Determination and quantitation of sildenafil and its major metabolite in the breast milk of a lactating woman

• A novel LC–MS-based assay of sildenafil and its major metabolite from human breast milk was developed and validated.
• A concentration range of sildenafil in human breast milk was determined and discussed.
• MS/MS experiments on further sildenafil metabolites in human breast milk were conducted.

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 17 h covering two Revatio® intakes and three breast milk samplings, a concentration range from 1.64 to 4.49 ng/ml (sildenafil) and from 1.18 to 1.82 ng/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.

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