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

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How the VALID Act could affect patient access to laboratory developed testing for therapeutic drug monitoring VALID法案如何影响患者获得实验室开发的治疗药物监测测试
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-04-01 DOI: 10.1016/j.jmsacl.2023.02.004
Alec Saitman
{"title":"How the VALID Act could affect patient access to laboratory developed testing for therapeutic drug monitoring","authors":"Alec Saitman","doi":"10.1016/j.jmsacl.2023.02.004","DOIUrl":"10.1016/j.jmsacl.2023.02.004","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":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dc/89/main.PMC9969055.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10824808","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}
引用次数: 1
Bridging the gap: The critical role of laboratory developed tests in clinical toxicology 弥合差距:实验室开发的测试在临床毒理学中的关键作用
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-04-01 DOI: 10.1016/j.jmsacl.2023.02.007
Jaime H. Noguez , Christopher D. Koch
{"title":"Bridging the gap: The critical role of laboratory developed tests in clinical toxicology","authors":"Jaime H. Noguez , Christopher D. Koch","doi":"10.1016/j.jmsacl.2023.02.007","DOIUrl":"10.1016/j.jmsacl.2023.02.007","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":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/06/main.PMC9982682.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10847449","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}
引用次数: 2
Comparison of two highly sensitive benzodiazepine immunoassay lab developed tests for urine drug testing in clinical specimens 比较两种高灵敏度苯二氮卓类药物免疫测定实验室研制的临床尿样药物检测方法
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-04-01 DOI: 10.1016/j.jmsacl.2023.02.010
Kyle Lund , Marlen Menlyadiev , Kyunghoon Lee , Michael J. Kelner , Robert L. Fitzgerald , Raymond T. Suhandynata
{"title":"Comparison of two highly sensitive benzodiazepine immunoassay lab developed tests for urine drug testing in clinical specimens","authors":"Kyle Lund ,&nbsp;Marlen Menlyadiev ,&nbsp;Kyunghoon Lee ,&nbsp;Michael J. Kelner ,&nbsp;Robert L. Fitzgerald ,&nbsp;Raymond T. Suhandynata","doi":"10.1016/j.jmsacl.2023.02.010","DOIUrl":"10.1016/j.jmsacl.2023.02.010","url":null,"abstract":"<div><h3>Background</h3><p>The VALID Act is a legislative effort that, if enacted, would alter the regulatory requirements of laboratory developed tests (LDTs) used for clinical testing in the United States. Benzodiazepines, which are primarily excreted into urine as glucuronidated metabolites such as lorazepam, cross-react poorly with FDA-cleared immunoassays, leading to false-negatives. This shortfall can be addressed with LDTs created by adding glucuronidase to the immunoassay reagents producing “high sensitivity” assays that detect glucuronidated metabolites.</p></div><div><h3>Methods</h3><p>Precision and stability of two high-sensitivity (HS) benzodiazepine immunoassays from Roche and Thermo Scientific were evaluated using manufacturer-supplied quality control (QC) material and glucuronidated QC material. The immunoassays were directly compared to an LC-MS/MS LDT benzodiazepine assay to determine clinical sensitivity/specificity using urine specimens (n = 82 for Thermo Scientific; n = 265 for Roche). The clinical impact of the HS LDT immunoassay was determined by analyzing clinical testing results 60 days before and after its implementation.</p></div><div><h3>Results</h3><p>The precision and clinical sensitivity/specificity of the HS-Thermo Scientific and HS-Roche benzodiazepine assays were acceptable. The reagent stability of the HS-Thermo Scientific immunoassay was poor, whereas the HS-Roche immunoassay was stable. After implementation of the HS-Roche benzodiazepine immunoassay as an LDT, there was a 30-fold increase <em>(p</em>-value: &lt; 0.00001) in the percentage of lorazepam confirmations.</p></div><div><h3>Conclusions</h3><p>We demonstrate the development and validation of an immunoassay LDT with improved sensitivity for glucuronidated benzodiazepines. This LDT can detect glucuronidated benzodiazepines in clinical urine specimens and is stable for 60 days. Importantly, we were able to validate the immunoassay as an LDT by utilizing an LC-MS/MS LDT.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/14/f3/main.PMC10020650.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152995","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}
