Reverse‐phase high‐performance liquid chromatography for the simultaneous determination of sildenafil and N‐desmethyl sildenafil in plasma of children

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.