Novel Assay for Ethylene Glycol Toxicity

乙二醇毒性的新测定方法

• 批准号: 6520105
• 负责人: HANS G KLOEPFER
• 金额: $ 41.33万
• 依托单位: MICRONIX, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6520105
• 关键词: alcohol oxidoreductases; blood chemistry; blood tests; blood toxicology; diagnosis design /evaluation; diagnostic tests; ethylene glycols; glycolates; poisoning; polymers; prognosis; technology /technique development

DESCRIPTION: (Applicant's abstract) Poisoning from ethylene glycol is a potentially lethal medical emergency but can be treated effectively when recognized early. Conversely, when diagnosis is late, the outcome is usually poor. The major pathogenic factor is metabolic acidosis from glycolic acid (glycolate). Because laboratory testing for ethylene glycol and glycolate is severely restricted, timely diagnosis depends on comparatively nonspecific physical signs and laboratory tests. Lack of access to specific testing and need for differentiation from conditions featuring similar symptoms constitute a unique medical dilemma. Recognizing these deficiencies we propose to develop novel, specific enzymic assays for ethylene glycol and glycolate. Two product configurations are perceived: 1) aqueous reagents for existing clinical analyzers (serum, quantitative); 2) a dry-chemistry, dual-analyte point-of-care testrip method (whole blood, semi-quantitative).The POC method is a dual-analyte test tab device for the simultaneous estimation of ethylene glycol and glycolate from approximately two (2) microliters of whole blood without centrifugation or any other form of sample or reagent handling. To make such a level of miniaturization and simplicity feasible, we have developed a capillary fill sampling technique permitting specimen dosing, plasma separation, and red cell removal in one wholly integrated step. Because of rapid metabolism of (flontoxic) ethylene glycol and the longer half life of (toxic) glycolate, the latter provides better prognostic information and improved clinical sensitivity, especially late post-ingestion. Thus, rapid and simultaneous availability of test results for both analytes expands the window of diagnostic/therapeutic opportunity. Socioeconomic benefits are: 1) reducing expensive gas chromatographic screening, confirmatory and other testing; 2) averting late or unnecessary treatment; 3) cutting intensive care and hospital stay; 4) abating long term morbidity (renal dialysis). PROPOSED COMMERCIAL APPLICATION: Most current gas chromatographic screening and confirmatory methods for ethylene glycol require derivatization, sample pretreatment and special columns. Direct methods are fraught with analytical problems such as peak overlap and trailing. Cases have been reported where other compounds were identified as ethylene glycol with serious consequences. All methods require specialized equipment unavailable in most laboratories, are technically demanding, time consuming, and relatively insensitive. For these reasons access to timely and reliable testing for ethylene glycol is extremely limited. Testing for the clinically more sensitive and relevant toxic metabolite glycolic acid is essentially non-existant. Not a single routine clinical analyzer currently exists offering either an ethylene glycol or glycolate method. The proposed products would solve these problems.

描述：（申请人摘要）乙二醇中毒是一种 可能致命的医疗紧急情况，但在以下情况下可以得到有效治疗： 很早就认识了。相反，当诊断较晚时，结果通常是 贫穷的。主要致病因素是乙醇酸代谢性酸中毒 （乙醇酸盐）。因为乙二醇和乙醇酸酯的实验室测试是 严重受限，及时诊断依赖于相对非特异性 体征和实验室测试。 缺乏特定测试的机会，需要根据具体情况进行区分 具有相似的症状构成了独特的医学困境。认识 针对这些缺陷，我们建议开发新颖的、特异性的酶检测方法 乙二醇和乙醇酸酯。感知到两种产品配置：1) 现有临床分析仪（血清、定量）的水性试剂； 2）一个 干化学、双分析物即时测试条法（全血、 POC 方法是一种双分析物测试片装​​置，用于 从大约两个中同时估计乙二醇和乙醇酸酯 (2) 未经离心或任何其他形式的微升全血 样品或试剂处理。为了实现如此程度的小型化和 简单可行，我们开发了毛细管填充采样技术 允许样品加样、血浆分离和红细胞去除于一体 完全集成的步骤。由于（氟龙毒性）乙烯的快速代谢 乙二醇和（有毒）乙醇酸盐的较长半衰期，后者提供 更好的预后信息和提高的临床敏感性，特别是 摄入后晚期。因此，可以快速、同时获得测试结果 两种分析物都扩大了诊断/治疗机会的窗口。 社会经济效益是：1）减少昂贵的气相色谱分析 筛选、确认和其他测试； 2）避免迟到或不必要的 治疗; 3）减少重症监护和住院时间； 4）长期减弱 发病率（肾透析）。 拟议的商业应用： 最新乙二醇气相色谱筛选和验证方法 需要衍生化、样品预处理和特殊色谱柱。 直接方法充满了麻烦 分析问题，例如峰重叠和拖尾。 已报告病例的地点 其他化合物被鉴定为乙二醇，造成严重后果。 所有方法 需要大多数实验室无法提供的专业设备，技术要求高， 耗时且相对不敏感。 由于这些原因，可以及时、可靠地获取 乙二醇的测试极其有限。 测试临床上更敏感和 相关的有毒代谢物乙醇酸基本上不存在。 没有一个常规的临床 目前存在提供乙二醇或乙醇酸盐方法的分析仪。 这 所提出的产品将解决这些问题。