引用次数: 0
Oxidized LDL is stable in human serum under extended thawed-state conditions ranging from −20 °C to room temperature 氧化LDL在−20°C至室温的延长解冻状态条件下在人血清中是稳定的
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-01-01 DOI: 10.1016/j.jmsacl.2022.12.001
Nilojan Jehanathan , Erandi P. Kapuruge , Stephen P. Rogers , Stacy Williams , Yunro Chung , Chad R. Borges
{"title":"Oxidized LDL is stable in human serum under extended thawed-state conditions ranging from −20 °C to room temperature","authors":"Nilojan Jehanathan ,&nbsp;Erandi P. Kapuruge ,&nbsp;Stephen P. Rogers ,&nbsp;Stacy Williams ,&nbsp;Yunro Chung ,&nbsp;Chad R. Borges","doi":"10.1016/j.jmsacl.2022.12.001","DOIUrl":"10.1016/j.jmsacl.2022.12.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Oxidized LDL (oxLDL) is formed by the spontaneous reaction between aldehyde byproducts of lipid peroxidation and lysine residues of apolipoprotein B within LDL. Clinically, oxLDL is used as a marker of coronary artery disease and predictor of metabolic syndrome risk. Despite its popularity as a clinical marker, no systematic studies of oxLDL stability, in which serum or plasma has been pre-analytically exposed to an array of different time and temperature conditions, have been carried out.</p></div><div><h3>Objective</h3><p>To systematically evaluate the stability of oxLDL in human serum samples exposed to thawed conditions (&gt; −30 °C) for varying periods of time while monitoring a second protein/small molecule redox system as a positive control for non-enzymatic biomolecular activity.</p></div><div><h3>Methods</h3><p>OxLDL was measured in serum samples, from 24 different humans, that had been pre-exposed to three different time courses at 23 °C, 4 °C and −20 °C using ELISA kits from Mercodia that employ the 4E6 mouse monoclonal antibody. A liquid chromatography/mass spectrometry-based marker of serum exposure to thawed conditions known as ΔS-Cys-Albumin was employed as a positive control.</p></div><div><h3>Results</h3><p>OxLDL was stable in serum exposed to 23 °C for up to 48 h, 4 °C for 21 days, or −20 °C for 65 days. ΔS-Cys-Albumin changed dramatically during these time courses (p &lt; 0.001).</p></div><div><h3>Conclusions</h3><p>OxLDL is remarkably stable ex vivo in human serum samples exposed to thawed conditions.</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/ee/d3/main.PMC9791165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10453103","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}
引用次数: 1
A novel fully-automated method to measure steroids in serum by liquid chromatography-tandem mass spectrometry 一种新型全自动液相色谱-串联质谱法测定血清中类固醇的方法
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-01-01 DOI: 10.1016/j.jmsacl.2022.12.004
François Fraissinet , Tony Pereira , Alizée Violin , Guillaume Feugray , Kalyane Bach-Ngohou , Valéry Brunel
{"title":"A novel fully-automated method to measure steroids in serum by liquid chromatography-tandem mass spectrometry","authors":"François Fraissinet ,&nbsp;Tony Pereira ,&nbsp;Alizée Violin ,&nbsp;Guillaume Feugray ,&nbsp;Kalyane Bach-Ngohou ,&nbsp;Valéry Brunel","doi":"10.1016/j.jmsacl.2022.12.004","DOIUrl":"10.1016/j.jmsacl.2022.12.004","url":null,"abstract":"<div><h3>Background</h3><p>Steroids play a key role in numerous physiological processes. Steroid determination is a useful tool to explore various endocrine diseases. Because of its specificity, mass spectrometry is considered to be a reference method for the determination of steroids in serum compared to radioimmunoassay. This technology could progress towards more automation for the optimal organization of clinical laboratories and ultimately for the benefit of patients.</p></div><div><h3>Methods</h3><p>A fully automated ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and fully validated to determine five steroids in serum. Sample preparation was based on protein precipitation with filtration followed by online solid phase extraction. Chromatographic separation was performed using a biphenyl stationary phase.</p></div><div><h3>Results</h3><p>The method was successfully validated according to European Medicine Agency guidelines. Coefficients of variation did not exceed, respectively, 8.4% and 8.1% for intra- and inter-assay precision. Method comparison with radioimmunoassay showed a proportional bias for all compounds, except for testosterone in men. Comparison with another LC-MS/MS method demonstrated acceptable concordance for all steroids, although a small bias was observed for androstenedione.</p></div><div><h3>Conclusion</h3><p>The novelty of this method is that it has been fully automated. Automation provides benefits in traceability and allows significant savings in cost and time.</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/11/a2/main.PMC9804132.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10467921","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}
引用次数: 3
Semi-automated serum steroid profiling with tandem mass spectrometry 串联质谱半自动化血清类固醇分析
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-01-01 DOI: 10.1016/j.jmsacl.2022.12.006
Sophie Rakete, Tom Schubert, Michael Vogeser
{"title":"Semi-automated serum steroid profiling with tandem mass spectrometry","authors":"Sophie Rakete,&nbsp;Tom Schubert,&nbsp;Michael Vogeser","doi":"10.1016/j.jmsacl.2022.12.006","DOIUrl":"10.1016/j.jmsacl.2022.12.006","url":null,"abstract":"<div><h3>Objectives</h3><p>Highly selective and sensitive multi-analyte methods for the analysis of steroids are attractive for the diagnosis of endocrine diseases. Commercially available kits are increasingly used for this purpose. These methods involve laborious solid phase extraction, and the respective panels of target analytes are incomplete. We wanted to investigate whether an improvement of kit solutions is possible by introducing automated on-line solid phase extraction (SPE) and combining originally separate analyte panels.</p></div><div><h3>Methods</h3><p>Sample preparation was performed using automated on-line SPE on a high-pressure stable extraction column. Chromatographic separation, including isobaric compounds, was achieved using a 0.25 mM ammonium fluoride-methanol gradient on a small particle size biphenyl column. Standard compounds and internal standard mixtures of two panels of a commercially available kit were combined to achieve an optimized and straightforward detection of 15 endogenous steroids. Validation was performed according to the European Medicines Agency (EMA) guidelines with slight modifications.</p></div><div><h3>Results</h3><p>Validation was successfully performed for all steroids over a clinically relevant calibration range. Deviations of intra- and inter-assay accuracy and precision results passed the criteria and no relevant matrix effects were detected due to highly effective sample preparation. External quality assessment samples showed the applicability as a routine diagnostic method, which was affirmed by the analyses of anonymized clinical samples.</p></div><div><h3>Conclusions</h3><p>It was found possible to complement a commercially available kit for quantitative serum steroid profiling based on isotope dilution LC-MS/MS by implementing automated on-line SPE, thereby improving the practicality and robustness of the measurement procedure.</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/4f/58/main.PMC9813517.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10513360","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}
引用次数: 3
Identification of a frit-related sample carryover in newborn screening by tandem mass spectrometry 用串联质谱法鉴定新生儿筛查中与水果相关的样品携带
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-01-01 DOI: 10.1016/j.jmsacl.2023.01.001
Kyunghun Kim , Howon Lee , Jeong Joong Lee , Kyoungho Cha , Nam Hyun Park , Young Keun Shin , Hyojin Chae , Eun-Jee Oh
