Nikolaou Panagiota, Papoutsis Ioannis, Athanaselis Sotirios, Pistos Constantinos, Dona Artemis, Spiliopoulou Chara
Department of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece.
Biomed Chromatogr. 2012 Mar;26(3):358-62. doi: 10.1002/bmc.1666. Epub 2011 Jul 1.
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.
丁丙诺啡（BUP）用于维持阿片类药物成瘾孕妇的治疗。由于丁丙诺啡及其主要代谢产物去甲丁丙诺啡会排泄到母乳中，因此已开发、优化并验证了一种灵敏且特异的气相色谱/质谱（GC/MS）方法，用于测定母乳中的这些物质。丁丙诺啡-d4用作内标。样品制备包括蛋白质沉淀与固相萃取及衍生化（乙酰化）相结合。两种分析物的绝对回收率均高于87.3%。检测限和定量限分别为0.07和0.20μg/L。校准曲线在0.20 - 20.0μg/L的动态范围内呈线性，相关系数高于0.996。日内和日间准确度分别在-7.06%至4.50%和-5.88%至7.00%之间，而日内和日间精密度分别小于5.7%和6.1%。发现分析物在母乳中于4℃可稳定保存一周，在-20℃可稳定保存一个月，且经过三次冻融循环后仍稳定。该方法可用于测定接受丁丙诺啡维持治疗的母亲母乳中的丁丙诺啡和去甲丁丙诺啡，以便计算可能通过母乳传递给新生儿的药物量，并避免母乳喂养带来的毒性后果。
