Development and validation of a method for the determination of buprenorphine and norbuprenorphine in breast milk by gas chromatography-mass spectrometry

• Published in: Biomedical chromatography Vol. 26; no. 3; pp. 358 - 362
• Main Authors: Nikolaou, Panagiota, Papoutsis, Ioannis, Athanaselis, Sotirios, Pistos, Constantinos, Dona, Artemis, Spiliopoulou, Chara
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2012
• Subjects: breast milk; buprenorphine; Buprenorphine - analogs & derivatives; Buprenorphine - analysis; Calibration; Gas Chromatography-Mass Spectrometry - methods; GC/MS; Humans; Limit of Detection; Milk, Human - chemistry; nor-buprenorphine; Reference Standards; Reproducibility of Results; Solid Phase Extraction
• ISSN: 0269-3879; 1099-0801
• DOI: 10.1002/bmc.1666

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. Copyright © 2011 John Wiley & Sons, Ltd.