Determination of alpha-difluoromethylornithine in blood by microdialysis sampling and capillary electrophoresis with UV detection.
A procedure is described for the analysis of alpha-difluoromethylornithine (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-dicarboxaldehyde-cyanide (NDA-CN) in pH 10.0 borate buffer results in the rapid formation of a stable mono-derivatized product (N-substituted 1-cyanobenz[f]isoindole, CBI), which is UV active. An analytical method has been developed to separate CBI-DFMO 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 DFMO 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 x 10(-6) to 1.6 x 10(-4) M after derivatization. The detection limit of DFMO in the plasma dialysate is 5 microM using UV detection at 254 nm. This method has been proven to have adequate sensitivity for quantitation of DFMO in i.v. microdialysate samples and has been successfully applied to monitoring the pharmacokinetics of DFMO by CE-UV.
Hu
T
T
Center for Bioanalytical Research, University of Kansas, Lawrence 66047, USA.
Zuo
H
H
Riley
C M
CM
Stobaugh
J F
JF
Lunte
S M
SM
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D000518:Eflornithine / Q000097:blood* / Q000493:pharmacokinetics; D019075:Electrophoresis, Capillary; D007202:Indicators and Reagents; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D012996:Solutions; D000518:Eflornithine