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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: clinchem.2008.109173v1 54/12/2018    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Gray, T. R. Articles by Huestis, M. A. Search for Related Content PubMed PubMed Citation Articles by Gray, T. R. Articles by Huestis, M. A.

Meconium Nicotine and Metabolites by Liquid Chromatography-Tandem Mass Spectrometry: Differentiation of Passive and Nonexposure and Correlation with Neonatal Outcome Measures

¹ Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd., Baltimore, MD; ² Colegio Iberoamericano de Adicciones at Hospital Pereira Rossell, Rbla O’Higgins 4707, Montevideo, Uruguay.

^aAddress correspondence to this author at: 251 Bayview Blvd., Suite 05A721, Baltimore, MD 21224. Fax 443-740-2823; e-mail mhuestis{at}intra.nida.nih.gov

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.