Buprenorphine and Norbuprenorphine in Hair of Pregnant Women and Their Infants after Controlled Buprenorphine Administration Robert S. Goodwin, 1 Diana G. Wilkins, 2 Olga Averin, 2 Robin E. Choo, 1,3 Jennifer R. Schroeder, 4 Donald R. Jasinski, 5 Rolley E. Johnson, 6 Hendre ´e E. Jones, 6 and Marilyn A. Huestis 1* Background: Buprenorphine is under investigation as a pharmacotherapeutic agent for treating opioid depen- dence in pregnant women. We hypothesized that there would be a relationship between the cumulative mater- nal dose of buprenorphine during pregnancy and the concentration of buprenorphine and norbuprenorphine in maternal and infant hair. Methods: This study examined buprenorphine and nor- buprenorphine concentrations in hair obtained from 9 buprenorphine-maintained pregnant women and 4 of their infants. Specimens were analyzed by liquid chro- matography-tandem mass spectrometry with limits of quantification of 3.0 pg/mg. All maternal hair specimens were washed with methylene chloride before analysis, and when sufficient amounts of maternal hair were available, specimens also were analyzed without wash- ing. Infant hair specimens were not washed. Results: Buprenorphine concentrations were signifi- cantly greater in unwashed hair than washed hair (P  0.031). Norbuprenorphine concentrations were signifi- cantly greater than buprenorphine concentrations in both maternal (P  0.0097) and infant hair (P  0.0033). There were statistically significant associations between the cumulative maternal dose of buprenorphine admin- istered and the concentrations of buprenorphine (washed, P <0.0001; unwashed, P  0.0004), norbu- prenorphine (washed, P <0.0001; unwashed, P  0.0005), and buprenorphine plus norbuprenorphine (washed, P <0.0001; unwashed, P  0.0005) for both washed and unwashed maternal hair specimens. There was a significant positive association between concen- trations of buprenorphine and norbuprenorphine in maternal hair (washed, P <0.0001; unwashed, P  0.0003), a trend for this association in infant hair (P  0.08), and an association between buprenorphine con- centrations in maternal unwashed hair and infant hair (P  0.0002). The buprenorphine:norbuprenorphine ra- tio increased in distal segments. Conclusion: Buprenorphine treatment during gestation provides an opportunity for monitoring drug disposi- tion in maternal and fetal tissues under controlled conditions. © 2007 American Association for Clinical Chemistry Illicit drugs or alcohol were used by 13% of pregnant women in the US in 1999 and 2000, with opiates account- ing for 19% of the abused substances (1). Buprenorphine, a partial mu opioid agonist and kappa antagonist ap- proved in the US for treatment of nonpregnant opioid- dependent adults, may decrease the incidence and/or severity of neonatal abstinence syndrome often observed after prenatal exposure to full mu agonists (2). Although buprenorphine is not yet approved in the US for use during pregnancy, physicians are prescribing it to preg- 1 Chemistry and Drug Metabolism Section, National Institute on Drug Abuse–Intramural Research Program, National Institutes of Health, Baltimore, MD. 2 Center for Human Toxicology, Department of Pharmacology and Toxi- cology, University of Utah, Salt Lake City, UT. 3 Department of Biology, University of Pittsburgh at Titusville, Titusville, PA. 4 Office of the Clinical Director, National Institute on Drug Abuse– Intramural Research Program, National Institutes of Health, Baltimore, MD. 5 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 6 Reckitt Benckiser Pharmaceuticals, Inc., Richmond, VA. 7 Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bay- view Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD. * Address correspondence to this author at: Chief, Chemistry and Drug Metabolism, National Institute on Drug Abuse–Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Dr., Baltimore, MD 21224. Fax 410-550-2971; e-mail mhuestis@intra.nida.nih.gov. Received May 7, 2007; accepted September 18, 2007. Previously published online at DOI: 10.1373/clinchem.2007.091413 Clinical Chemistry 53:12 000 – 000 (2007) Drug Monitoring and Toxicology 1 http://www.clinchem.org/cgi/doi/10.1373/clinchem.2007.091413 The latest version is at Papers in Press. Published October 5, 2007 as doi:10.1373/clinchem.2007.091413 Copyright (C) 2007 by The American Association for Clinical Chemistry