Differential mobility spectrometry (DMS) reveals the elevation of urinary acetylcarnitine in non‐human primates (NHPs) exposed to radiation

Vera Nicholas B.; Chen Zhidan; Pannkuk Evan; Laiakis Evagelia C.; Fornace Albert J.; Erion Derek M.; Coy Stephen L.; Pfefferkorn Jeffrey A.; Vouros Paul

摘要

Abstract >Acetylcarnitine has been identified as one of several urinary biomarkers indicative of radiation exposure in adult rhesus macaque monkeys (non‐human primates, NHPs). Previous work has demonstrated an up‐regulated dose‐response profile in a balanced male/female NHP cohort.[] As a contribution toward the development of metabolomics‐based radiation biodosimetry in human populations and other applications of acetylcarnitine screening, we have developed a quantitative, high‐throughput method for the analysis of acetylcarnitine. We employed the Sciex SelexIon DMS‐MS/MS QTRAP 5500 platform coupled to flow injection analysis (FIA), thereby allowing for fast analysis times of less than 0.5?minutes per injection with no chromatographic separation. Ethyl acetate is used as a DMS modifier to reduce matrix chemical background. We have measured NHP urinary acetylcarnitine from the male cohorts that were exposed to the following radiation levels: control, 2, 4, 6, 7, and 10?Gy. Biological variability, along with calibration accuracy of the FIA‐DMS‐MS/MS method, indicates LOQ of 20?μM, with observed biological levels on the order of 600?μM and control levels near 10?μM. There is an apparent onset of intensified response in the transition from 6 to 10?Gy. The results demonstrate that FIA‐DMS‐MS/MS is a rapid, quantitative technique that can be utilized for the analysis of urinary biomarker levels for radiation biodosimetry. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><abstract xmlns =“http://www.wiley.com/namespaces/wiley”type =“main”xml：lang =“en”> <title type =“main”>抽象</ title> > acetylcarnitine被鉴定为若干尿生物标志物之一，该尿生物标志物指示成人岩猕猴（非人印象，NHPS）中的辐射暴露。以前的工作已经证明了平衡的男性/雌性NHP队列中的上调剂量 - 反应概况。[]作为对人口群体中基于代谢组织的辐射生物渗透粒子的贡献以及乙酰基氨基筛选的其他应用，我们已经开发了一种定量乙酰氨基分析的高通量方法。我们使用SCIEX Selexion DMS-MS / MS Qtrap 5500平台，耦合到流动注射分析（FIA），从而允许每次注射的快速分析时间小于0.5Ω分钟，没有色谱分离。乙酸乙酯用作DMS改性剂以减少矩阵化学背景。我们从暴露于以下辐射水平的雄性群中测量了NHP尿嘧啶氨基碱：对照，2,4,6,7和10？GY。生物可变性以及FIA-DMS-MS / MS方法的校准精度，表示LOQ为20？μm，观察到的生物水平为600Ωμm，对照水平附近10≤μm。在6到10的过渡中，显然发出了强化响应的响应。结果表明，FIA-DMS-MS / MS是一种快速，定量的技术，可用于分析辐射生物标记水平的泌尿生物标志物水平。</ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-34906/'>《Journal of mass spectrometry: JMS》</a> <b style="margin: 0 2px;">|</b><span>2018年第7期</span><b style="margin: 0 2px;">|</b><span>共12页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Vera Nicholas B.&option=202" target="_blank" rel="nofollow">Vera Nicholas B.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chen Zhidan&option=202" target="_blank" rel="nofollow">Chen Zhidan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Pannkuk Evan&option=202" target="_blank" rel="nofollow">Pannkuk Evan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Laiakis Evagelia C.&option=202" target="_blank" rel="nofollow">Laiakis Evagelia C.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Fornace Albert J.&option=202" target="_blank" rel="nofollow">Fornace Albert J.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Erion Derek M.&option=202" target="_blank" rel="nofollow">Erion Derek M.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Coy Stephen L.&option=202" target="_blank" rel="nofollow">Coy Stephen L.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Pfefferkorn Jeffrey A.&option=202" target="_blank" rel="nofollow">Pfefferkorn Jeffrey A.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Vouros Paul&option=202" target="_blank" rel="nofollow">Vouros Paul;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Pfizer Global Research and DevelopmentCambridge Laboratories Pfizer Inc.Cambridge MA 02139 USA;</p> <p>Department of Chemistry and Chemical BiologyNortheastern University360 Huntington Avenue Boston MA 02115 USA;</p> <p>Georgetown University3700 O Street NW Washington DC 20057 USA;</p> <p>Georgetown University3700 O Street NW Washington DC 20057 USA;</p> <p>Georgetown University3700 O Street NW Washington DC 20057 USA;</p> <p>Pfizer Global Research and DevelopmentCambridge Laboratories Pfizer Inc.Cambridge MA 02139 USA;</p> <p>Department of Chemistry and Chemical BiologyNortheastern University360 Huntington Avenue Boston MA 02115 USA;</p> <p>Pfizer Global Research and DevelopmentCambridge Laboratories Pfizer Inc.Cambridge MA 02139 USA;</p> <p>Department of Chemistry and Chemical BiologyNortheastern University360 Huntington Avenue Boston MA 02115 USA;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1187.html" title="分析化学">分析化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Acetylcarnitine&option=203" rel="nofollow">Acetylcarnitine;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Radiation biodosimetry&option=203" rel="nofollow">Radiation biodosimetry;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Differential mobility spectometry&option=203" rel="nofollow">Differential mobility spectometry;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Separation voltage&option=203" rel="nofollow">Separation voltage;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Compensation voltage&option=203" rel="nofollow">Compensation voltage;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Creatinine&option=203" rel="nofollow">Creatinine;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Flow injection analysis&option=203" rel="nofollow">Flow injection analysis;</a> </p> <div class="translation"> 机译：乙酰氨基碱;辐射生物渗透谱;差动迁移率斑点;分离电压;补偿电压;肌酐;流量注射分析; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" 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