Chiral separation of the β₂‐sympathomimetic fenoterol by HPLC and capillary zone electrophoresis for pharmacokinetic studies

Abstract

The development of methods for the separation of the enantiomers of fenoterol by chiral HPLC and capillary zone electrophoresis (CZE) is described. For the HPLC separation precolumn fluorescence derivatization with naphthyl isocyanate was applied. The resulting urea derivatives were resolved on a cellulose tris(3,5-dimethylphenylcarbamate)-coated silica gel column employing a column switching procedure. Detection was carried out fluorimetrically with a detection limit in the low ng/mL range. The method was adapted to the determination of fenoterol enantiomers in rat heart perfusates using liquid-liquid extraction. As an alternative a CE method was used for the direct separation of fenoterol enantiomers comparing different cyclodextrin derivatives as chiral selectors.

Development and validation of a sensitive LC–MS/MS method for the determination of fenoterol in human plasma and urine samples

“…The (R,R′)- and (S,S′)-Fen enantiomers were resolved with an α = 1.09 and R s = 1.4, similar to or slightly improved from previously reported methods [3,19], where α = 1.21 and R s = 1.06 [3] and α = 1.19 and R s = 2.0 [19] were obtained. The current method differed from previously reported methods having (R,R′)-Fen eluting first (figure 2a).…”

“…Enantioselective separations of (R,R′)-Fen and (S,S′)-Fen have been reported using an amylose tris (3,5-dimethylphenylcarbamate) (Chiralpack AD) LC column [18], capillary zone electrophoresis [19], an CE separations using cyclodextrin derivatives [20–22] and α-glycoprotein [23]. These methods all lacked sufficient sensitivity for our assays and in some cases also required extensive workup.…”

Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis

“…Concerning biodegradation and environmental fate, the recognition of enantioselectivity is essential to provide a more realistic risk assessment of chiral compounds [79]. Several different technologies have been reported for the enantioseparation of β 2 -agonists enantiomers, including predominantly liquid chromatography (LC, HPLC) using chiral stationary phase (CSP) [80] or derivatizing reagents [81] as well as GC, TLC, and capillary electrophoresis (CE) using cyclodextrins or their derivatives as chiral selectors [63,82].…”

“…Generally, chiral separation can be carried out by (a) direct separation of the enantiomers using CSPs or chiral mobile additives or (b) indirect separation by conversion of the enantiomers to diastereoisomers using a chiral reagent followed by chromatography on a chiral column [82,83]. Direct chromatographic enantioseparation on CSP has appeared as the most effective and convenient way of determining the enantiomeric composition of chiral drugs.…”

“…Detection was carried out fluorometrically with a detection limit in the low nanograms per milliliter. The method was adapted to the determination of fenoterol enantiomers in hat heart perfusates [82].…”