DETERMINATION OF ALPHA-DIFLUOROMETHYLORNITHINE IN BLOOD BY MICRODIALYSIS SAMPLING AND CAPILLARY ELECTROPHORESIS WITH UV DETECTION

A procedure is described for the analysis of cu-difluoromethylornithin e (DFMO), an anti-cancer agent, in plasma microdialysis (MD) samples. DFMO has been shown to be effective alone or in combination with other agents in the treatment of several cancers. Precolumn derivatization of DFMO with naphthalene-2,3-dicarboxaldehydecyanide (NDA-CN) in pH 10 .0 berate buffer results in the rapid formation of a stable mono-deriv atized product (N-substituted 1-cyanobenz[f]isoindole, CBI), which is UV active. An analytical method has been developed to separate CBI-DFM O from NDA-CN derivatization products of 20 standard amino acids using capillary electrophoresis (CE). This method is then employed for the determination of DFMO in plasma microdialysis samples. Separation of D FMO from other components in the dialysate was achieved within 20 min. The response for DFMO in Ringer's solution was linear over the range of 1.2 . 10(-6) to 1.6 . 10(-4) M after derivatization. The detection limit of DFMO in the plasma dialysate is 5 mu M using UV detection at 254 nm. This method has been proven to have adequate sensitivity for q uantitation of DFMO in i.v. microdialysate samples and has been succes sfully applied to monitoring the pharmacokinetics of DFMO by CE-UV.