Clinical Mass Spectrometry最新文献

{"title":"Analysis of urinary VOCs using mass spectrometric methods to diagnose cancer: A review","authors":"Bruno Ruiz Brandão da Costa ,&nbsp;Bruno Spinosa De Martinis","doi":"10.1016/j.clinms.2020.10.004","DOIUrl":"10.1016/j.clinms.2020.10.004","url":null,"abstract":"<div><p>The development of non-invasive screening techniques for early cancer detection is one of the greatest scientific challenges of the 21st century. One promising emerging method is the analysis of volatile organic compounds (VOCs). VOCs are low molecular weight substances generated as final products of cellular metabolism and emitted through a variety of biological matrices, such as breath, blood, saliva and urine. Urine stands out for its non-invasive nature, availability in large volumes, and the high concentration of VOCs in the kidneys. This review provides an overview of the available data on urinary VOCs that have been investigated in cancer-focused clinical studies using mass spectrometric (MS) techniques. A literature search was conducted in ScienceDirect, Pubmed and Web of Science, using the keywords “Urinary VOCs”, “VOCs biomarkers” and “Volatile cancer biomarkers” in combination with the term “Mass spectrometry”. Only studies in English published between January 2011 and May 2020 were selected. The three most evaluated types of cancers in the reviewed studies were lung, breast and prostate, and the most frequently identified urinary VOC biomarkers were hexanal, dimethyl disulfide and phenol; with the latter seeming to be closely related to breast cancer. Additionally, the challenges of analyzing urinary VOCs using MS-based techniques and translation to clinical utility are discussed. The outcome of this review may provide valuable information to future studies regarding cancer urinary VOCs.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.10.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39909497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A proposal for score assignment to characterize biological processes from mass spectral analysis of serum","authors":"Joanna Roder ,&nbsp;Lelia Net ,&nbsp;Carlos Oliveira ,&nbsp;Krista Meyer ,&nbsp;Senait Asmellash ,&nbsp;Sabine Kasimir-Bauer ,&nbsp;Harvey Pass ,&nbsp;Jeffrey Weber ,&nbsp;Heinrich Roder ,&nbsp;Julia Grigorieva","doi":"10.1016/j.clinms.2020.09.001","DOIUrl":"10.1016/j.clinms.2020.09.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Most diseases involve a complex interplay between multiple biological processes at the cellular, tissue, organ, and systemic levels. Clinical tests and biomarkers based on the measurement of a single or few analytes may not be able to capture the complexity of a patient’s disease. Novel approaches for comprehensively assessing biological processes from easily obtained samples could help in the monitoring, treatment, and understanding of many conditions.</p></div><div><h3>Objectives</h3><p>We propose a method of creating scores associated with specific biological processes from mass spectral analysis of serum samples.</p></div><div><h3>Methods</h3><p>A score for a process of interest is created by: (i) identifying mass spectral features associated with the process using set enrichment analysis methods, and (ii) combining these features into a score using a principal component analysis-based approach. We investigate the creation of scores using cohorts of patients with non-small cell lung cancer, melanoma, and ovarian cancer. Since the circulating proteome is amenable to the study of immune responses, which play a critical role in cancer development and progression, we focus on functions related to the host response to disease.</p></div><div><h3>Results</h3><p>We demonstrate the feasibility of generating scores, their reproducibility, and their associations with clinical outcomes. Once the scores are constructed, only 3 µL of serum is required for the assessment of multiple biological functions from the circulating proteome.</p></div><div><h3>Conclusion</h3><p>These mass spectrometry-based scores could be useful for future multivariate biomarker or test development studies for informing treatment, disease monitoring and improving understanding of the roles of various biological functions in multiple disease settings.