{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T06:40:40Z","timestamp":1778395240935,"version":"3.51.4"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec>\n            <jats:title>Purpose:<\/jats:title>\n            <jats:p>Buprenorphine and methadone are international gold standards for managing opioid use disorders. Although they are efficacious in treating opioid dependence, buprenorphine and methadone present risks, especially during pregnancy, causing neonatal abstinence syndrome and adverse obstetrical outcomes. Buprenorphine and methadone are also abused during pregnancy, and identifying their use is important to limit unprescribed prenatal exposure. Previous studies have suggested that concentrations of buprenorphine, but not methadone markers in unconventional matrices may predict child outcomes, although currently only limited data exist. We reviewed the literature on concentrations of buprenorphine, methadone, and their metabolites in unconventional matrices to improve data interpretation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>A literature search was conducted using scientific databases (PubMed, Scopus, Web of Science, and reports from international institutions) to review published articles on buprenorphine and methadone monitoring during pregnancy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Buprenorphine and methadone and their metabolites were quantified in the meconium, umbilical cord, placenta, and maternal and neonatal hair. Methadone concentrations in the meconium and hair were typically higher than those in other matrices, although the concentrations in the placenta and umbilical cord were more suitable for predicting neonatal outcomes. Buprenorphine concentrations were lower and required sensitive instrumentation, as measuring buprenorphine glucuronidated metabolites is critical to predict neonatal outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Unconventional matrices are good alternatives to conventional ones for monitoring drug exposure during pregnancy. However, data are currently scarce on buprenorphine and methadone during pregnancy to accurately interpret their concentrations. Clinical studies should be conducted with larger cohorts, considering confounding factors such as illicit drug co-exposure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000693","type":"journal-article","created":{"date-parts":[[2019,8,17]],"date-time":"2019-08-17T07:46:49Z","timestamp":1566028009000},"page":"181-193","source":"Crossref","is-referenced-by-count":14,"title":["Monitoring Prenatal Exposure to Buprenorphine and Methadone"],"prefix":"10.1097","volume":"42","author":[{"given":"Annagiulia","family":"Di Trana","sequence":"first","affiliation":[{"name":"Department of Excellence Biomedical Sciences and Public Health, University \u201cPolitecnica delle Marche\u201d of Ancona, Ancona, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nunzia","family":"La Maida","sequence":"additional","affiliation":[{"name":"Department of Excellence Biomedical Sciences and Public Health, University \u201cPolitecnica delle Marche\u201d of Ancona, Ancona, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Tittarelli","sequence":"additional","affiliation":[{"name":"Unit of Forensic Toxicology, Department of Anatomical, Histological, Forensic, and Orthopedic Sciences, Universit\u00e0 la Sapienza, Rome, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilyn A.","family":"Huestis","sequence":"additional","affiliation":[{"name":"Lambert Center for the Study of Medicinal Cannabis and Hemp, Institute of Emerging Health Professions, Thomas Jefferson University, Philadelphia, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Pichini","sequence":"additional","affiliation":[{"name":"National Centre on Addiction and Doping, Istituto Superiore di Sanit\u00e0, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco P.","family":"Busard\u00f2","sequence":"additional","affiliation":[{"name":"Department of Excellence Biomedical Sciences and Public Health, University \u201cPolitecnica delle Marche\u201d of Ancona, Ancona, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Carlier","sequence":"additional","affiliation":[{"name":"Unit of Forensic Toxicology, Department of Anatomical, Histological, Forensic, and Orthopedic Sciences, Universit\u00e0 la Sapienza, Rome, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R6-20230814","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1177\/1535370219851109","article-title":"Placental trophoblast transfer of opioids following exposures to individual or mixtures of opioids in vitro","volume":"244","author":"Mortensen","year":"2019","journal-title":"Exp Biol Med."},{"key":"R7-20230814","doi-asserted-by":"crossref","first-page":"e547","DOI":"10.1542\/peds.2013-3524","article-title":"Neonatal abstinence syndrome","volume":"134","author":"Kocherlakota","year":"2014","journal-title":"Pediatrics"},{"key":"R11-20230814","doi-asserted-by":"crossref","first-page":"742","DOI":"10.3389\/fpsyt.2018.00742","article-title":"Management of opioid addiction with opioid substitution treatments: beyond methadone and buprenorphine","volume":"9","author":"Noble","year":"2019","journal-title":"Front Psychiatry."},{"key":"R13-20230814","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/01.jcp.0000138766.15858.c6","article-title":"Effects of high-dose intravenous buprenorphine in experienced opioid abusers","volume":"24","author":"Umbricht","year":"2004","journal-title":"J Clin Psychopharmacol."},{"key":"R15-20230814","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.clp.2019.02.013","article-title":"Analgesia, opioids, and other drug use during pregnancy and neonatal abstinence syndrome","volume":"46","author":"Jones","year":"2019","journal-title":"Clin Perinatol"},{"key":"R16-20230814","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drugalcdep.2004.11.013","article-title":"Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome","volume":"79","author":"Jones","year":"2005","journal-title":"Drug Alcohol Depend."},{"key":"R17-20230814","doi-asserted-by":"crossref","first-page":"661","DOI":"10.2165\/00003088-200544070-00001","article-title":"Buprenorphine","volume":"44","author":"Elkader","year":"2005","journal-title":"Clin Pharmacokinet."},{"key":"R18-20230814","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/S0024-3205(97)00160-4","article-title":"Involvement of cytochrome P450 3A4 in N-dealkylation of buprenorphine in human liver microsomes","volume":"60","author":"Iribarne","year":"1997","journal-title":"Life Sci."},{"key":"R19-20230814","first-page":"577","article-title":"The metabolism and excretion of buprenorphine in humans","volume":"12","author":"Cone","year":"1984","journal-title":"Drug Metab Disp."},{"key":"R20-20230814","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1373\/clinchem.2008.113712","article-title":"Urinary excretion of buprenorphine, norbuprenorphine, buprenorphine- glucuronide, and norbuprenorphine-glucuronide in pregnant women receiving buprenorphine maintenance treatment","volume":"55","author":"Kacinko","year":"2009","journal-title":"Clin Chem."},{"key":"R21-20230814","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/00007691-199606000-00001","article-title":"Stereoselective pharmacokinetics of methadone in chronic pain patients","volume":"18","author":"Kristensen","year":"1996","journal-title":"Ther Drug Monit."},{"key":"R22-20230814","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s13318-019-00552-0","article-title":"Opioids: a review of pharmacokinetics and pharmacodynamics in neonates, infants, and children","volume":"44","author":"Thigpen","year":"2019","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"R24-20230814","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1089\/cap.2018.0177","article-title":"Developmental consequences of prenatal substance use in children and adolescents","volume":"29","author":"Guille","year":"2019","journal-title":"J Child Adolesc Psychopharmacol."},{"key":"R25-20230814","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1053\/j.semperi.2019.01.003","article-title":"Pharmacological treatment of opioid use disorder in pregnancy","volume":"43","author":"Rodriguez","year":"2019","journal-title":"Semin Perinatol."},{"key":"R26-20230814","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2165\/00003088-200241140-00003","article-title":"Interindividual variability of the clinical pharmacokinetics of methadone","volume":"41","author":"Eap","year":"2002","journal-title":"Clin Pharmacokinet."},{"key":"R27-20230814","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/BF00542102","article-title":"Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method","volume":"20","author":"Meresaar","year":"1981","journal-title":"Eur J Clin Pharmacol."