title: Reverse-phase high-performance liquid chromatography for the simultaneous determination of sildenafil and N-desmethyl sildenafil in plasma of children.
abstract: Sildenafil is a selective inhibitor of cGMP-specific type 5 phosphodiesterase used for the treatment of pulmonary arterial hypertension (PAH) in the adults. In pediatrics, PAH treatment options include the off-label use of sildenafil. Sildenafil is metabolized in the liver by cytocrome P450 into its active metabolite, N-desmethyl sildenafil. The determination of plasma levels of sildenafil and N-desmethyl sildenafil could be useful for therapy optimization and pharmacokinetic studies. We have developed and validated a method for the quantification of sildenafil and its metabolite in plasma of children by rapid extraction, using high-performance liquid chromatography with ultraviolet detection. The calibration range was fitted at least square model (r2≥ 0.999), with an accuracy and an intra- and inter-day relative standard deviation <15% for both analytes. The mean recovery was 102.5% for sildenafil and 101.8% for N-desmethyl sildenafil. This simple method could be successfully used in children with PAH under treatment with sildenafil.
authors.affiliation: Division of Metabolism and Research Unit of metabolic Biochemistry, Children's Hospital and Research Institute 'Bambino Gesù' IRCCS, Viale di San Paolo 15, 00146, Rome, Italy.
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Goffredo
authors.affiliation: Division of Metabolism and Research Unit of metabolic Biochemistry, Children's Hospital and Research Institute 'Bambino Gesù' IRCCS, Viale di San Paolo 15, 00146, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cairoli
authors.affiliation: Division of Metabolism and Research Unit of metabolic Biochemistry, Children's Hospital and Research Institute 'Bambino Gesù' IRCCS, Viale di San Paolo 15, 00146, Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Hospital Pharmacy Unit, Children's Hospital and Research Institute 'Bambino Gesù' IRCCS, Viale di San Paolo 15, 00146, Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Corsetti
authors.affiliation: Laboratory of Metabolomics and Proteomics, Children's Hospital and Research Institute 'Bambino Gesù' IRCCS, Viale di San Paolo 15, 00146, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pastore
mesh_terms: D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D058986:Phosphodiesterase 5 Inhibitors / Q000097:blood*; D015203:Reproducibility of Results; D000068677:Sildenafil Citrate / Q000097:blood*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate
keywords: HPLC; N-desmethyl sildenafil; PAH; sildenafil; stability