Meconium nicotine and metabolites by liquid chromatography-tandem mass spectrometry: differentiation of passive and nonexposure and correlation with neonatal outcome measures.

Meconium nicotine and metabolites by liquid chromatography-tandem mass spectrometry: differentiation of passive and nonexposure and correlation with neonatal outcome measures.
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液态色谱串联质谱法的幼虫和代谢产物:被动和无X的分化以及与新生儿结局指标的相关性。

DOI:
10.1373/clinchem.2008.109173
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发表时间:
2008-12
期刊:
影响因子:
9.3
通讯作者:
Huestis MA
Huestis MA
中科院分区:
医学1区
文献类型:
--
作者:
Gray TR;Magri R;Shakleya DM;Huestis MA

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胎粪分析是一种诊断敏感和客观的替代母亲自我报告检测产前烟草暴露。尼古丁和代谢物在胎粪中的分布特征不明确,分析物浓度与新生儿结局的相关性尚未探讨。我们的目的是量化胎粪中的尼古丁、可替宁、反式-3 ′-羟基可替宁(OH-可替宁)、去甲尼古丁、去甲可替宁和葡萄糖醛酸苷浓度,确定子宫内烟草暴露的最佳生物标志物,比较烟草暴露和非暴露新生儿的胎粪浓度,并研究浓度-结局关系。我们用液相色谱-串联质谱法定量测定了暴露于烟草和未暴露于烟草的新生儿胎粪中尼古丁和4种代谢产物的浓度。我们比较了胎粪浓度与出生体重、身长、头围、胎龄以及1分钟和5分钟Apgar评分的关系。尼古丁、可替宁和OH-可替宁是最普遍和最丰富的胎粪烟草生物标志物,在烟草暴露的新生儿中发现浓度较高。而可替宁和OH-可替宁与葡糖苷酸结合,进行冗长且昂贵的酶水解仅鉴别出1份额外的阳性标本。未结合尼古丁、可替宁或OH-可替宁胎粪浓度>10 ng/g最能准确区分主动与被动和非暴露新生儿。定量尼古丁和代谢产物胎粪结果与新生儿结局之间无显著相关性,尽管尼古丁生物标志物的存在预示着头围减小。应在胎粪中分析未结合尼古丁、可替宁和OH-可替宁,以检测子宫内烟草暴露,因为约25%的阳性标本不含可替宁。免疫测定法仅监测可替宁会低估产前烟草暴露的患病率。
Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in meconium is poorly characterized, and correlation of analytes’ concentrations with neonatal outcomes is unexplored. Our objectives were to quantify nicotine, cotinine, trans-3′-hydroxycotinine (OH-cotinine), nornicotine, norcotinine, and glucuronide concentrations in meconium, identify the best biomarkers of in utero tobacco exposure, compare meconium concentrations of tobacco-exposed and nonexposed neonates, and investigate concentration–outcome relationships. We quantified concentrations of nicotine and 4 metabolites with and without hydrolysis simultaneously in meconium from tobacco-exposed and nonexposed neonates by liquid chromatography–tandem mass spectrometry. We compared meconium concentrations to birth weight, length, head circumference, gestational age, and 1- and 5-min Apgar scores. Nicotine, cotinine, and OH-cotinine were the most prevalent and abundant meconium tobacco biomarkers and were found in higher concentrations in tobacco-exposed neonates. Whereas cotinine and OH-cotinine are glucuronide bound, performing the lengthy and costly enzymatic hydrolysis identified only 1 additional positive specimen. Unconjugated nicotine, cotinine, or OH-cotinine meconium concentration >10 ng/g most accurately discriminated active from passive and nonexposed neonates. There was no significant correlation between quantitative nicotine and metabolite meconium results and neonatal outcomes, although presence of a nicotine biomarker predicted decreased head circumference. Unconjugated nicotine, cotinine, and OH-cotinine should be analyzed in meconium to detect in utero tobacco exposure, as approximately 25% of positive specimens did not contain cotinine. Immunoassay testing monitoring cotinine only would underestimate the prevalence of prenatal tobacco exposure.
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