An admonition when measuring the lipophilicity of radiotracers using counting techniques

Log P measurements are a fundamental physico-chemical parameter and one of the cornerstones of structure-activity relationships in medicinal chemistry . Despite the attractiveness of the method, the use of counting techniques to measure the log P of lipophilic radiotracers is fraught with pitfalls du e to the amplifying effects of small quantities of radioactive impurities. For example, a radiotracer with a log P of 4 containing only 0.1% of a radi oactive impurity with a log P of -1 will have an apparent log P of 3 if mea sured using conventional shake-flask partition techniques, counting the rad ioactivity in each phase. However, pre-washing the radiotracer-containing o rganic phase with aqueous phase can, in many cases, allay doubts about the validity of such measurements. (C) 2001 Elsevier Science Ltd. All rights re served.