High-performance liquid chromatography-mass spectrometry analysis of diltiazem and 11 of its phase I metabolites in human plasma.
The aim of the present work was to develop a high-performance liquid chromatography-mass spectrometry method for analysis of diltiazem (DTZ) and metabolites in human plasma after single dose administration (120 mg). Human plasma samples (1 ml) were cleaned up by a solid phase extraction procedure (C18 cartridges) using codeine as an internal standard. Reconstituted extracts were separated on a reversed-phase C8 column with a linear gradient mobile phase system. The run time per sample analysis was 11 min. Detection was performed using selected ion monitoring following atmospheric pressure chemical ionization. The lower limit of quantification was estimated to be 1 microg/l (in spiked plasma) for all available reference compounds (i.e. DTZ and five metabolites). Validation of the method showed good linearity, precision and accuracy for quantification of these six reference compounds. In addition, tandem MS analyses of human plasma sampled from healthy individuals after peroral intake of 120 mg DTZ revealed that the method enabled detection of six additional metabolites for which reference compounds were not available.
Molden
Espen
E
Department of Pharmacology, School of Pharmacy, University of Oslo, Oslo, Norway. espen.molden@farmasi.uio.no
Helen Bøe
Grethe
G
Christensen
Hege
H
Reubsaet
Leon
L
D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D003640:Dealkylation; D004110:Diltiazem / Q000097:blood* / Q000493:pharmacokinetics; D005838:Genotype; D006801:Humans; D013058:Mass Spectrometry; D012015:Reference Standards; D015203:Reproducibility of Results
D002121:Calcium Channel Blockers; D019389:Cytochrome P-450 CYP2D6; D004110:Diltiazem