title: Determination and quantitation of sildenafil and its major metabolite in the breast milk of a lactating woman.
abstract: 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.
authors.affiliation: Bavarian Health and Food Safety Authority, Veterinärstr. 2, 85764 Oberschleißheim, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Wollein
authors.affiliation: Bavarian Health and Food Safety Authority, Veterinärstr. 2, 85764 Oberschleißheim, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schech
authors.affiliation: Institute of Laboratory Medicine and Microbiology, Stenglinstr. 2, 86156 Augsburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Hardt
authors.affiliation: Bavarian Health and Food Safety Authority, Veterinärstr. 2, 85764 Oberschleißheim, Germany. Electronic address: nicholas.schramek@lgl.bayern.de.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schramek
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D065627:Familial Primary Pulmonary Hypertension / Q000378:metabolism; D005260:Female; D006801:Humans; D007774:Lactation / Q000378:metabolism*; D008895:Milk, Human / Q000737:chemistry*; D011247:Pregnancy; D000068677:Sildenafil Citrate / Q000737:chemistry* / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000068677:Sildenafil Citrate
keywords: Human breast milk; Metabolite screening; Pulmonary arterial hypertension; SPE sample work up; Sildenafil