Evaluation of enantioselective binding of basic drugs to plasma by ACE.
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).
Departament de Química Analítica, Facultat de Farmacia, Universitat de Valencia, C/Vicent Andrés Estellés s/n, Valencia, Spain.
María Amparo
MA
Martínez-Gómez
Rosa María
RM
Villanueva-Camañas
Salvador
S
Sagrado
Maria José
MJ
Medina-Hernández
D001798:Blood Proteins / Q000378:metabolism*; D002045:Bupivacaine / Q000378:metabolism*; D019075:Electrophoresis, Capillary / Q000379:methods*; D005069:Evaluation Studies as Topic; D006634:Histamine H1 Antagonists / Q000378:metabolism*; D006801:Humans; D013237:Stereoisomerism; D014462:Ultrafiltration
D001798:Blood Proteins; D006634:Histamine H1 Antagonists; D002045:Bupivacaine