title: Development and validation of a method for the determination of buprenorphine and norbuprenorphine in breast milk by gas chromatography-mass spectrometry.
abstract: Buprenorphine (BUP) is used for the maintenance of opioid-addicted pregnant women. Because BUP and its main metabolite nor-BUP are excreted into breast milk, a sensitive and specific GC/MS method has been developed, optimized and validated for their determination in breast milk. BUP-d4 was used as internal standard. The sample preparation includes combination of protein precipitation with solid-phase extraction and derivatization (acetylation). The absolute recovery for both analytes was found to be higher than 87.3%. The limits of detection and quantification were 0.07 and 0.20 µg/L, respectively. The calibration curves were linear within the dynamic range 0.20-20.0 µg/L, with a correlation coefficient higher than 0.996. Intra- and inter-day accuracies were ranged from -7.06 to 4.50 and from -5.88 to 7.00%, respectively, while intra- and inter-day precision were less than 5.7 and 6.1%. The analytes were found to be stable in breast milk at 4 °C for one week, at -20 °C for one month, and after three freeze-thaw cycles. The method can be used for the determination of BUP and nor-BUP in breast milk of BUP-maintained mothers, in order to calculate the amount of drug that could pass to the newborn via breast milk and to avoid toxic consequences of breastfeeding.
authors: Department of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece. pan_nik@hotmail.com
authors: Panagiota
authors: P
authors: Nikolaou
authors: Ioannis
authors: I
authors: Papoutsis
authors: Sotirios
authors: S
authors: Athanaselis
authors: Constantinos
authors: C
authors: Pistos
authors: Artemis
authors: A
authors: Dona
authors: Chara
authors: C
authors: Spiliopoulou
mesh_terms: D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000032:analysis*; D002138:Calibration; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D008895:Milk, Human / Q000737:chemistry*; D012015:Reference Standards; D015203:Reproducibility of Results; D052616:Solid Phase Extraction
chemical_list: D002047:Buprenorphine; C043585:norbuprenorphine