A rapid and sensitive LC-MS/MS assay to quantify yonkenafil in rat plasma with application to preclinical pharmacokinetics studies

Jiang Wang; Yao Jiang; Yingwu Wang; Yunbiao Tang; Guosheng Teng; J Paul Fawcett; Jian Kong; Jingkai Gu

doi:10.1016/j.jpba.2008.04.004

A rapid and sensitive LC-MS/MS assay to quantify yonkenafil in rat plasma with application to preclinical pharmacokinetics studies

J Pharm Biomed Anal. 2008 Aug 5;47(4-5):985-9. doi: 10.1016/j.jpba.2008.04.004. Epub 2008 Apr 10.

Authors

Jiang Wang¹, Yao Jiang, Yingwu Wang, Yunbiao Tang, Guosheng Teng, J Paul Fawcett, Jian Kong, Jingkai Gu

Affiliation

¹ Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130023, China.

PMID: 18499386
DOI: 10.1016/j.jpba.2008.04.004

Abstract

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.

Publication types

Evaluation Study

MeSH terms

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

Substances

Acetates
Buffers
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Pyrimidinones
Pyrroles
yonkenafil
Cyclic Nucleotide Phosphodiesterases, Type 5
ammonium acetate
Methanol