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反相高效液相色谱法测定大鼠鼻腔给予齐多夫定后血浆中的药物浓度及其药代动力学。

Reversed phase HPLC determination of zidovudine in rat plasma and its pharmacokinetics after a single intranasal dose administration.

机构信息

Departamento de Farmácia, Universidade Estadual do Centro-Oeste/UNICENTRO, Guarapuava, PR, Brazil 85040-080.

出版信息

Biol Res. 2009;42(3):357-64. Epub 2009 Nov 2.

Abstract

The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of zidovudine in rat plasma and its application to a pharmacokinetic study following a single intranasal dose zidovudine is described. Zidovudine was extracted from the plasma using a single-step deproteinization. Chromatographic separation of zidovudine from interfering components was achieved with a C-18 reverse phase column, a mobile phase consisting of a mixture of sodium acetate buffer (55 mM) with pH adjusted to 7.0 and acetonitrile (91:9 v/v) and UV detection set at 265 nm. The method was linear from 100 to 10,000 ng.mL(-1) (r(2) > or = 0.9995), and zidovudine had a mean recovery from plasma of 92.8%. The coefficient of variation of inter-day and intra-day quality control samples was less than 15%. After a single intranasal dose of zidovudine administered to rats, pharmacokinetic parameters (AUC(0-24), C(max), t(max), t(1/2)) were determined. The proposed method was found to be simple, specific, accurate, and precise and could be applied to the quantitative analysis of clinical pharmacokinetic studies of zidovudine in rats.

摘要

建立并验证了一种 HPLC-UV 法,用于检测大鼠血浆中的齐多夫定,并将其应用于单次鼻腔给予齐多夫定后的药代动力学研究。齐多夫定经一步蛋白沉淀法从血浆中提取。采用 C18 反相柱,以乙酸钠缓冲液(55mM)与 pH 调至 7.0 的混合液-乙腈(91:9v/v)为流动相,在 265nm 处进行紫外检测,实现了齐多夫定与干扰成分的色谱分离。该方法在 100-10000ng·mL-1(r2≥0.9995)范围内呈线性,齐多夫定从血浆中的平均回收率为 92.8%。日内和日间质控样品的变异系数均小于 15%。单次鼻腔给予齐多夫定后,测定了大鼠的药代动力学参数(AUC(0-24)、Cmax、tmax、t1/2)。该方法简单、特异、准确、精密,可用于大鼠齐多夫定临床药代动力学研究的定量分析。

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