High-performance liquid chromatographic assay of the antineoplastic agent tricyclic nucleoside 5'-phosphate and its disposition in rabbit.

Anion-exchange and reversed-phase high-performance liquid chromatographic procedures are described for the assay of the antineoplastic agent tricyclic nucleoside 5'-phosphate (TCNP) and its metabolite tricyclic nucleoside (TCN) in biological fluids. Disposition of TCNP has been studied in rabbit. TCNP is eliminated from blood and plasma with a biologic half-life of about 7.5 h. Apparent volume of distribution is 43.2 l/m2 and total body plasma TCNP clearance is 67.8 ml/min/m2. TCNP is hydrolyzed by plasma and probably other tissues to TCN which is present in blood and plasma at about one-tenth the concentration of TCNP. There is no accumulation of TCNP or TCN in blood or plasma over 2 days of administration. In 24 h 2.4% of a dose of TCNP is excreted in bile of a rabbit with a cannulated bile duct as unchanged TCNP and 30.7% as TCN. TCN is excreted in bile at an initial concentration half the maximum solubility of TCN in rabbit bile. Excretion of TCNP and TCN over 24 h in the urine of a rabbit with a cannulated bile duct is 1.5% and 5.2% of the dose, respectively.