Gas chromatographic-mass fragmentographic determination of propiverine and its metabolites in plasma and urine.

1-Methyl-4-piperidyl diphenylpropoxyacetate hydrochloride has been developed clinically for the therapy of urinary bladder dysfunction. A gas chromatographic-mass fragmentographic method was developed for the determination of this drug and its seven metabolites in plasma and urine. The sample was first treated with a Sep-Pak C18 cartridge, the methanol eluate was evaporated to dryness, and the resulting residue was redissolved in distilled water. This solution was then extracted with chloroform and adjusted to pH 9.0 with 0.1 M sodium borate solution. The acidified aqueous layers were extracted with ethyl acetate. The chloroform layer, which contained non-polar metabolites, was concentrated to dryness, then subjected to trifluoroacetylation, decomposition and methylation. The extract from the plasma sample was trimethylsilylated. The dried residue of the ethyl acetate layer, which contained polar metabolites, was subjected to methylation, trifluoroacetylation and decomposition. Aliquots of each reactant solution were injected into the gas chromatograph-mass spectrometer and analysed by the selected-ion monitoring method using an internal standard. Detection was limited to 1-2 ng/ml of plasma and urine for each metabolite. A precise and sensitive assay for the determination of 1-methyl-4-piperidyl diphenylpropoxyacetate hydrochloride and its metabolites in plasma and urine was thus established, and it should prove useful in basic and clinical pharmacological studies.