ABSTRACT
A simple, fast and sensitive high-performance liquid chromatography (HPLC)-electrospray ionization (ESI) tandem mass spectrometric method (LC-MS/MS) has been developed for determination of propiverine and propiverine N-oxide metabolite in human plasma using oxybutynin as internal standard. Instead of extracting propiverine from plasma using organic solvents, which should be separated from the aqueous phase and evaporated before injecting the sample into the chromatograph, plasma sample containing propiverine and N-oxide was directly injected after precipitating proteins with acetonitrile. Numerous compounds in the plasma did not interfere with the highly specific multiple reaction monitoring in tandem mass spectrometric detection following C(8) reversed-phase chromatographic separation under conditions that eluted propiverine, N-oxide and oxybutynin within 2min (0.1% formic acid in water/acetonitrile, 25:75, v/v). The LC-MS/MS method and an alternative LC-MS method, using methyl-t-butyl ether extraction and selected ion monitoring, were validated over 1-250ngml(-1) of propiverine and 2 to 500ngml(-1) of N-oxide, and successfully applied in a pharmacokinetic study. The lower limit of quantitation was 1ngml(-1) for propiverine and 2ngml(-1) for N-oxide in both methods.
