title: Methadone and metabolites in hair of methadone-assisted pregnant women and their infants.
abstract: BACKGROUND
  Methadone is the recommended pharmacotherapy for opioid-dependent pregnant women. The primary aims of this study were to determine whether a dose-concentration relationship exists between cumulative maternal methadone dose, methadone and metabolite concentrations in maternal hair during pregnancy and whether maternal hair methadone and metabolite concentrations predict neonatal outcomes.
  
  
  METHODS
  Hair specimens were collected monthly from opioid-dependent mothers enrolled in methadone treatment and 4 of their infants. Hair specimens were segmented (3 cm), washed (maternal hair only), and analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and 2-ethyl-5-methyl-3,3-diphenylpyrroline by liquid chromatography tandem mass spectrometry.
  
  
  RESULTS
  There was large intersubject variability and no dose-concentration relationship for cumulative methadone dose and methadone, EDDP, 2-ethyl-5-methyl-3,3-diphenylpyrroline, or total concentrations in hair. For individual women, a positive trend was noted for cumulative methadone dose and methadone and EDDP concentrations in hair. There was a positive linear trend for cumulative methadone dose and EDDP/methadone ratio in maternal hair, perhaps reflecting methadone's induction of its own metabolism. Maternal methadone concentrations were higher than those in infant hair, and infant EDDP hair concentrations were higher than those in maternal hair. Maternal methadone dose, and methadone and EDDP hair concentrations were not correlated with peak infant neonatal abstinence syndrome (NAS) scores, days to peak NAS, duration of NAS, time to NAS onset, birth length, head circumference, or amount of neonatal morphine pharmacotherapy. Maternal cumulative third trimester methadone dose was positively correlated with infant birth weight.
  
  
  CONCLUSIONS
  Methadone and EDDP in pregnant women's hair are markers of methadone exposure and do not predict total methadone dose, nor neonatal outcomes from in utero methadone exposure.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Himes
authors.forename: Robert S
authors.initials: RS
authors.lastname: Goodwin
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Rock
authors.forename: Hendrée E
authors.initials: HE
authors.lastname: Jones
authors.forename: Rolley E
authors.initials: RE
authors.lastname: Johnson
authors.forename: Diana G
authors.initials: DG
authors.lastname: Wilkins
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006197:Hair / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008691:Methadone / Q000378:metabolism* / Q000627:therapeutic use; D009357:Neonatal Abstinence Syndrome / Q000175:diagnosis / Q000378:metabolism; D058850:Opiate Substitution Treatment / Q000009:adverse effects / Q000379:methods; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D008691:Methadone