A rapid and sensitive LC-MS/MS assay to quantify yonkenafil in rat plasma with application to preclinical pharmacokinetics studies.
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.
Wang
Jiang
J
Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130023, China.
Jiang
Yao
Y
Wang
Yingwu
Y
Tang
Yunbiao
Y
Teng
Guosheng
G
Fawcett
J Paul
JP
Kong
Jian
J
Gu
Jingkai
J
D000085:Acetates / Q000737:chemistry; D000284:Administration, Oral; D000286:Administration, Sublingual; D000818:Animals; D001682:Biological Availability; D002021:Buffers; D002853:Chromatography, Liquid / Q000379:methods*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005215:Fasting; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D011786:Quality Control; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D000085:Acetates; D002021:Buffers; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011744:Pyrimidinones; D011758:Pyrroles; C000613072:yonkenafil; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C018824:ammonium acetate; D000432:Methanol