Wollein Uwe, Schech Bernd, Hardt Jochen, Schramek Nicholas
Bavarian Health and Food Safety Authority, Veterinärstr. 2, 85764 Oberschleißheim, Germany.
Institute of Laboratory Medicine and Microbiology, Stenglinstr. 2, 86156 Augsburg, Germany.
J Pharm Biomed Anal. 2016 Feb 20;120:100-5. doi: 10.1016/j.jpba.2015.12.006. Epub 2015 Dec 11.
A heavily pregnant woman was treated with Revatio(®) (Sildenafil) against idiopathic pulmonary arterial hypertension, prior to and after her accouchement. To investigate the transfer of sildenafil into breast milk and its metabolism shortly before breastfeeding to the neonatal, a new analytical method was developed and validated, using liquid chromatography tandem mass spectrometry. Additionally, while using linear ion trap scan mode experiments, further metabolites could be identified. Sample preparation was carried out, using solid-phase extraction. For quantification of sildenafil and its major metabolite N-desmethylsildenafil, sildenafil-d8 was used as an internal standard. Within a time frame of 17h covering two Revatio(®) intakes and three breast milk samplings, a concentration range from 1.64 to 4.49ng/ml (sildenafil) and from 1.18 to 1.82ng/ml (N-desmethylsildenafil) could be observed. The current method proved to be accurate and precise in a very low concentration range and establishes the first reported determination of sildenafil and N-desmethylsildenafil in human breast milk.
一名重度孕妇在分娩前后使用瑞伐他汀（西地那非）治疗特发性肺动脉高压。为了研究西地那非在母乳喂养前不久向母乳中的转移及其在新生儿体内的代谢情况，开发并验证了一种使用液相色谱串联质谱的新分析方法。此外，在使用线性离子阱扫描模式实验时，还可以鉴定出更多代谢物。采用固相萃取进行样品制备。为了定量西地那非及其主要代谢物N - 去甲基西地那非，使用西地那非 - d8作为内标。在涵盖两次瑞伐他汀摄入和三次母乳采样的17小时时间范围内，观察到西地那非的浓度范围为1.64至4.49ng/ml，N - 去甲基西地那非的浓度范围为1.18至1.82ng/ml。目前的方法在极低浓度范围内被证明是准确和精确的，并首次报道了人母乳中西地那非和N - 去甲基西地那非的测定。
