Determination of the Dihydropyridine Aryloxypropanolamine Z6568 and its Acidic Metabolites in Plasma, Urine and Tissues by Solid Phase Extraction and Liquid Chromatography/Negative-ion Mass Spectrometry

Q4 · CHEMISTRY

Article

Author: Pierfrancesco Castelnovo ; Mario Gregori

A sensitive and selective liquid chromatographic/mass spectrometric assay for the determination of the dihydropyridine aryloxypropanolamine compound Z6568 and its monoacidic metabolites in plasma, urine and tissues has been developed and validated. Z6568 and the acidic metabolites were isolated from the biological matrices by solid-phase extraction, separated by reversed-phase high-performance liquid chromatography and detected by mass spectrometry using a thermospray interface. Filament ionization and negative-ion detection were used, monitoring the molecular ion of Z6568 and a major fragment of the acidic metabolites. The analysis of spike plasma, urine and tissues demonstrated good accuracy and precision of the assay with a detection limit of 0.5 ng ml-1 for Z6568 and 2 ng ml-1 for the metabolites. Data relative to the optimization of the extraction procedure, mass spectrometric conditions and the validation protocol are reported. The method was used to investigate the metabolic fate and tissue distribution in laboratory animals.

01 Jan 1996·Journal of Mass SpectrometryQ4 · CHEMISTRY

Determination of the dihydropyridine aryloxypropanolamine compound Z6568 and four metabolites in plasma by liquid chromatography/negative-ion mass spectrometry

Q4 · CHEMISTRY

Article

Author: Pierfrancesco Castelnovo ; Mario Gregori

A sensitive and selective liquid chromatographic/mass spectrometric assay for the determination of the dihydropyridine aryloxypropanolamine compound Z6568 and four metabolites in plasma was developed and validated. Z6568 and the metabolites were isolated from plasma by a simple solvent extraction procedure and separated by reversed-phase high-speed liquid chromatography combined with thermospray mass spectrometry. Filament ionization was used and the molecular negative ions were monitored. The analysis of spiked plasma demonstrated the good accuracy and precision of the assay with a detection limit of 0.5 ng ml-1 for Z6568. Data relative to the optimization of the mass spectrometric conditions and the validation protocol are reported. the method has been used for pharmacokinetic studies in laboratory animals.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Discovery	IT	Zambon Company SpA	-

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