Enantioseparation of phenotiazines by affinity electrokinetic chromatography using human serum albumin as chiral selector

Martínez-Gómez, María Amparo; Sagrado, S.; Villanueva-Camañas, R.M.; Medina-Hernández, M.J.

doi:10.1016/j.aca.2006.09.036

Cited by 26 publications

(25 citation statements)

References 21 publications

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“…In order to evaluate the enantioselective binding of drug enantiomers, the affinity EKC (AEKC)-partial filling technique by using HSA as a chiral selector was used. This technique has demonstrated to be useful to chiral resolution of different kind of compounds such as oxprenolol, bupivacaine, propranolol, phenotiazines [9][10][11][12].…”

Section: Introductionmentioning

confidence: 98%

Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE

et al. 2007

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The drug binding to plasma and tissue proteins is a fundamental factor in determining the overall pharmacological activity of a drug. HSA, together with alpha(1)-acid glycoprotein, are the most important plasma proteins, which act as drug carriers, with implications on the pharmacokinetic of drugs. Among plasma proteins, HSA possesses the highest enantioselectivity. In this paper, a new methodology for the study of enantiodifferentiation of chiral drugs with HSA is developed and applied to evaluate the possible enantioselective binding of four antihistamines: brompheniramine, chlorpheniramine, hydroxyzine and orphenadrine to HSA. This study includes the determination of affinity constants of drug enantiomers to HSA and the evaluation of the binding sites of antihistamines on the HSA molecule. The developed methodology includes the ultrafiltration of samples containing HSA and racemic antihistaminic drugs and the analysis of the free or bound drug fraction using the affinity EKC-partial filling technique and HSA as chiral selector. The results shown in this paper represent the first evidence of the enantioselective binding of antihistamines to HSA, the major plasmatic protein.

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Section: Introductionmentioning

confidence: 98%

Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE

et al. 2007

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“…In Table 1 the optimum experimental conditions for the enantioresolution of each compound previously obtained [14][15][16] and the resolution values are shown. Under the optimum conditions, the analytical features for each compound were obtained ( Table 2).…”

Section: Analytical Features Of Drug Enantiomer Determination Using Hmentioning

confidence: 99%

“…The chiral separation of the basic drugs considered using HSA as chiral selector has been performed using the AEKCpartial filling technique [13][14][15]. In Table 1 the optimum experimental conditions for the enantioresolution of each compound previously obtained [14][15][16] and the resolution values are shown.…”

Section: Analytical Features Of Drug Enantiomer Determination Using Hmentioning

confidence: 99%

Evaluation of enantioselective binding of basic drugs to plasma by ACE

et al. 2007

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The present paper deals with the evaluation of the stereoselective binding of antihistamines (brompheniramine, chlorpheniramine, hydroxyzine, orphenadrine and phenindamine), phenothiazines (promethazine and trimeprazine) and a local anesthetic (bupivacaine) to human plasma proteins. Since all of them are drugs highly bound to proteins, a methodology to determine the bound fraction of each drug enantiomer was proposed. This methodology includes the incubation of samples containing plasma and racemic drug, ultrafiltration of the mixture and the chiral separation of enantiomers in the bound drug fraction using affinity EKC (AEKC)-partial filling technique and HSA as chiral selector. The results shown in this paper represent the first evidence of the enantioselective binding of some antihistamines such as brompheniramine, hydroxyzine, orphenadrine and phenindamine and the phenothiazines, promethazine and trimeprazine, to human plasma proteins. The binding of phenindamine to plasma presented the highest enantioselectivity (ES) (ES = 2.5) followed by trimeprazine (ES = 1.5) and promethazine (ES = 1.4).

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“…Because pH is the most critical variable that determines enantioresolution with HSA, experiments in the range of pH 7 -9 were done. For this purpose, the following experimental conditions, selected according to previous experiments [26,27], were fixed: electrophoretic buffer concentration (50 mM Tris), applied voltage (15 kV), temperature (308C), HSA concentration (90 lM) and plug length (180 s) and the effect of running pH (electrophoretic buffer and sample solution) on the enantiomeric resolution was studied. Partial resolution of enantiomers was achieved in the 7.0 -7.5 pH range.…”

Section: Optimization Of Aekc Experimental Conditions For the Enantiomentioning

confidence: 99%

Enantioseparation of nuarimol by affinity electrokinetic chromatography‐partial filling technique using human serum albumin as chiral selector

Martínez-Gómez

Escuder-Gilabert

Villanueva-Camañas

et al. 2008

J of Separation Science

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The present paper deals with the enantiomeric separation of nuarimol enantiomers by affinity EKC-partial filling technique using HSA as chiral selector. Firstly, a study of nuarimol interactions with HSA by CE-frontal analysis was performed. The binding parameters obtained for the first site of interaction were n(1) = 0.84; K(1) = 9.7 +/- 0.3x10(3 )M(-1) and the protein binding percentage of nuarimol at physiological concentration of HSA was 75.2 +/- 0.2%. Due to the moderate affinity of nuarimol towards HSA the possibility of using this protein as chiral selector for the separation of nuarimol using the partial filling technique was evaluated. A multivariate optimization approach of the most critical experimental variables in enantioresolution, running pH, HSA concentration and plug length was carried out. Separation of nuarimol enantiomers was obtained under the following selected conditions: electrophoretic buffer composed of 50 mM Tris at pH 7.3; 160 muM HSA solution applied at 50 mbar for 156 s as chiral selector; nuarimol solutions in the range of 2-8x10(-4) M injected hydrodynamically at 30 mbar for 2 s and the electrophoretic runs performed at 30 degrees C applying 15 kV voltage. Resolution, accuracy, reproducibility speed and cost of the proposed method make it suitable for quality control of the enantiomeric composition of nuarimol in formulations and for further toxicological studies. The results showed a different affinity between nuarimol enantiomers towards HSA.

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Enantioseparation of phenotiazines by affinity electrokinetic chromatography using human serum albumin as chiral selector

Cited by 26 publications

References 21 publications

Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE

Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE

Evaluation of enantioselective binding of basic drugs to plasma by ACE

Enantioseparation of nuarimol by affinity electrokinetic chromatography‐partial filling technique using human serum albumin as chiral selector

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