Analytical techniques applied to the study of radiosensitizing drugs and of their metabolites

The sensitizing effect of a given drug is directly related to its concentration in the irradiated site, and consequently it is important to know the kinetics both with respect to its metabolic stability and its rate of penetration in order to optimize treatments and obtain maximum effectiveness. It is desirable that the radiosensitizer should diffuse unchanged into the tissue prior to the irradiation even if, in some cases, the products of drug metabolism are still active in cellular sensitization. It is relevant in this respect to know the kinetics of absorption, distribution and elimination of the drugs from a patient's body. The present interest is focussed mainly on nitroimidazole derivatives as radiosensitizers of hypoxic cells. Knowledge of the transformation mechanisms of the major metabolites of these compounds, and of techniques applicable for their identification and analysis is very useful in investigations on the utilization of these drugs. A survey of the most usable analytical techniques is presented. (Auth.)