Validation of an LC-ESI-MS/MS method for the quantitation of phosphodiesterase-5 inhibitors and their main metabolites in rat serum and brain tissue samples

► A new LC-ESI-ITMS method is established for the determination of PDE5 inhibitors. ► A sample treatment using HybridSPE-Precipitation cartridges is proposed. ► The method permits the determination of analytes in serum and brain tissue. ► The study has been the first to evaluate the rat brain levels of PDE5 inhibitors.