Liquid chromatographic determination of the adenosine receptor agonist CGS 21680 in blood using on-line solid-phase extraction on a phenylboronic acid support and fluorescence detection.
An analytical method is described for the selective determination of A1 or A2 adenosine receptor agonists in blood. By implementing solid-phase extraction using immobilized-phenylboronic acid (PBA) in sample pretreatment, all adenosine derivatives are retained via their intact cis-diol group. On-line desorption of the analytes from the PBA support to the C18 analytical column is performed by injection of a small plug of perchloric acid. Fluorescence and UV detection are employed for the different adenosine derivatives. The method is applied to the determination of 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N- ethylcarboxyamidoadenosine (CGS 21680, I) in blood using fluorescence detection. The only off-line sample handling step is the extraction of blood with ethyl acetate and subsequent evaporation of the extraction solvent. The detection limit of the method was 0.25 ng (signal-to-noise ratio 3:1) and the determination limit for I in blood (pretreatment of 100 microliters) was 5 ng/ml. The method was validated and used to study the pharmacokinetics of I in rats.
Irth
H
H
Leiden/Amsterdam Center for Drug Research, University of Leiden, Netherlands.
Cleton
A
A
Mathôt
R A
RA
Danhof
M
M
IJzerman
A P
AP
Tjaden
U R
UR
van der Greef
J
J
D000085:Acetates; D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001897:Boronic Acids; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D016903:Drug Monitoring; D006863:Hydrogen-Ion Concentration; D008297:Male; D010627:Phenethylamines / Q000097:blood* / Q000493:pharmacokinetics; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D001897:Boronic Acids; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C007650:ethyl acetate; D000241:Adenosine; C010686:benzeneboronic acid