Determination of Methadone and its Metabolite, 2-Ethylidene-1,5-dimcthyl-3,3-diphenylpyrrolidine (EDDP) in Umbilical Cord Blood

• Published in: Clinical toxicology (Philadelphia, Pa.) Pa.), 2008-06, Vol.46 (5), p.412-412
• Main Authors: Nikolaou, P, Papoutsis, I, Atta-Politou, J, Calokerinos, A, Pistos, C, Spiliopoulou, C, Maravelias, C
• Format: Article
• Language: English
• ISSN: 1556-3650

Objective: The aim of this study was the determination of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in plasma samples obtained from venous and arterial umbilical cord blood, since methadone maintenance is the treatment of choice for rehabilitation of opioid addiction in cases of pregnant women. Significant negative consequences have been reported in methadone-exposed newborns, from which 60-90% develop neonatal abstinence syndrome (NAS), while a constellation of symptoms frequently require prolonged hospitalization and treatment (1). Method: A validated gas chromatogra-phy-mass spectrometric method was used for the determination of methadone and EDDP in plasma samples of venous and arterial umbilical cord blood. The procedure combines protein precipitation and solid phase extraction (2), with minimal matrix effect, leading to absolute recovery of methadone and EDDP higher than 95.6%. This assay uses methadone-d9 as internal standard for the determination of methadone, and EDDP-d3 for the determination of EDDP. Results: This method has been used recently in cases like the one presented in this report Plasma concentrations of methadone of venous and arterial umbilical cord blood samples were 35.7 and 28.7 ng/ml, respectively, while the corresponding concentrations of EDDP were 9.0 and 8.0 ng/ml. The concentrations of methadone and EDDP of the relative plasma sample of the mother were 85.3 and 15.0 ng/ml, respectively. Conclusion: Measuring levels of methadone and its metabolite EDDP in plasma of venous and arterial umbilical cord blood might enlighten the methadone-exposure of infants, whose mothers have been under methadone treatment. Methadone and EDDP concentrations in methadone-maintained pregnancies may affect an altered response in fetal central nervous system and changes in fetal behavior induced by methadone.