Tissue Distribution and Lactone Stability of 9-Nitrocamptothecin in Rats

The tissue distribution and lactone stability of 9-nitrocamptothecin(9-NC)were investigated following intravenous administration of 9-NC solution to rats.The validated HPLC method was developed for determination of 9-NC lactone form(lactone 9-NC)and the total of lactone and carboxylate forms(total 9-NC)in rat tissue and plasma simultaneously.After iv administration of 9-NC solution,the concentrations of lactone and total 9-NC in rat tissues and plasma were measured.Then the lactone percentages,and the index of lactone stability were calculated. It was found that lactone 9-NC was unstable in liver and lactone percentage was even lower than that in plasma.In other tissues,however,lactone 9-NC was more stable and lactone percentages were almost all higher than that in plasma.In addition,the lactone percentage in plasma,kidney and small intestine decreased with time.Lactone 9-NC was more stable in tissues except liver than in plasma.