Abstract
Avanafil (AVA) has been FDA approved in 2012 as a phosphodiesterase-type five inhibitor drug (PDE-5), for the treatment of erectile dysfunction (ED). It was necessary to study the pharmacokinetics and bioavailability parameters of AVA since it exhibits side effects, a long time from drug administration. As a result of this, we described a sensitive high-performance-liquid chromatography-triple quad-mass spectrometric method (LC-QqQ-MS) for the analysis of AVA in rat plasma and brain. Furthermore, the concentrations of AVA and its primary metabolites were determined in rat brain since it is known that PDE-5 inhibitor drugs are capable of crossing the blood-brain barrier (BBB). The liquid-liquid extraction method was developed, optimized, and applied for maximum recovery of AVA from plasma and brain homogenates. The percentage of recovery was 96.60 +/- 2.44% and 94.50 +/- 1.86%, in rat plasma and brain homogenate, respectively. The separation was performed on a Nucleodur C18 column, with mobile phase composed of 0.1% formic acid and acetonitrile (29 : 71, v/v), at flow rate 0.5 mL min(-1), and monitored with QqQ-MS applying positive multiple reaction monitoring (MRM) mode. The calculated pharmacokinetic parameters, noncompartmental model, were: C-max 1503.82 +/- 354.11 ng mL(-1) with a t(1/2) value of 4.87 +/- 0.42 h and C-max 141.94 +/- 22.57 ng mL(-1) with a t(1/2) value of 7.05 +/- 1.59 h, for oral AVA suspension and transdermal film, respectively. The average percentage of total metabolites in plasma and brain was 27.1 +/- 2.2% and 7.0 +/- 1.0%, respectively.