Automated quantitative determination of a new polyamine biosynthesis inhibitor (CGP 48 664) and a potential metabolite in human and animal plasma by high-performance liquid chromatography.
A specific and sensitive liquid chromatographic assay for the determination of 4-amidino-1-indanone-2'-amidinohydrazone (CGP 48 664, I) and a potential metabolite, 2-(4-carbamoyl-2,3-dihydro-1H-inden-1-yliden) hydrazine carboximidamide (CGP 53 391, II), in human and animal plasma was developed. CGP 51 467, a structural analog, was added to the plasma samples (up to 1 ml) as an internal standard. After mixing, the samples were processed automatically using an ASPEC solid-phase extraction system. The final extracts were chromatographed on a 5 microns Purospher RP-18 HPLC column. Chromatography was performed using a gradient system and UV detection. The described HPLC method is suitable for specific and quantitative measurement of concentrations of I, as well as its potential metabolite II down to 5-10 ng/ml in human and animal (dog, rat) plasma with acceptable reproducibility and accuracy.
Degen
P H
PH
Research and Development Department, Ciba-Geigy Limited, Basel, Switzerland.
Zbinden
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D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000578:Amidines / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D001322:Autoanalysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000097:blood*; D006146:Guanidines / Q000097:blood; D006801:Humans; D006835:Hydrazones / Q000097:blood; D007189:Indans / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D012044:Regression Analysis; D012680:Sensitivity and Specificity
D000578:Amidines; D004791:Enzyme Inhibitors; D006146:Guanidines; D006835:Hydrazones; D007189:Indans; C082408:4-amidinoindan-1-one 2'-amidinohydrazone; C102071:CGP 53391; D012437:Adenosylmethionine Decarboxylase