Effect of charged and uncharged chiral additives on the resolution of amlodipine enantiomers in liquid chromatography and capillary electrophoresis

Owens, Paul K.; Fell, Anthony F.; Coleman, Michael W.; Berridge, John C.

doi:10.1016/s0021-9673(97)00995-3

Cited by 41 publications

(25 citation statements)

References 21 publications

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“…So enantioseparation of AL is very important for further studying its pharmacological action and clinic use. At present, Owens et al [12] had separated successfully AL enantiomers in CE using both neutral and anionic CDs.…”

Section: Introductionmentioning

confidence: 99%

Study of interaction between drug enantiomers and human serum albumin by flow injection‐capillary electrophoresis frontal analysis

et al. 2008

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Flow injection (FI)-CE coupled with frontal analysis (FA) was applied to the study of stereoselectivity binding of amlodipine (AL) to HSA. Under protein-drug binding equilibrium, the unbound concentrations of drug enantiomers were measured by plateau height. The stereoselectivity of AL binding to HSA was proved by the different free fractions of two enantiomers. In physiological phosphate solution (pH 7.4, ionic strength 0.17) when 200 microM (+/-)AL was equilibrated with 300 microM HSA, the concentration of unbound R-AL was about 1.5 times higher than that of its antipode. The binding constants of two enantiomers, KR-AL and KS-AL, were 9910-11200 and 90200-104000 M(-1), respectively. The results obtained by the method were compared with those determined by conventional equilibrium dialysis (ED)-CE and fluorescence spectra. Hydroxypropyl-beta-CD (HP-beta-CD) (10 mM) was used as a chiral selector in pH 3.7 phosphate buffer. L-tryptophan (L-try) and ketoprofen (Ket) were used as displacement reagents to investigate the binding sites of AL to HSA. A binding synergism effect between hydrochlorothiazide (QL) and AL was observed and the results suggested that QL can destroy binding equilibrium of R-AL and S-AL toward HSA and they can occupy the same binding site of HSA (site I). The reproducibility was confirmed by RSD (RSD<1.5%) of the plateau height determined by FI-CE frontal analysis (FI-CE-FA). The FI-CE-FA was a good method to study protein-drug interaction.

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Section: Introductionmentioning

confidence: 99%

Study of interaction between drug enantiomers and human serum albumin by flow injection‐capillary electrophoresis frontal analysis

et al. 2008

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“…A stereoselective CE method for amlodipine enantiomers was developed and validated based on published procedures. Thus, Owens et al 15 separated the amlodipine enantio- Fig. 2.…”

Section: Discussionmentioning

confidence: 99%

“…The separation of the enantiomers of amlodipine by capillary electrophoresis has been achieved using uncharged 15,16 and negatively charged cyclodextrin derivatives. 15 Following an initial screening using various neutral and sulfated cyclodextrin derivatives, a-cyclodextrin was selected and a concentration of 18 mM in a 50 mM phosphate buffer, pH 2.5, gave a baseline separation with a resolution of R S 5 2.3.…”

Section: Enantioselective Capillary Electrophoresismentioning

confidence: 99%

“…15 Following an initial screening using various neutral and sulfated cyclodextrin derivatives, a-cyclodextrin was selected and a concentration of 18 mM in a 50 mM phosphate buffer, pH 2.5, gave a baseline separation with a resolution of R S 5 2.3. (S)-Amlodipine (18.7 min) migrated before the (R)-enantiomer (19.4 min) (Fig.…”

Section: Enantioselective Capillary Electrophoresismentioning

confidence: 99%

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Stereoselective plasma protein binding of amlodipine

et al. 2009

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The binding of the (R)- and (S)-enantiomers of amlodipine to bovine serum albumin (BSA), human serum albumin (HSA), alpha(1)-acid glycoprotein (AGP), and human plasma (HP) was studied by equilibrium dialysis over the concentration range of 75-200 microM at a protein concentration of 150 microM. Unbound drug concentrations were determined by enantioselective capillary electrophoresis using 50 mM phosphate buffer, pH 2.5, containing 18 mM alpha-cyclodextrin as background electrolyte. Saturation of the protein binding sites was not observed over the concentration range tested. Upon application of racemic amlodipine besylate, (S)-amlodipine was bound to a higher extend by HSA and HP compared with (R)-amlodipine, whereas the opposite binding of the enantiomers was observed for BSA and AGP. Scatchard analysis was used to illustrate the different binding affinities of amlodipine besylate enantiomers to BSA, HSA and AGP.

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“…In free-solution CE, acidic cyclodextrins (CDs), such as sulfated CDs [17±24], sulfobutyl ether-b-CD [21, 25±28], carboxymethyl- 25,26,28±30], or carboxyethyl-b-CD [21] have been broadly used. Recently, it was also reported on phosphated a-, b-, and g-CDs [31] as chiral BGE additives.…”

Section: Introductionmentioning

confidence: 99%

Development of stereoselective nonaqueous capillary electrophoresis system for the resolution of cationic and amphoteric analytes

Zarbl¹,

Lämmerhofer²,

Franco³

et al. 2001

Electrophoresis

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A stereoselective ion-pair nonaqueous capillary electrophoresis (NACE) method employing the partial filling technique with N-derivatized amino acids, e.g., (R)- and (S)-3,5-dinitrobenzoyl-leucine (DNB-Leu), as chiral selector for the separation of "pseudoenantiomeric" cinchona alkaloid derivatives and other structurally related basic compounds like the enantiomers of mefloquine is presented. Originating from NACE with cinchona alkaloid derivatives as chiral counterions, this method was developed by application of the reciprocity principle of chiral recognition, which was proven to be valid for stereoselective ion-pair capillary electrophoresis (CE). A variety of basic and amphoteric selectands (SAs) could be well resolved. Thereby, the separation was primarily based on stereoselective ion-pair formation of corresponding SA stereoisomers and mobility differences of free and complexed (ion-paired) SAs. Additionally, in the case of diastereomeric SAs, naturally existing mobility differences between the diastereomers played also a role, but was shown by control experiments with racemic DNB-Leu and without selector (SO) to be of minor contribution to overall separation selectivity. Due to its simplicity, speed, and good reproducibility, the established method can be utilized for fast screening of cationic as well as amphoteric chiral compounds, and therefore is a valuable tool in the development of new chiral selectors and chiral stationary phases. Small sample amounts of the SO (4-5 mg) and only analytical amounts of SAs are needed, and about 20-50 compounds per day can be tested.

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Effect of charged and uncharged chiral additives on the resolution of amlodipine enantiomers in liquid chromatography and capillary electrophoresis

Cited by 41 publications

References 21 publications

Study of interaction between drug enantiomers and human serum albumin by flow injection‐capillary electrophoresis frontal analysis

Study of interaction between drug enantiomers and human serum albumin by flow injection‐capillary electrophoresis frontal analysis

Stereoselective plasma protein binding of amlodipine

Development of stereoselective nonaqueous capillary electrophoresis system for the resolution of cationic and amphoteric analytes

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