用于测定血浆和红细胞中N4-十六烷基-和N4-十八烷基-1-β-D-阿拉伯呋喃糖基胞嘧啶的灵敏高效液相色谱法。

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

作者信息

Rentsch K M, Schwendener R A, Schott H, Hänseler E

机构信息

Institute of Clinical Chemistry, University Hospital Zürich, Switzerland.

出版信息

J Chromatogr B Biomed Appl. 1995 Nov 17;673(2):259-66. doi: 10.1016/0378-4347(95)00261-1.

DOI:10.1016/0378-4347(95)00261-1

PMID:8611960

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.

摘要

N4-十六烷基-和N4-十八烷基-1-β-D-阿拉伯呋喃糖基胞嘧啶（NHAC，NOAC）是阿糖胞苷（ara-C）的两种新的细胞生长抑制剂衍生物，具有增强的细胞生长抑制活性和抗脱氨稳定性。建立了一种高效液相色谱（HPLC）方法，用于在使用275nm紫外检测的固相萃取后，特异性测定血浆和红细胞中的NHAC和NOAC。由于药物与蛋白质和膜的强烈结合，样品必须用尿素（血浆）或丁醇预处理并超声处理（红细胞）。两种药物的校准曲线在血浆浓度范围为20 - 2100微克/升、红细胞浓度范围为40 - 4200微克/升时均呈线性（r > 0.999）。日内和日间精密度研究显示重现性良好，变异系数低于8.5%。亲脂性阿糖胞苷衍生物的回收率大于66%。所描述的方法可应用于NHAC和NOAC的药代动力学研究。