Determination of dopaminergic prodrugs by high-performance liquid chromatography followed by post-column ion-pair extraction.
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.
Haas
M
M
Department of Pharmacokinetics and Drug Delivery, A. Deusinglaan 1, Groningen, Netherlands.
Moolenaar
F
F
Kluppel
A C
AC
Dijkstra
D
D
Meijer
D K
DK
de Zeeuw
D
D
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
D015259:Dopamine Agents; D011355:Prodrugs