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39909496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collision energy-breakdown curves – An additional tool to characterize MS/MS methods","authors":"Sophie Mörlein,&nbsp;Carina Schuster,&nbsp;Michael Paal,&nbsp;Michael Vogeser","doi":"10.1016/j.clinms.2020.10.001","DOIUrl":"10.1016/j.clinms.2020.10.001","url":null,"abstract":"<div><h3>Background</h3><p>In tandem mass spectrometry, analyte detection is based on collision-induced fragmentation, which is modulated by the collision energy (CE) setting. Variation in CE leads to differential ion yield, and optimization is usually performed empirically as “tuning” during method development. Our aim was to build a method to objectify the impact of collision energy settings on ion yield for individual compounds.</p></div><div><h3>Methods</h3><p>Collision energy (CE)-breakdown curves were generated based on acquisition files in which a large number of quasi-identical mass transitions were recorded simultaneously, with variation of CE over a defined range within a single injection. Ion yield (normalized to an internal standard recorded with a locked collision energy) was plotted as a curve versus CE settings. Piperacillin and testosterone were studied as exemplary analytes in matrix-free and serum matrix-based liquid chromatography tandem mass spectrometry (LC-MS/MS) measurements. More detailed testosterone CE-breakdown curves were investigated with regard to sample preparation techniques and the isotope labeling pattern of corresponding internal standards.</p></div><div><h3>Results</h3><p>CE-breakdown curves were found characteristically for the piperacillin quantifier transition with respect to CE-related maximum ion yield, as well as curve width and shape. A diverging curve profile was observed for the piperacillin qualifier transition. For testosterone analyses, no impact from different sample preparation techniques or the isotope labeling patterns on the selected CE was shown.</p></div><div><h3>Conclusion</h3><p>CE-breakdown curves are a convenient and valuable tool to verify LC-MS/MS methods regarding consistent fragmentation characteristics between sample sources or native analytes and isotope-labeled counterparts.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.10.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39909499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 liquid chromatography-tandem mass spectrometry method for the simultaneous determination of phthalates and bisphenol a in serum, urine and follicular fluid","authors":"Anna Pia Dima ,&nbsp;Lucia De Santis ,&nbsp;Cristina Verlengia ,&nbsp;Francesco Lombardo ,&nbsp;Andrea Lenzi ,&nbsp;Monica Mazzarino ,&nbsp;Francesco Botrè ,&nbsp;Donatella Paoli ,&nbsp;on behalf of the Italian Society of Embryology, Reproduction, Research (SIERR)","doi":"10.1016/j.clinms.2020.10.002","DOIUrl":"10.1016/j.clinms.2020.10.002","url":null,"abstract":"<div><p>Phthalates and bisphenol A interfere with the synthesis, secretion, transport, binding, metabolism, and excretion of endogenous hormones and, for this reason, are classified as endocrine disruptors.</p><p>We are here presenting an analytical method for the simultaneous detection of six phthalates metabolites and bisphenol A in different biological fluids (urine, serum and follifular fluid) by liquid chromatography coupled to tandem mass spectrometry. The quantification was carried out in negative electrospray ionization mode using selected reaction monitoring as acquisition mode. Different extraction protocols, using either solid phase or liquid/liquid extraction, were comparatively evaluated to optimize the sample preparation procedure. Solid-phase extraction was chosen as it ensured the best recovery and overall sensitivity. The method was successfully validated: recovery varying in the range 71 ± 2%–107 ± 6% depending on the target analyte and the matrix considered, <em>intra-assay</em> and <em>inter-assay precision</em> ≤ 12% for follicular fluid, ≤11% for serum and ≤ 10% for urine and accuracy ≤ 115% for follicular fluid, ≤113% for serum ≤ 115% for urine , linearity with R² &gt; 0.99, with the exception of MEP (recovery 64 ± 8%, <em>intra-assay precision</em> ≤ 20%, <em>inter-assay</em> precision ≤ 16% for follicular fluid). The actual applicability of the method developed and validated in this study was assessed by the analysis of real samples, including 10 specimens of follicular fluid, serum and urine samples, that showed the presence of phthalates metabolites and Bisphenol A, and confirming that the newly developed method can be applied in the routine clinical laboratory for the identification and quantitation of these endocrine-disrupting chemicals.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.10.