ANALYSIS OF 2-DIFLUOROMETHYL-DL-ORNITHINE IN HUMAN PLASMA, CEREBROSPINAL-FLUID AND URINE BY CATION-EXCHANGE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

An analytical method has been developed based on cation-exchange liqui d chromatography for the measurement of 2-difluoromethyl-DL-ornithine (DFMO) in human plasma, cerebrospinal fluid (CSF) and urine. Fluoresce nce detection at excitation-emission wavelengths of 340/440 nm is foll owed by postcolumn derivatization with o-phthalaldehyde-2-mercaptoetha nol. All calibration ranges yielded linear relationships with correlat ion coefficients better than 0.999. In each case the limit of quantita tion was equal to the lowest value of the standard curve. The variabil ity of the assay, expressed as relative standard deviations, was less than 7.1%, 15.3% and 7.1% for plasma, CSF and urine, respectively. The accuracy of the assay (expressed as relative errors) ranged between - 4.3% and 2.0% for plasma analysis, between -0.1% and 14.0% for CSF ana lysis and between -8.0% and 2.0% for urine analysis. Plasma, CSF and u rinary DFMO concentrations were measured in samples obtained from pati ents undergoing treatment for trypanosomiasis. The method was found to be applicable for the measurement of DFMO levels in human body fluids for the determination of pharmacokinetic parameters in clinical studi es.