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


Rentsch, K M; Schwendener, R; Schott, H; Hänseler, E (1995). Sensitive high-performance liquid chromatographic method for the determination of N4-hexadecyl- and N4-octadecyl-1-beta-D-arabinofuranosylcytosine in plasma and erythrocytes. Journal of Chromatography. B, Biomedical Applications, 673(2):259-266.

Abstract

N4-Hexadecyl- and N4-octadecyl-1-beta-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 mm. Because of the strong binding of the drugs to proteins and membranes, the samples have to be pretreated with urea (plasma) or butanol and ultrasonication (erythrocytes). The calibration curves are linear for both drugs (r > 0.999) in the concentration ranges 20-2100 micrograms/l for plasma and 40-4200 micrograms/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.

N4-Hexadecyl- and N4-octadecyl-1-beta-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 mm. Because of the strong binding of the drugs to proteins and membranes, the samples have to be pretreated with urea (plasma) or butanol and ultrasonication (erythrocytes). The calibration curves are linear for both drugs (r > 0.999) in the concentration ranges 20-2100 micrograms/l for plasma and 40-4200 micrograms/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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1995
Deposited On:20 Oct 2009 13:32
Last Modified:05 Apr 2016 13:30
Publisher:Elsevier
ISSN:1572-6495
Publisher DOI:10.1016/0378-4347(95)00261-1
PubMed ID:8611960
Permanent URL: http://doi.org/10.5167/uzh-23332

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