title: UHPLC-MS/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma.
abstract: Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC-MS/MS method using solid-phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were <15% for each validated concentration. Our data establishes a 2 week maximum freezer storage window in order to achieve the most accurate cord plasma concentrations of these analytes. Additionally, we found that the umbilical cord tissue analysis was less sensitive compared with analysis with umbilical cord blood plasma, indicating that this may be a more appropriate matrix for determination of buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy.
authors: Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA.
authors: Amy Redmond
authors: AR
authors: Kyle
authors: Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA.
authors: Jennifer
authors: J
authors: Carmical
authors: Department of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors: Darshan
authors: D
authors: Shah
authors: Vanderbilt University Medical Center/Monroe Carell Children's Hospital, Neonatal Perinatal Medicine, Nashville, TN, USA.
authors: Jason
authors: J
authors: Pryor
authors: Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, 37614-1708, USA.
authors: Stacy
authors: S
authors: Brown
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods; D001800:Blood Specimen Collection / Q000379:methods; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D020719:Glucuronides / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D008691:Methadone / Q000097:blood*; D010743:Phospholipids / Q000302:isolation & purification; D011247:Pregnancy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D020719:Glucuronides; D010743:Phospholipids; D002047:Buprenorphine; C043585:norbuprenorphine; D008691:Methadone
keywords: LC-MS/MS; NAS; buprenorphine; methadone