title: Naloxone and Metabolites Quantification in Cord Blood of Prenatally Exposed Newborns and Correlations with Maternal Concentrations.
abstract: ObjectiveTo quantify naloxone and metabolite concentrations in newborns prenatally exposed to sublingual buprenorphine/naloxone and to correlate neonatal and maternal metabolite concentrations.MethodsThis is a prospective observational cohort study. Eleven pregnant women treated for opioid use disorder with sublingual buprenorphine/naloxone were enrolled. Maternal and newborn blood was collected and analyzed for naloxone, buprenorphine, and metabolites via liquid chromatography tandem mass spectrometry. Descriptive statistics and correlation coefficients were utilized to analyze data.ResultsMaternal daily naloxone and buprenorphine doses were 1 to 5 mg and 4 to 20 mg, respectively; the mean (standard deviation) time from medication until delivery was 9.9 (4.3) hours. Naloxone was below the limits of quantification (LOQ) in five infants and six mothers with a range of less than LOQ to 0.3 μg/L. There was a strong positive correlation between maternal and newborn naloxone concentrations: Spearman's ρ = 0.89 (p< 0.01). There were strong positive correlations between maternal and neonatal assays for the buprenorphine analyte concentrations: buprenorphine ρ = 0.88 (p< 0.01), norbuprenorphine ρ = 0.71 (p= 0.01), and norbuprenorphine-glucuronide ρ = 0.98 (p< 0.01), but not for buprenorphine-glucuronide, ρ = 0.53 (p= 0.10).ConclusionNaloxone and buprenorphine are transferred to the fetus during prenatal exposure to maternal sublingual buprenorphine/naloxone. The quantity of naloxone transferred from maternal circulation is minimal and highly correlated with maternal concentrations.
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Wiegand
authors.affiliation: Department of Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse National Institutes of Health, Baltimore, Maryland.
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Swortwood
authors.affiliation: Department of Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse National Institutes of Health, Baltimore, Maryland.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: John
authors.initials: J
authors.lastname: Thorp
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Hendreé E
authors.initials: HE
authors.lastname: Jones
authors.affiliation: Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Neeta L
authors.initials: NL
authors.lastname: Vora
keywords: buprenorphine; naloxone; opioid use disorder; pregnancy