THE INTEGRITY OF CISPLATIN IN AQUEOUS AND PLASMA ULTRAFILTRATE MEDIA STUDIED BY PT-195 AND N-15 NUCLEAR-MAGNETIC-RESONANCE

Pt-195 and N-15 nuclear magnetic resonance (NMR) was used to study the chemical equilibria of cisplatin in water and plasma ultrafiltrate (P UF). Cisplatin was found to be stable for at least 2, but no longer th an 5 months in a reconstituted clinical formulation. as determined by Pt-195 NMR. In aqueous solution, the cis-PtCl2(NH3)(2) Pt-195 and N-15 NMR signal intensities decreased with time and the formation of [PtCl (H2O)(NH3)(2)](+) at pH values of 3.0, 6.5, 7.5 and 9.5 was observed w ithin 24 h of sample preparation. In addition, [Pt(H2O)(2)(NH3)(2)](+) was observed at pH 3.0, and [PtCl(OH)(NH3)(2)] and [Pt(OH)(2)(NH3)(2 )] were observed at pHs 7.5 and 9.5. During incubation of PUF with cis platin for 35 h, N-15 NMR signals for at least eight cisplatin derivat ives appeared at different times, whereas only four were observed by P t-195 NMR. With our NMR protocols, the detection limit for quantifiabl e cisplatin derivatives is estimated at 500 mu M using Pt-195 NMR and less than or equal to 200 mu M using N-15 NMR. In addition to providin g useful information about the chemical stability of cisplatin and der ivatives formed in aqueous solution, these magnetic resonance techniqu es, particularly N-15 NMR, can provide useful information about the me tabolism of cisplatin in biological regimes.