title: Drug-plasma protein binding assay by electrokinetic chromatography-frontal analysis.
abstract: We developed a rapid, microscale and reliable analytical method for binding of drugs to plasma proteins using capillary electrophoresis (CE) with ionic cyclodextrins (CD) combined with frontal analysis. These CDs were used as pseudostationary phases of electrokinetic chromatography (EKC). The CD-modified EKC (CDEKC) approach allowed us to separate anionic drugs from plasma proteins, whereas CZE could not separate these drugs from plasma proteins because they had a similar mobility like plasma proteins. CDs uniquely interact with these drugs but not with plasma proteins. Therefore, CDEKC could be coupled with frontal analysis to measure the binding of anionic drugs to plasma proteins. The binding values obtained by CDEKC were highly consistent with those determined by the ultrafiltration method. Our CDEKC approach should expand the applicability of CE to protein binding analysis.
authors.affiliation: Analytical Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan. y-ishihama@hhc.eisai.co.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Miwa
authors.forename: Naoki
authors.initials: N
authors.lastname: Asakawa
mesh_terms: D001798:Blood Proteins / Q000737:chemistry*; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods; D003505:Cyclodextrins; D004008:Diclofenac / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D007660:Ketoprofen / Q000737:chemistry*; D004364:Pharmaceutical Preparations; D010653:Phenylbutazone / Q000737:chemistry*; D010672:Phenytoin / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D000077589:Sulfathiazole; D013432:Sulfathiazoles / Q000737:chemistry*; D014859:Warfarin / Q000737:chemistry*; D047392:beta-Cyclodextrins
chemical_list: D001798:Blood Proteins; D003505:Cyclodextrins; D004364:Pharmaceutical Preparations; D012709:Serum Albumin; D013432:Sulfathiazoles; D047392:beta-Cyclodextrins; D004008:Diclofenac; D014859:Warfarin; D010672:Phenytoin; D007660:Ketoprofen; D010653:Phenylbutazone; C031215:betadex; D000077589:Sulfathiazole