BackgroundBuprenorphine is a semi-synthetic opioid used for the treatment of opioid dependence. Opioid use, including buprenorphine, has been increasing in recent years, in the general population and in pregnant women. Consequently, there has been a rise in frequency of neonatal abstinence syndrome (NAS), associated with buprenorphine use during pregnancy. The purpose of this study was to investigate correlations between buprenorphine and buprenorphine-metabolite concentrations in cord blood and onset of NAS in buprenorphine exposed newborns.MethodsNineteen (19) newborns who met inclusion criteria were followed after birth until discharge in a double-blind non-intervention study, after maternal consent. Cord blood and tissue samples were collected and analyzed by liquid chromatography–mass spectrometry (LC–MS) for buprenorphine and metabolites. Simple and multiple logistic regressions were used to examine relationships between buprenorphine and buprenorphine metabolite concentrations in cord blood and onset of NAS, need for morphine therapy, and length of stay.ResultsEach increase in 5 ng/ml level of norbuprenorphine in cord blood increases odds of requiring treatment by morphine 2.5 times. Each increase in 5 ng/ml of buprenorphine-glucuronide decreases odds of receiving morphine by 57.7 %. Along with concentration of buprenorphine metabolites, birth weight and gestational age also play important roles, but not maternal buprenorphine dose.ConclusionsLC–MS analysis of cord blood concentrations of buprenorphine and metabolites is an effective way to examine drug and metabolite levels in the infant at birth. Cord blood concentrations of the active norbuprenorphine metabolite and the inactive buprenorphine-glucuronide metabolite show promise in predicting necessity of treatment of NAS. These finding have implications in improving patient care and reducing healthcare costs if confirmed in a larger sample.

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.