},{"key":"R28-20230814","doi-asserted-by":"crossref","first-page":"35","DOI":"10.5414\/CPP38035","article-title":"Alpha1-acid glycoprotein (AAG) and serum protein binding of methadone in heroin addicts with abstinence syndrome","volume":"38","author":"Garrido","year":"2000","journal-title":"Int J Clin Pharmacol Ther."},{"key":"R29-20230814","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1016\/j.xphs.2018.08.025","article-title":"Methadone metabolism and drug-drug interactions: in vitro and in vivo literature review","volume":"107","author":"Volpe","year":"2018","journal-title":"J Pharm Sci."},{"key":"R30-20230814","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1097\/FTD.0b013e31815c14ce","article-title":"Biological matrices for the evaluation of in utero exposure to drugs of abuse","volume":"29","author":"Lozano","year":"2007","journal-title":"Ther Drug Monit."},{"key":"R31-20230814","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/FTD.0b013e3181d0bd68","article-title":"Maternal buprenorphine dose, placenta buprenorphine and metabolite concentrations and neonatal outcomes","volume":"32","author":"Concheiro","year":"2010","journal-title":"Ther Drug Monit."},{"key":"R32-20230814","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1093\/jat\/34.8.498","article-title":"Umbilical cord monitoring of in utero drug exposure to buprenorphine and correlation with maternal dose and neonatal outcomes","volume":"34","author":"Concheiro","year":"2010","journal-title":"J Anal Toxicol."},{"key":"R33-20230814","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1002\/bmc.3460","article-title":"UHPLC-MS\/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma","volume":"29","author":"Kyle","year":"2015","journal-title":"Biomed Chromatogr."},{"key":"R34-20230814","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.forsciint.2009.04.005","article-title":"Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine-glucuronide and norbuprenorphine-glucuronide in human umbilical cord by liquid chromatography tandem mass spectrometry","volume":"188","author":"Concheiro","year":"2009","journal-title":"Forensic Sci Int."},{"key":"R35-20230814","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0009-9236(97)90053-9","article-title":"Buprenorphine withdrawal syndrome in a newborn","volume":"62","author":"Marquet","year":"1997","journal-title":"Clin Pharmacol Ther."},{"key":"R36-20230814","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1021\/ac701627q","article-title":"Validation and application of a method for the determination of buprenorphine, norbuprenorphine, and their glucuronide conjugates in human meconium","volume":"80","author":"Kacinko","year":"2008","journal-title":"Anal Chem."},{"key":"R37-20230814","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/clpt.2008.156","article-title":"Correlations of maternal buprenorphine dose, buprenorphine, and metabolite concentrations in meconium with neonatal outcomes","volume":"84","author":"Kacinko","year":"2008","journal-title":"Clin Pharmacol Ther."},{"key":"R38-20230814","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1373\/clinchem.2007.091413","article-title":"Buprenorphine and norbuprenorphine in hair of pregnant women and their infants after controlled buprenorphine administration","volume":"53","author":"Goodwin","year":"2007","journal-title":"Clin Chem."},{"key":"R39-20230814","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1111\/j.1365-2125.2010.03759.x","article-title":"(R)- and (S)-methadone and buprenorphine concentration ratios in maternal and umbilical cord plasma following chronic maintenance dosing in pregnancy","volume":"70","author":"Gordon","year":"2010","journal-title":"Br J Clin Pharmacol."},{"key":"R40-20230814","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.clinbiochem.2016.11.026","article-title":"Evaluating a switch from meconium to umbilical cord tissue for newborn drug testing: a retrospective study at an academic medical center","volume":"50","author":"Palmer","year":"2017","journal-title":"Clin Biochem."},{"key":"R41-20230814","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jchromb.2009.11.005","article-title":"Confirmatory analysis of buprenorphine, norbuprenorphine, and glucuronide metabolites in plasma by LCMSMS: application to umbilical cord plasma from buprenorphine-maintained pregnant women","volume":"878","author":"Concheiro","year":"2010","journal-title":"J Chromatogr B Anal Technol Biomed Life Sci."},{"key":"R42-20230814","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.forsciint.2011.10.024","article-title":"Society of Hair Testing guidelines for drug testing in hair","volume":"218","author":"Cooper","year":"2012","journal-title":"Forensic Sci Int."