Enantioselective determination of felodipine in human plasma by chiral normal-phase liquid chromatography and electrospray ionisation mass spectrometry.
An analytical method was developed for the determination of the enantiomers of felodipine, a dihydropyridine-type calcium antagonist, in human blood plasma. Felodipine was extracted from plasma using toluene as extraction solvent. The enantiomers were separated on a cellulose tris(4-methyl benzoate) stationary phase (Chiralcel OJ-R) using 2-propanol-iso-hexane (11:89) as mobile phase. Post-column addition of ammonium acetate in ethanol-water (95:5) allowed sensitive detection of the ammonium adduct by electrospray ionisation and selected reaction monitoring. Deuterated felodipine racemate was used as internal standard. Within-run repeatability was determined and a coefficient of variation below 2% was achieved at 22 nmol/l and below 10% at 0.27 nmol/l. Between-day precision was evaluated and a coefficient of variation of 3.6% at 4 nmol/l plasma was obtained. Limit of quantification (LOQ) was set at 0.25 nmol/l (0.10 microg/l). The method proved adequate for pharmacokinetic studies of R- and S-felodipine after oral administration of therapeutic doses of felodipine.
Lindmark
Bo
B
DMPK & Bioanalytical Chemistry, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
Ahnoff
Martin
M
Persson
Bengt-Arne
BA
D002121:Calcium Channel Blockers / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D015736:Felodipine / Q000097:blood* / Q000737:chemistry; D006801:Humans; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D015736:Felodipine