Hellmuth R. Hinz

Stabilities of 3H- and 2H-labelled camptothecins

Commercially available [ 3 H]-camptothecin, labeled mainly at the C-5 position, had partially lost the tritium label after recovery from the plasma of a patient injected with this drug or after incubation in plasma at 38°C for 72 h. Camptothecin dissolved in CH 3 0 2 H/ 2 H 2 O, incorporated deuterium at the C-5 position with a 50% uptake after one day at pH 11.0 or after 10-11 days at pH 7.4. At pH 2.0, the deuterium uptake was negligible. Camptothecin, dissolved in deuterated sulfuric acid, incorporated 37 or 80% deuterium at C-14 when heated to 65 or 80°C, respectively. Commercially available [ 3 H]-camptothecin, labeled mainly at the C-5 position, is thus not useful for in vivo metabolism or pharmacokinetic studies due to rapid loss of tritium in plasma. In contrast, [ 3 Hl-camptothecin prepared as described in this paper for [ 2 H]-camptothecin is expected to be useful.