive drug testing by mass spectrometry was ordered for 174 urine and blood samples representing 97 patients (0–12 years) from 2019 to 2022. Of these, 76 cases were from patients &lt;3 years old; results were consistent with medication history and confirmatory for immunoassay results (n = 34), consistent with medication history (n = 14), confirmatory for immunoassay results (n = 10), negative (n = 9), or medical history was incomplete (n = 2). The remaining 7 cases were included in the final case series.</p></div><div><h3>Conclusions</h3><p>The cases highlight the value of real-time comprehensive drug testing in acute pediatric cases. Testing results can rule out toxic exposure from the diagnostic differential when negative, and lead to appropriate medical and social interventions when positive.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 75-79"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/ad/main.PMC9995460.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9108719","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":"Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking","authors":"Yuan Lin ,&nbsp;Archana M. Agarwal ,&nbsp;Lissa C. Anderson ,&nbsp;Alan G. Marshall","doi":"10.1016/j.jmsacl.2023.01.004","DOIUrl":"10.1016/j.jmsacl.2023.01.004","url":null,"abstract":"<div><p>β-thalassemia is a quantitative hemoglobin (Hb) disorder resulting in reduced production of Hb A and increased levels of Hb A₂. Diagnosis of β-thalassemia can be problematic when combined with other structural Hb variants, so that the separation approaches in routine clinical centers are not sufficiently decisive to obtain accurate results. Here, we separate the intact Hb subunits by high-performance liquid chromatography, followed by top-down tandem mass spectrometry of intact subunits to distinguish Hb variants. Proton transfer reaction-parallel ion parking (PTR-PIP), in which a radical anion removes protons from multiply charged precursor ions and produces charge-reduced ions spanning a limited <em>m</em>/<em>z</em> range, was used to increase the signal-to-noise ratio of the subunits of interest. We demonstrate that the δ/β ratio can act as a biomarker to identify β-thalassemia in normal electrospray ionization MS1 and PTR-PIP MS1. The application of PTR-PIP significantly increases the sensitivity and specificity of the HPLC-MS method to identify δ/β ratio as a thalassemia biomarker.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 20-26"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/93/66/main.PMC9939715.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764641","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":"Pre-analytical sample handling standardization for reliable measurement of metabolites and lipids in LC-MS-based clinical research","authors":"A. Sens ,&nbsp;S. Rischke ,&nbsp;L. Hahnefeld ,&nbsp;E. Dorochow ,&nbsp;S.M.G. Schäfer ,&nbsp;D. Thomas ,&nbsp;M. Köhm ,&nbsp;G. Geisslinger ,&nbsp;F. Behrens ,&nbsp;R. Gurke","doi":"10.1016/j.jmsacl.2023.02.002","DOIUrl":"10.1016/j.jmsacl.2023.02.002","url":null,"abstract":"<div><p>The emerging disciplines of lipidomics and metabolomics show great potential for the discovery of diagnostic biomarkers, but appropriate pre-analytical sample-handling procedures are critical because several analytes are prone to <em>ex vivo</em> distortions during sample collection. To test how the intermediate storage temperature and storage period of plasma samples from K3EDTA whole-blood collection tubes affect analyte concentrations, we assessed samples from non-fasting healthy volunteers (n = 9) for a broad spectrum of metabolites, including lipids and lipid mediators, using a well-established LC-MS-based platform. We used a fold change-based approach as a relative measure of analyte stability to evaluate 489 analytes, employing a combination of targeted LC-MS/MS and LC-HRMS screening. The concentrations of many analytes were found to be reliable, often justifying less strict sample handling; however, certain analytes were unstable, supporting the need for meticulous processing. We make four data-driven recommendations for sample-handling protocols with varying degrees of stringency, based on the maximum number of analytes and the feasibility of routine clinical implementation. These protocols also enable the simple evaluation of biomarker candidates based on their analyte-specific vulnerability to <em>ex vivo</em> distortions. In summary, pre-analytical sample handling has a major effect on the suitability of certain metabolites as biomarkers, including several lipids and lipid mediators. Our sample-handling recommendations will increase the reliability and quality of samples when such metabolites are necessary for routine clinical diagnosis.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 35-46"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8c/c4/main.PMC9975683.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10847454","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":"Impact of the loss of laboratory developed mass spectrometry testing at a major academic medical center","authors":"K. Aaron Geno ,&nbsp;Mark A. Cervinski","doi":"10.1016/j.jmsacl.2023.02.005","DOIUrl":"10.1016/j.jmsacl.2023.02.005","url":null,"abstract":"<div><h3>Background</h3><p>Our laboratory historically performed immunosuppressant and definitive opioid testing in-house as laboratory developed (LDT) mass spectrometry-based tests. However, staffing constraints and supply chain challenges associated with the COVID-19 pandemic forced us to refer this testing to a national reference laboratory. The VALID Act could impose onerous requirements for laboratories to develop LDTs. To explore the potential effect of these additional regulatory hurdles, we used the loss of our own LDT tests to assess the impact on patient care and hospital budgets.</p></div><div><h3>Methods</h3><p>Laboratory information systems data and historical data associated with test costs were used to calculate turnaround times and financial impact.</p></div><div><h3>Results</h3><p>Referral testing has extended the reporting of immunosuppressant results by an average of approximately one day and up to two days at the 95th percentile. We estimate that discontinuing in-house opioid testing has cost our health system over half a million dollars in the year since testing was discontinued.</p></div><div><h3>Conclusions</h3><p>Barriers that discourage laboratories from developing in-house testing, particularly in the absence of FDA-cleared alternatives, can be expected to have a detrimental effect on patient care and hospital finances.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 63-66"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d3/0b/main.PMC9938756.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831260","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}