title: Determination of dopaminergic prodrugs by high-performance liquid chromatography followed by post-column ion-pair extraction.
abstract: One possibility to optimize the therapeutic application of dopaminergic compounds with a catechol function is the reversible protection of this moiety using a prodrug approach. Important features in this respect are a proper chemical stability in the gastrointestinal tract, an adequate release rate after arrival in the blood stream or the possibility to cross the blood-brain barrier. A HPLC method was developed to measure the hydrolysis of prodrugs of dopamine and epinine directly. The method is based on reversed-phase separation followed by post-column ion-pair extraction with a fluorescent counter-ion. The separation of di-isobutyryl esters of dopamine and epinine is obtained within 10 min while the more hydrophobic dopaminergic esters, di-benzoyl and di-pivaloyl dopamine, are retained for 30 min. The precision of the assay measuring 160 ng dibudop and 100 ng ibopamine was 1.2 and 1.0%, respectively. The detection limit of all prodrugs tested was approximately 10 ng.
authors.affiliation: Department of Pharmacokinetics and Drug Delivery, A. Deusinglaan 1, Groningen, Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Haas
authors.forename: F
authors.initials: F
authors.lastname: Moolenaar
authors.forename: A C
authors.initials: AC
authors.lastname: Kluppel
authors.forename: D
authors.initials: D
authors.lastname: Dijkstra
authors.forename: D K
authors.initials: DK
authors.lastname: Meijer
authors.forename: D
authors.initials: D
authors.lastname: de Zeeuw
mesh_terms: D002851:Chromatography, High Pressure Liquid; D015259:Dopamine Agents / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D006868:Hydrolysis; D011355:Prodrugs / Q000032:analysis* / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence
chemical_list: D015259:Dopamine Agents; D011355:Prodrugs