{"title":"Identification of a frit-related sample carryover in newborn screening by tandem mass spectrometry","authors":"Kyunghun Kim ,&nbsp;Howon Lee ,&nbsp;Jeong Joong Lee ,&nbsp;Kyoungho Cha ,&nbsp;Nam Hyun Park ,&nbsp;Young Keun Shin ,&nbsp;Hyojin Chae ,&nbsp;Eun-Jee Oh","doi":"10.1016/j.jmsacl.2023.01.001","DOIUrl":"10.1016/j.jmsacl.2023.01.001","url":null,"abstract":"<div><p>The need for high-throughput analysis of multiple analytes for inborn errors of metabolism in newborn screening (NBS) has led to the introduction of tandem mass spectrometry (MS/MS) into the NBS laboratory. In a flow-injection analysis (FIA), the predominant MS/MS method utilized for NBS, samples are introduced directly into the mass spectrometer without chromatographic separation. When a high-throughput FIA-based MS/MS method is implemented on newer generations of mass spectrometers with increased sensitivity, the risk of carryover and contamination increases. In the present study, we report the carryover of ornithine identified during the implementation of the NeoBase™ 2 (PerkinElmer) non-derivatized kits on the Xevo-TQD platform (Waters Corporation) and describe the source of the carryover, which was traced to the stainless-steel frit-type inline filter. Furthermore, a possible compound-dependent interaction with the stainless-steel frit is suggested based on the structure of ornithine and its effect on separation techniques. Investigation and mitigation of carryover can be a time and resource consuming process, and to this end, our report on identification of a stainless-steel frit as the source of delayed elution and carryover of ornithine should be recognized as a rare, albeit possible source of carryover in FIA-MS/MS methods adopted for NST.</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/e3/ba/main.PMC9850200.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10582105","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}
引用次数: 0
Method validation of multi-element panel in whole blood by inductively coupled plasma mass spectrometry (ICP-MS) 电感耦合等离子体质谱(ICP-MS)测定全血中多元素板的方法验证
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-01-01 DOI: 10.1016/j.jmsacl.2022.12.005
Amol O. Bajaj , Rebecca Parker , Candice Farnsworth , Christian Law , Kamisha L. Johnson-Davis
{"title":"Method validation of multi-element panel in whole blood by inductively coupled plasma mass spectrometry (ICP-MS)","authors":"Amol O. Bajaj ,&nbsp;Rebecca Parker ,&nbsp;Candice Farnsworth ,&nbsp;Christian Law ,&nbsp;Kamisha L. Johnson-Davis","doi":"10.1016/j.jmsacl.2022.12.005","DOIUrl":"10.1016/j.jmsacl.2022.12.005","url":null,"abstract":"<div><h3>Background</h3><p>Analytical methods to measure trace and toxic elements are essential to evaluate exposure and nutritional status. A ten-element panel was developed and validated for clinical testing in whole blood. Retrospective data analysis was conducted on patient samples performed at ARUP Laboratories.</p></div><div><h3>Methods</h3><p>A method was developed and validated to quantify ten elements in whole blood by ICP-MS. Fifty microliters of sample were extracted with 950 μL of diluent containing 1 % ammonium hydroxide, 0.1 % Triton X-100, 1.75 % EDTA along with spiked internal standards. Four calibrators were used for each element and prepared in goat blood to match the patient specimen matrix. Samples were analyzed with an Agilent 7700 ICP-MS with a Cetac MVX 7100 μL Workstation autosampler.</p></div><div><h3>Results</h3><p>The assay was linear for all elements with inter- and intra-assay imprecision less than or equal to 11% CV at the low end of the analytical measurement range (AMR) and less than or equal to 4% CV at the upper end of the AMR for all elements. Accuracy was checked with a minimum of 40 repeat patient samples, proficiency testing samples, and matrix-matched spikes. The linear slopes for the ten elements ranged from 0.94 to 1.03 with intercepts below the AMR and R<sup>2</sup> ranging from 0.97 to 1.00.</p></div><div><h3>Conclusions</h3><p>The multi-element panel was developed to analyze ten elements in whole blood to unify the sample preparation and increase batch run efficiency. The improved analytical method utilized matrix-matched calibrators for accurate quantification to meet regulatory requirements. The assay was validated according to guidelines for CLIA-certified clinical laboratories and was suitable for clinical testing to assess nutritional status and toxic exposure.</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/65/ac/main.PMC9803809.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10467924","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}
引用次数: 4
Validation of a quantitative multiplex LC-MS/MS assay of carvedilol, enalaprilat, and perindoprilat in dried blood spots from heart failure patients and its cross validation with a plasma assay 心衰患者干血斑中卡维地洛、依那普利特和培哚普利特的定量多重LC-MS/MS检测方法的验证及其与血浆检测方法的交叉验证
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-01-01 DOI: 10.1016/j.jmsacl.2022.12.003
Andre Joubert , Anton Joubert , Marthinus van der Merwe , Jennifer Norman , Sandra Castel , Paolo Denti , Karen Sliwa , Gary Maartens , Phumla Sinxadi , Lubbe Wiesner
{"title":"Validation of a quantitative multiplex LC-MS/MS assay of carvedilol, enalaprilat, and perindoprilat in dried blood spots from heart failure patients and its cross validation with a plasma assay","authors":"Andre Joubert ,&nbsp;Anton Joubert ,&nbsp;Marthinus van der Merwe ,&nbsp;Jennifer Norman ,&nbsp;Sandra Castel ,&nbsp;Paolo Denti ,&nbsp;Karen Sliwa ,&nbsp;Gary Maartens ,&nbsp;Phumla Sinxadi ,&nbsp;Lubbe Wiesner","doi":"10.1016/j.jmsacl.2022.12.003","DOIUrl":"10.1016/j.jmsacl.2022.12.003","url":null,"abstract":"<div><h3>Introduction</h3><p>Adherence to medication is an important determinant of outcomes in chronic diseases like heart failure. Drug assays provide objective adherence biomarkers. Dried blood spots (DBS) are appealing samples for drug assays due to less demanding transportation and storage requirements.</p></div><div><h3>Objectives</h3><p>To analytically validate a LC-MS/MS method for the simultaneous quantification of carvedilol, enalaprilat, and perindoprilat in DBS and evaluate the feasibility of using the method as an adherence determining assay. To validate the assay further clinically by establishing correlation and agreement between plasma and DBS samples from a pharmacokinetic pilot study.</p></div><div><h3>Methods</h3><p>The method was validated over a concentration range of 1.00–200 ng/mL according to FDA guidelines. Adherence tracking ability of the assay was evaluated using a pharmacokinetic pilot study. Correlation and agreement were evaluated through Deming regression and Bland-Altman analysis, respectively.</p></div><div><h3>Results</h3><p>Accuracy, precision, selectivity, and sensitivity were proven with complete and reproducible extraction recovery at all concentrations tested. Stability of the analytes in the matrix and throughout sample processing was proven. The full range of concentrations of the pharmacokinetic pilot study could be quantified for enalaprilat, but not for carvedilol and perindoprilat. The difference between the observed and calculated plasma concentrations was less than 20 % of their mean for &gt;67 % of samples for all analytes.</p></div><div><h3>Conclusions</h3><p>The assay is suitable as a screening tool for carvedilol and perindoprilat, while suitable as an adherence determining assay for enalaprilat. Equivalence between observed and predicted plasma concentrations proves DBS and plasma concentrations can be used interchangeably.</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/35/d1/main.PMC9772843.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10803484","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}
引用次数: 0
Effects of sample matrix in the measurement of antithrombin by LC-MS: A role for immunocapture 样品基质对LC-MS测定抗凝血酶的影响:免疫捕获的作用
IF 2.2 4区 医学
Journal of Mass Spectrometry and Advances in the Clinical Lab Pub Date : 2023-01-01 DOI: 10.1016/j.jmsacl.2023.01.002
M. Kruijt , N.P.M. Smit , J.J. van Ham , C.M. Cobbaert , L.R. Ruhaak
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引用次数: 2
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