Comparison of the Hummel-Dreyer method in high-performance liquid chromatography and capillary electrophoresis conditions for study of the interaction of (RS)-, (R)- and (S)-carvedilol with isolated plasma proteins.
The Hummel-Dreyer method in capillary zone electrophoresis was compared with the corresponding high-performance liquid chromatographic (HPLC) variant in order to study the interaction of racemic carvedilol and its individual enantiomers with isolated human plasma proteins [alpha 1-acid glycoprotein (AGP) and human serum albumin (HSA)]. The binding parameters characterizing the high-affinity binding site of AGP evaluated by using capillary electrophoresis [Ka(RS) = (3.01 +/- 1.15).10(6) l/mol; Ka(S) = (2.13 +/- 0.53).10(6) l/mol; Ka(R) = (4.88 +/- 1.57).10(6) l/mol] were in good accordance with those obtained by HPLC [Ka(RS) = (3.88 +/- 1.74).10(6) l/mol: Ka(S) = (1.80 +/- 0.53) x 10(6) l/mol; Ka(R) = (5.43 +/- 2.53).10(6) l/mol]. Relatively small quantitative differences have been observed considering the attachment of (R)-carvedilol to the secondary low-affinity binding sites on alpha 1-acid glycoprotein by comparing these two methods. In general, the Hummel-Dreyer method applied to capillary zone electrophoresis conditions was verified to be an efficient and fast technique for reliable description of quantitative binding parameters of hydrophobic drugs.
Oravcova
J
J
Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic.
Sojkova
D
D
Lindner
W
W
D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000737:chemistry; D001798:Blood Proteins / Q000378:metabolism*; D002227:Carbazoles / Q000097:blood* / Q000737:chemistry; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D011412:Propanolamines / Q000097:blood* / Q000737:chemistry; D011485:Protein Binding; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000097:blood* / Q000737:chemistry
D000319:Adrenergic beta-Antagonists; D001798:Blood Proteins; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol