A method, based on the in vitro inhibition of purified human DNA polymerase .alpha., the major enzyme of DNA replication, was developed, allowing the rapid and accurate determination of pmol amounts of aphidicolin, a promising anticancer drug. The efficacy of this simple method was verified by the determination of aphidicolin in the liver, spleen, blood and urine of mice treated parenterically with the drug. Given its sensitivity and the avoidance of radioactive tracers, this enzymatic method is suitable for determination of the drug in body fluids and tissue biopsies from living humans. It allows the detection and quantification of aphidicolin in the presence of inactive metabolite(s) with very similar chemical structure(s) such as those generated by liver microsomal oxidases. The technique is also useful in monitoring the purification of the drug from cultures of Cephalosporium aphidicola.
AN ENZYMATIC METHOD FOR MICRO DETERMINATION OF APHIDICOLIN A PROMISING ANTI CANCER DRUG
FOCHER F;
1981
Abstract
A method, based on the in vitro inhibition of purified human DNA polymerase .alpha., the major enzyme of DNA replication, was developed, allowing the rapid and accurate determination of pmol amounts of aphidicolin, a promising anticancer drug. The efficacy of this simple method was verified by the determination of aphidicolin in the liver, spleen, blood and urine of mice treated parenterically with the drug. Given its sensitivity and the avoidance of radioactive tracers, this enzymatic method is suitable for determination of the drug in body fluids and tissue biopsies from living humans. It allows the detection and quantification of aphidicolin in the presence of inactive metabolite(s) with very similar chemical structure(s) such as those generated by liver microsomal oxidases. The technique is also useful in monitoring the purification of the drug from cultures of Cephalosporium aphidicola.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
