Plasma analysis of alpha-difluoromethylornithine using pre-column derivatization with naphthalene-2,3-dicarboxaldehyde/CN and multidimensional chromatography

A procedure for the plasma analysis of alpha-difluoromethylornithine (DFMO) has been developed that utilizes pre-column derivatization with naphthalen e-2,3-dicarboxaldehyde/cyanide (NDA/CN) in pH 9.2 berate buffer. Selective derivatization of delta-amine of DFMO followed by quenching of the reaction results in the formation of a cyanobenz[f] isoindole (CBI) derivative that is stable for 24 h. Plasma was prepared for derivatization by a single ste p procedure which resulted in an ultrafiltrate compatible with derivatizati on and analysis. The DFMO derivative (CBI-DFMO) was separated from plasma i nterferences by multidimensional chromatography with an analysis time of 28 min. The response for DFMO in plasma was linear over the range of 2.1 x 10 (-8) - 2.1 x 10(-6) M after derivatization. This procedure encompasses a us eful linear range and offers the advantages of minimal sample preparation a nd production of a stable fluorophor. (C) 1998 Elsevier Science B.V. All ri ghts reserved.