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39909500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass spectrometry in clinical glycomics: The path from biomarker identification to clinical implementation","authors":"N. de Haan ,&nbsp;M. Wuhrer ,&nbsp;L.R. Ruhaak","doi":"10.1016/j.clinms.2020.08.001","DOIUrl":"10.1016/j.clinms.2020.08.001","url":null,"abstract":"<div><p>Over the past decades, the genome and proteome have been widely explored for biomarker discovery and personalized medicine. However, there is still a large need for improved diagnostics and stratification strategies for a wide range of diseases. Post-translational modification of proteins by glycosylation affects protein structure and function, and glycosylation has been implicated in many prevalent human diseases. Numerous proteins for which the plasma levels are nowadays evaluated in clinical practice are glycoproteins. While the glycosylation of these proteins often changes with disease, their glycosylation status is largely ignored in the clinical setting. Hence, the implementation of glycomic markers in the clinic is still in its infancy. This is for a large part caused by the high complexity of protein glycosylation itself and of the analytical techniques required for their robust quantification. Mass spectrometry-based workflows are particularly suitable for the quantification of glycans and glycoproteins, but still require advances for their transformation from a biomedical research setting to a clinical laboratory. In this review, we describe why and how glycomics is expected to find its role in clinical tests and the status of current mass spectrometry-based methods for clinical glycomics.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39909495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of 17 fentanyls in plasma and blood by UPLC-MS/MS with interpretation of findings in surgical and postmortem casework","authors":"Jonathan P. Danaceau ,&nbsp;Michelle Wood ,&nbsp;Melissa Ehlers ,&nbsp;Thomas G. Rosano","doi":"10.1016/j.clinms.2020.10.003","DOIUrl":"10.1016/j.clinms.2020.10.003","url":null,"abstract":"<div><p>The opioid crisis is linked to an increased misuse of fentanyl as well as fentanyl analogs that originate from the illicit drug market. Much of our current understanding of fentanyl and fentanyl analog use in our communities comes from postmortem toxicology findings. In the clinical settings of addiction medicine and pain management, where the opioid abuse potential is high, the use of fentanyl, as well as specific fentanyl analogs, may be underestimated due to limited plasma testing and limited availability of assays with suitable analytical sensitivity and selectivity to detect misuse of fentanyls. We report plasma and blood assays for 17 fentanyls (these include fentanyl, fentanyl analogs, fentanyl metabolites and synthetic precursors) in clinical, and medical examiner, casework. A mixed-mode solid phase extraction of diluted plasma or precipitated blood was optimized for maximum recovery of the fentanyls with minimized matrix effects. Analysis was performed using a Waters ACQUITY UPLC I-Class interfaced with a Waters Xevo TQ-S micro tandem quadrupole mass spectrometer. Method parameters were optimized and validated for precision, accuracy, carryover, linearity and matrix effects. Application studies were performed in postmortem blood obtained in 44 fentanyl-related fatalities and in serial plasma samples from 18 surgical patients receiving intravenous fentanyl therapy while undergoing parathyroidectomy. Fentanyls found in postmortem cases included fentanyl, norfentanyl, despropionyl-fentanyl (4-ANPP), beta-hydroxy fentanyl (β-OH fentanyl), acetyl fentanyl, acetyl norfentanyl, methoxyacetyl fentanyl, furanyl fentanyl, cyclopropyl fentanyl, and para-fluorobutyryl fentanyl, with fentanyl, norfentanyl, 4-ANPP and β-OH fentanyl predominating in frequency. Fentanyl concentrations ranged from 0.2 to 56 ng/mL and fentanyl was nearly always found with 4-ANPP, norfentanyl and β-OH fentanyl. Concentrations of other fentalogs ranged from &lt;1 to 84 ng/mL (extrapolated). In the surgical cases, fentanyl was detected and quantified along with norfentanyl and β-OH fentanyl, but without detection of 4-ANPP in any of the samples. The association and relative concentrations of β-OH fentanyl, fentanyl and norfentanyl in the postmortem and clinical studies indicated a metabolic, rather than an illicit, source of β-OH fentanyl.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.10.