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.
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.
Gregori
M
M
Medicinal Chemistry Analytical Laboratory, Zambon Group, Bresso (Milan), Italy.
Castelnovo
P
P
D000319:Adrenergic beta-Antagonists / Q000032:analysis* / Q000097:blood / Q000652:urine; D000818:Animals; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000032:analysis* / Q000097:blood / Q000652:urine; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000032:analysis* / Q000097:blood / Q000652:urine; D004285:Dogs; D007536:Isomerism; D013058:Mass Spectrometry; D050198:Phenoxypropanolamines; D051381:Rats; D015203:Reproducibility of Results
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D050198:Phenoxypropanolamines; C101498:Z 6568