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Sensitive high-performance liquid chromatographic method for the determination of N4-hexadecyl- and N4-octadecyl-1-ß-d-arabinofuranosylcytosine in plasma and erythrocytes

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Abstract

N4-Hexadecyl- and N4-octadecyl-1-ß-d-arabinofuranosylcytosine (NHAC, NOAC) are two new cytostatic derivatives of cytosine arabinoside (ara-C) with improved cytostatic activity and stability against deamination. A high-performance liquid chromatography (HPLC) method was developed for the specific determination of NHAC and NOAC in plasma and erythrocytes, 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 ultasonication (erythrocytes). The calibration curves are linear for both drugs (r > 0.999) in the concentration ranges 20–2100 μg/l for plasma and 40–4200 μg/l for erythrocytes, respectively. The within-day and between-day precision studies showed a good reproducibility, with coefficients of variation below 8.5%. The recoveries of the lipophilic ara-C derivatives are greater than 66%. The method described can be applied to pharmacokinetic studies with NHAC and NOAC.

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