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39909498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Averaging of results derived from different, simultaneously acquired mass transitions in ID-LC-MS/MS – Potential impact on measurement imprecision","authors":"Carina Schuster ,&nbsp;Katharina Habler ,&nbsp;Michael Vogeser","doi":"10.1016/j.clinms.2020.06.001","DOIUrl":"10.1016/j.clinms.2020.06.001","url":null,"abstract":"<div><h3>Background</h3><p>LC–MS/MS allows for many measurands monitoring different mass transitions simultaneously. So far, such alternative mass transitions are usually assessed as “quantifier and qualifier ions” in order to rule out interferences in individual samples. However, quantification can also be based on assessment of alternative mass transitions for both the measurand and its internal standard, with two distinct results for one injection of an individual sample. These paired results can be averaged. The aim of this study was to determine the potential impact of this averaging approach on measurement imprecision.</p></div><div><h3>Methods</h3><p>We studied the impact of averaging results from different transitions for four exemplary measurands (linezolid (LIN), piperacillin (PIP), voriconazole (VOR), ethylglucuronide (ETG)). Intra-batch studies were performed with 21 injections of single clinical samples in sequence for each analyte (LIN, PIP, VOR), and a between-batch study with evaluation of data from routine QC samples from 20 series over 20 weeks (ETG). CVs and their confidence intervals were assessed comparatively for quantification based on single transitions, and for averaged results from these two transitions, respectively.</p></div><div><h3>Results</h3><p>In all data sets, we observed lower CVs for the averaged results compared to the results obtained from single mass transitions. CVs from averaged results were up to 39.4% lower compared to the CVs observed for results obtained from single transitions for the respective measurands.</p></div><div><h3>Conclusion</h3><p>Averaging of quantification results obtained from separate mass transitions acquired simultaneously in ID-LC-MS/MS seems to have the potential to minimize the measurement imprecision for different measurands in short- and long-term settings.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.06.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39909493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of dried blood spot quality control materials for adenosine deaminase severe combined immunodeficiency and an LC-MS/MS method for their characterization","authors":"Brian Young ,&nbsp;Jessica Hendricks ,&nbsp;David Foreman ,&nbsp;C. Austin Pickens ,&nbsp;Candice Hovell ,&nbsp;Víctor R. De Jesús ,&nbsp;Christopher Haynes ,&nbsp;Konstantinos Petritis","doi":"10.1016/j.clinms.2020.07.002","DOIUrl":"10.1016/j.clinms.2020.07.002","url":null,"abstract":"<div><p>Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is an autosomal recessive disorder in which a lack of ADA enzyme prevents the maturation of T- and B-cells; early intervention is crucial for restoring immune function in affected neonates. ADA is responsible for purine metabolism and—in its absence—adenosine, deoxyadenosine, and S-adenosylhomocysteine build up and can be detected in the blood. Preparing dried blood spot (DBS) quality control (QC) materials for these analytes is challenging because enrichments are quickly metabolized by the endogenous ADA in normal donor blood. Adding an inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), has been previously reported to minimize enzyme activity, although this adds additional cost and complexity. We describe an alternative method using unnatural L-enantiomer nucleosides (L-adenosine and L-2′-deoxyadenosine) which eliminates the need for enzyme inhibition. We also present a novel method for characterization of the materials using liquid chromatography mass spectrometry to quantify the analytes of interest.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25587008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct detection of intact Klebsiella pneumoniae carbapenemase variants from cell lysates: Identification, characterization and clinical implications","authors":"William M. McGee ,&nbsp;Matthew L. Faron ,&nbsp;Jason R. Neil ,&nbsp;Scott R. Kronewitter ,&nbsp;Blake W. Buchan ,&nbsp;Nathan A. Ledeboer ,&nbsp;James L. Stephenson Jr.","doi":"10.1016/j.clinms.2020.07.001","DOIUrl":"10.1016/j.clinms.2020.07.