Determination of felodipine enantiomers using chiral stationary phase liquid chromatography and gas chromatography/mass spectrometry, and the study of their pharmacokinetic profiles in human and dog

Abstract

A stereoselective and sensitive method for the determination of the enantiomers of felodipine, a dihydropyridine calcium antagonist, has been developed and the pharmacokinetic profiles of the enantiomers comparatively studied after oral administration to dogs and humans. D6-Felodipine, the internal standard, was added to the plasma, extracted with a solvent and then optically resolved into S(-) and R(+) enantiomers on a high performance liquid chromatographic Chiralcel OJ column. Each enantiomer in the effluent was analysed by capillary column gas chromatography/positive ion electron impact mass spectrometry. After oral administration of the felodipine racemate, the Tmax and t1/2 values hardly differed between the two enantiomers in dogs and humans. The Cmax and AUC0-24 h values of the S(-) enantiomer were slightly higher than those of the R(+) enantiomer in humans but the difference between the enantiomers was not significant. These results suggested that there is no large difference in the absorption, distribution and elimination of felodipine enantiomers after oral administration of the racemate in either dog or human.

Enantiomeric Recognition of Racemic 4‐Aryl‐1,4‐dihydropyridine Derivatives via Chiralpak AD‐H Stationary Phases

“…For example, dihydropyridine separations by polysaccharide type CSPs predominate. Cellulose tris(4‐methylbenzoate) coated on silica gel (Chiralcel OJ) and Chiralpak AD, consisting of amylose tris(3,5‐dimethylphenylcarbamate), have often been used for dihydropyridine resolutions. OA‐4500, AGP, and ES‐OVM CSPs have also been employed.…”

Gas-Phase Chiral Differentiation of Amino Acid Guests in Cyclodextrin Hosts

“…Currently, cyclodextrins are used in conjunction with HPLC to separate and quantify enantiomeric mixtures of amino acids. The interaction of amino acids and cyclodextrins produces a host−guest complex that can be chromatographically separated. − Several examples of chiral recognition in mass spectrometry have been reported. − The majority of these studies takes advantage of the excess energy produced during ionization to differentiate enantiomers. For example, the population of complexes formed with FAB have a high metastable component.…”

Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

“…Differences between species are also common; for example, the metabolic oxidation of felodipine in humans is greater for the ( S )-enantiomer, whereas rats and dogs preferentially metabolize the ( R )-enantiomer [ 47 ].…”