In vitro interactions of TNO6 with human plasma

The ability of TNO6 to react with human plasma was investigated by in vitro incubation of plasma or plasma fractions with injectable TNO6. HPLC, ultrafiltration and flameless atomic absorption spectrophotometry were used to separate the platinum-containing chemical species and to measure the platinum content. The initial concentration of TNO6 in plasma declines very rapidly. The kinetics of the loss of initial TNO6 is very different from that of cisplatin loss. Most of the TNO6 is bound more quickly to proteins, while a little is transformed to less reactive or nonreactive platinum species. The level of final nonreactive platinum species depends on the particular plasma concerned. In addition, the reactivity of TNO6 towards proteins is very sensitive to Cl- concentration. The usefulness of HPLC for the study of TNO6 kinetics is demonstrated.