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Carbapenemase-producing organisms (CPOs) are a growing threat to human health. Among the enzymes conferring antibiotic resistance produced by these organisms, <em>Klebsiella pneumoniae</em> carbapenemase (KPC) is considered to be a growing global health threat. Reliable and specific detection of this antibiotic resistance-causing enzyme is critical both for effective therapy and to mitigate further spread.</p></div><div><h3>Objectives</h3><p>The objective of this study is to develop an intact protein mass spectrometry-based method for detection and differentiation of clinically-relevant KPC variants directly from bacterial cell lysates. The method should be specific for any variant expressed in multiple bacterial species, limit false positive results and be rapid in nature to directly influence clinical outcomes.</p></div><div><h3>Methods</h3><p>Lysates obtained directly from bacterial colonies were used for intact protein detection using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Bottom-up and top-down proteomic methods were used to characterize the KPC protein targets of interest. Comparisons between KPC-producing and KPC-non-producing isolates from a wide variety of species were also performed.</p></div><div><h3>Results</h3><p>Characterization of the mature KPC protein revealed an unexpected signal peptide cleavage site preceding an AXA signal peptide motif, modifying the molecular weight (MW) of the mature protein. Taking the additional AXA residues into account allowed for direct detection of the intact protein using top-down proteomic methods. Further validation was performed by transforming a KPC-harboring plasmid into a negative control strain, followed by MS detection of the KPC variant from the transformed cell line. Application of this approach to clearly identify clinically-relevant variants among several species is presented for KPC-2, KPC-3, KPC-4 and KPC-5.</p></div><div><h3>Conclusion</h3><p>Direct detection of these enzymes contributes to the understanding of occurrence and spread of these antibiotic-resistant organisms. The ability to detect intact KPC variants via a simple LC-MS/MS approach could have a direct and positive impact on clinical therapy, by providing both direction for epidemiological tracking and appropriate therapy.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39909494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing a method and reference material for quantification of vitamin D binding protein during pregnancy","authors":"Lisa E. Kilpatrick ,&nbsp;Ashley S.P. Boggs ,&nbsp;W. Clay Davis ,&nbsp;Stephen E. Long ,&nbsp;James H. Yen ,&nbsp;Karen W. Phinney","doi":"10.1016/j.clinms.2020.01.002","DOIUrl":"10.1016/j.clinms.2020.01.002","url":null,"abstract":"<div><p>Vitamin D plays a vital role in successful pregnancy outcomes for both the mother and fetus. Vitamin D is bound to vitamin D binding protein (VDBP) in blood and is carried to the liver, kidneys and other target tissues. Accurate measurements of the clinically measured metabolite of vitamin D, 25-hydroxyvitamin D [25(OH)D], depend on complete removal from the binding protein. It has been found that VDBP concentrations increase in maternal serum during pregnancy, obfuscating the accuracy of 25(OH)D concentration measurements in pregnant women. Additionally, measurements of VDBP concentrations during pregnancy have been performed using immunoassays, which suffer from variations due to differences in antibody epitopes, making clinical comparisons difficult. Quantification of VDBP is also of interest because changes in VDBP expression levels may indicate negative outcomes during pregnancy, such as preterm delivery and restricted fetal growth. To address the need for accurate measurement of VDBP during pregnancy, a method using liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) was developed to quantify VDBP using isotopically labeled peptides as internal standards. This method was used to quantify VDBP in Standard Reference Material® (SRM) 1949 Frozen Human Prenatal Serum, which was prepared from separate serum pools of women who were not pregnant and women during each trimester of pregnancy. VDBP concentrations were found to be lowest in the serum pool from non-pregnant women and increased in each trimester. These data had good repeatability and were found to be suitable for reference value assignment of VDBP in SRM 1949.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.01.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}