pyrimidinones and ammonium-acetate

A novel method for the quantitation of yonkenafil, a new synthetic phosphodiesterase V inhibitor, in rat plasma using high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) has been developed. The analyte and internal standard (diazepam) were extracted from plasma (100 microl) by liquid-liquid extraction and separated on a C18 column using 10mM ammonium acetate buffer: methanol (15:85, v/v) as mobile phase in a run time of 3.0 min. The detector was a Q-trap mass spectrometer with an ESI interface operating in the multiple reaction monitoring (MRM) mode. The assay was linear over the concentration range 1.0-1000 ng/ml with a limit of detection of 0.20 ng/ml. Intra- and inter-day precision (as relative standard deviation) were both within 8.45% with good accuracy. The method was successfully applied to a preclinical pharmacokinetic study of yonkenafil in rat after sublingual, oral and intravenous administration. The results demonstrate that the sublingual route gives a higher bioavailablity than the oral route and may represent a useful alternative route of yonkenafil administration.

Topics: Acetates; Administration, Oral; Administration, Sublingual; Animals; Biological Availability; Buffers; Chromatography, Liquid; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Evaluation, Preclinical; Drug Stability; Fasting; Hydrogen-Ion Concentration; Injections, Intravenous; Male; Methanol; Molecular Structure; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Pyrimidinones; Pyrroles; Quality Control; Random Allocation; Rats; Rats, Wistar; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Time Factors