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Am J Perinatol 2021; 38(09): 968-975
DOI: 10.1055/s-0040-1701505
Original Article

Stereoselective Analysis of Methadone and EDDP in Laboring Women and Neonates in Plasma and Dried Blood Spots and Association with Neonatal Abstinence Syndrome

Ingrid F. Metzger‡   *
1   Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana
2   Department of Pharmacy, Faculty of Health Sciences, Universidade de Brasília, Brasília, Brazil
,
Anna E. Thomas‡   *
3   Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
,
Cindy A. Evrard
1   Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana
,
David R. Jones
4   Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
,
Andrea R. Masters
5   Clinical Pharmacology Analytical Core-Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana
,
David M. Haas 
1   Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana
4   Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
,
Laura S. Haneline
3   Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
,
Sara K. Quinney 
1   Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana
4   Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
› Author Affiliations Funding This study was supported by K23 HD071134–01A1 (NICHD) and UL1TR001108 Indiana Clinical and Translational Sciences Institute (Pediatric Project Development Team Funding). Analytical work was performed by the Clinical Pharmacology Analytical Core laboratory, a core laboratory of the Indiana University Melvin and Bren Simon Cancer Center supported by the National Cancer Institute grant P30 CA082709. The funders had no role in the identification, design, conduct, and reporting on this analysis. The content is solely the responsibility of the authors.
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Abstract

Objective This pilot study evaluated the relationship between maternal and neonatal R- and S-methadone and R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) exposure and the severity of neonatal abstinence syndrome (NAS). The use of dried blood spots (DBS) as an alternative for plasma in assessing methadone and EDDP was also assessed.

Study Design Women receiving methadone for medication assisted treatment of opioid use disorder during pregnancy were eligible for recruitment. Plasma and DBS samples were collected from mothers during labor, from cord blood, and from newborns during genetic screen. R-/S-methadone and EDDP were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS). Associations between methadone exposure, neonatal morphine requirements, and severity of NAS were examined.

Results Twenty women and infants completed the study. Maternal methadone dose at delivery was 112 mg/day (range = 60–180 mg/day). Sixteen neonates experienced NAS requiring morphine; three also required phenobarbital. Higher cord blood concentrations of R-methadone, R- and S-EDDP were associated with higher maximum doses of morphine (p < 0.05).

Conclusion Maternal methadone and cord blood concentration at delivery are variable and may be potential markers of neonatal abstinence syndrome.

Keywords

methadone - neonatal abstinence syndrome - opioid use disorder - pharmacokinetics

Note

This work has been presented in part at the American Society for Clinical Pharmacology and Therapeutics 118th Annual Meeting, Washington DC, March 15 to 18, 2017.


* These individuals contributed equally to this work.


Supplementary Material



Publication History

Received: 17 May 2019

Accepted: 31 December 2019

Article published online:
12 February 2020

© 2020. Thieme. All rights reserved.

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