Trace analysis for cis-platinum anti-cancer drugs via LCEC.

Liquid chromatography-electrochemical detection (LCEC) methods and instrumentation have been successfully applied for the trace determination of at least three separate platinum (Pt) anti-cancer (neoplastic) agents. All of these compounds have proven clinically effective in the treatment of human neoplasms. The three Pt derivatives studied were: cis-dichloro diammine platinum (cis-Pt); cis-diammine-1, 1-cyclobutane dicarboxylate platinum (CBDCA); and cis-dichloro-trans-dihydroxy diisopropylamine platinum (CHIP). The parent compound, cis-Pt (CDDP), can be determined via both oxidative and reductive LCEC, with differences in the minimum limits of detection. Calibration plots and minimum detection limits have been determined for all three derivatives. Both CBDCA and CHIP can be determined via direct LCEC, but the minimum detection limits for CBDCA are not practical for stability or clinical studies. A new method of derivatization for CBDCA and related Pt compounds has been developed, wherein this can be quantitatively converted to cis-Pt, and the final derivative is then determined as for the parent cis-Pt. CDDP can be determined via reductive LCEC at the 100-ppb level in plasma. The final methods of LCEC analysis have now been applied to a variety of stability studies with all three Pt drugs, in water, plasma, and saline infusion solutions. It is suggested that these LCEC methods are directly applicable and amenable to "real world" clinical settings and cancer-patient samples.