SENSITIVE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF N-4-HEXADECYL-1-BETA-D-ARABINOFURANOSYLCYTOSINE AND N-4-OCTADECYL-1-BETA-D-ARABINOFURANOSYLCYTOSINE IN PLASMA AND ERYTHROCYTES

N-4-Hexadecyl- and N-4-octadecyl-1-beta-D-arabinofuranosylcytosine (NH AC, NOAC) are two new cytostatic derivatives of cytosine arabinoside ( ara-C) with improved cytostatic activity and stability against deamina tion. A high-performance liquid chromatography (HPLC) method was devel oped for the specific determination of NHAC and NOAC in plasma and ery throcytes, after solid-phase extraction using UV detection at 275 nm. Because of the strong binding of the drugs to proteins and membranes, the samples have to be pretreated with urea (plasma) or butanol and ul trasonication (erythrocytes). The calibration curves are linear for bo th drugs (r>0.999) in the concentration ranges 20-2100 mu g/l for plas ma and 40-4200 mu g/l for erythrocytes, respectively. The within-day a nd between-day precision studies showed a good reproducibility, with c oefficients of variation below 8.5%. The recoveries of the lipophilic ara-C derivatives are greater than 66%. The method described can be ap plied to pharmacokinetic studies with NHAC and NOAC.