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通过对脐带进行靶向和非靶向代谢组学分析,筛查胎儿期暴露的阿片类药物和兴奋剂。

Screening for Opioid and Stimulant Exposure In Utero Through Targeted and Untargeted Metabolomics Analysis of Umbilical Cords.

机构信息

Department of Chemistry, Thomas Harriot College of Arts and Sciences, East Carolina University.

Department of Pediatrics, Brody School of Medicine at East Carolina University.

出版信息

Ther Drug Monit. 2020 Oct;42(5):787-794. doi: 10.1097/FTD.0000000000000753.

DOI:10.1097/FTD.0000000000000753
PMID:32142018
Abstract

BACKGROUND

Neonatal abstinence syndrome is an array of signs and symptoms experienced by a newborn due to abrupt discontinuation of intrauterine exposure to certain drugs, primarily opioids. In the United States, the incidence of neonatal abstinence syndrome has tripled over the past decade. The current standard of care for drug testing includes the analysis of infant urine and meconium. Sample collection is associated with several limitations, including diaper media interferences, limited sample amount, sample heterogeneity, and the need for professional staff for collection. Umbilical cord tissue has emerged as a convenient sample matrix for testing owing to its universal availability. The purpose of this study was to examine umbilical cords using an untargeted metabolomics approach to determine the detected drugs and validate an analytical method to confirm and quantify the identified drugs.

METHODS

A metabolomics analysis was performed with 21 umbilical cords to screen for drugs and drug metabolites by liquid chromatography-mass spectrometry. Drugs were identified using the National Institute of Standards and Technology database, and an analytical method was developed and validated using secondary liquid chromatography-mass spectrometry instrument for positive confirmation and quantitative analysis.

RESULTS

Twenty-one random umbilical cords from women were tested: 4 were positive for cocaine and the primary and secondary metabolites; one was positive for methadone, the primary metabolite; 3 were positive for cotinine, the metabolite of nicotine; and 5 were positive for acetyl norfentanyl.

CONCLUSIONS

Our research is a prospective method development study using untargeted and targeted approaches to characterize steady-state drug metabolite levels in the umbilical cord matrix at the time of delivery. By characterizing drug type and concentration, this methodology can be used to develop a reliable complementary testing method for meconium toxicology screens.

摘要

背景

新生儿戒断综合征是指新生儿因宫内暴露于某些药物(主要是阿片类药物)而突然中断而出现的一系列体征和症状。在美国,新生儿戒断综合征的发病率在过去十年中增加了两倍。目前,药物检测的标准护理包括婴儿尿液和胎粪分析。样本采集存在多种局限性,包括尿布介质干扰、样本量有限、样本异质性以及对采集专业人员的需求。由于脐带组织普遍存在,因此它已成为一种用于测试的方便样本基质。本研究旨在使用非靶向代谢组学方法检查脐带,以确定检测到的药物,并验证一种分析方法来确认和定量鉴定的药物。

方法

对 21 根脐带进行代谢组学分析,通过液相色谱-质谱法筛选药物和药物代谢物。使用国家标准与技术研究所数据库鉴定药物,并使用二级液相色谱-质谱仪开发和验证分析方法,以进行阳性确认和定量分析。

结果

对 21 名女性的随机脐带进行了测试:4 根对可卡因及其主要和次要代谢物呈阳性;1 根对美沙酮及其主要代谢物呈阳性;3 根对可替宁(尼古丁的代谢物)呈阳性;5 根对乙酰去甲芬太尼呈阳性。

结论

我们的研究是一项使用非靶向和靶向方法的前瞻性方法开发研究,旨在描述分娩时脐带基质中稳态药物代谢物水平。通过描述药物类型和浓度,该方法可用于开发可靠的补充胎粪毒理学筛选测试方法。

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