},{"key":"R43-20230814","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/dta.2087","article-title":"Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy","volume":"9","author":"Concheiro","year":"2017","journal-title":"Drug Test Anal."},{"key":"R44-20230814","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1373\/clinchem.2010.154864","article-title":"Maternal methadone dose, placental methadone concentrations, and neonatal outcomes","volume":"57","author":"De Castro","year":"2011","journal-title":"Clin Chem."},{"key":"R45-20230814","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1177\/0890334407300336","article-title":"Concentrations of methadone in breast milk and plasma in the immediate perinatal period","volume":"23","author":"Jansson","year":"2007","journal-title":"J Hum Lact."},{"key":"R46-20230814","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jchromb.2008.04.006","article-title":"Validated method for the simultaneous determination of methadone and its main metabolites (EDDP and EMDP) in plasma of umbilical cord blood by gas chromatography\u2013mass spectrometry","volume":"867","author":"Nikolaou","year":"2008","journal-title":"J Chromatogr B"},{"key":"R47-20230814","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1097\/FTD.0b013e31828a6148","article-title":"Alternative matrices for cocaine, heroin, and methadone in utero drug exposure detection","volume":"35","author":"Concheiro","year":"2013","journal-title":"Ther Drug Monit."},{"key":"R48-20230814","first-page":"112","article-title":"Perinatal effects of combined use of heroin, methadone, and amphetamine during pregnancy and quantitative measurement of metabolites in hair","volume":"53","author":"Su","year":"2012","journal-title":"Pediatrics."},{"key":"R49-20230814","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1097\/FTD.0b013e318288453f","article-title":"Maternal hair analysis for the detection of illicit drugs, medicines, and alcohol exposure during pregnancy","volume":"35","author":"Lendoiro","year":"2013","journal-title":"Ther Drug Monit."},{"key":"R50-20230814","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1093\/jat\/21.2.154","article-title":"Analysis of methadone and its primary metabolite in meconium","volume":"21","author":"Stolk","year":"1997","journal-title":"J Anal Toxicol."},{"key":"R51-20230814","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/jat\/25.1.40","article-title":"Analysis of methadone and its metabolites in meconium by enzyme immunoassay (EMIT\u00ae) and GC-MS","volume":"25","author":"ElSohly","year":"2001","journal-title":"J Anal Toxicol."},{"key":"R52-20230814","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1016\/j.jchromb.2009.07.028","article-title":"Development and validation of a liquid chromatography mass spectrometry assay for the simultaneous quantification of methadone, cocaine, opiates and metabolites in human umbilical cord","volume":"877","author":"de Castro","year":"2009","journal-title":"J Chromatogr B."},{"key":"R53-20230814","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1111\/j.1360-0443.2010.03097.x","article-title":"Prenatal methadone exposure, meconium biomarker concentrations and neonatal abstinence syndrome","volume":"105","author":"Gray","year":"2010","journal-title":"Addiction."},{"key":"R54-20230814","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00216-010-4392-2","article-title":"Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry","volume":"400","author":"Concheiro","year":"2011","journal-title":"Anal Bioanal Chem."},{"key":"R55-20230814","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00216-010-3903-5","article-title":"High-throughput simultaneous analysis of buprenorphine, methadone, cocaine, opiates, nicotine, and metabolites in oral fluid by liquid chromatography tandem mass spectrometry","volume":"398","author":"Concheiro","year":"2010","journal-title":"Anal Bioanal Chem."}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/FTD.0000000000000693","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T22:37:44Z","timestamp":1692052664000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/FTD.0000000000000693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000000693","relation":{},"ISSN":["0163-4356"],"issn-type":[{"value":"0163-4356","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4]]}}}