AICA-riboside: direct quantitation in ultrafiltrates of plasma by HPLC during pharmacokinetic studies in man.
A simple HPLC procedure for the quantitation of AICA-riboside (Z) and its 5-monophosphate metabolite (ZMP) in ultrafiltrates of plasma and lysed whole blood, respectively, has been developed. Samples of plasma or previously frozen whole blood were subjected to ultrafiltration by centrifuging for 30 minutes in an Amicon Centrifree Micropartition cartridge and the filtrates analyzed directly by HPLC. Compound Z was quantitated by UV detection at 270 nm following isocratic reverse-phase chromatography on a C18 column and ZMP following isocratic chromatography on an anion exchange (SAX) column. The limits of sensitivity for Z in plasma and ZMP in blood were 0.1 and 2.5 micrograms/ml, respectively. Neither compound was protein bound and recoveries were greater than 95%. The intra- and inter-day coefficients of variation were less than 5%. The method has been used to evaluate the pharmacokinetics of Z and ZMP in man. The procedure should be applicable to the quantitation of certain other nucleosides and nucleotides in biological media.
Dixon
R
R
Gensia Pharmaceuticals, Inc., San Diego, CA 92121.
Fujitaki
J
J
Chrastil
L
L
Lee
J
J
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D012263:Ribonucleosides / Q000097:blood* / Q000493:pharmacokinetics; D014462:Ultrafiltration
D007093:Imidazoles; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine