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高效液相色谱-荧光检测法测定兔血浆中3-正丁基苯酞及其在药代动力学研究中的应用

Determination of 3-n-butylphthalide in rabbit plasma by HPLC with fluorescence detection and its application in pharmacokinetic study.

作者信息

Zhao Chunshun, He Zhonggui, Cui Shengmiao, Zhang Ruhua

机构信息

Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.

出版信息

Biomed Chromatogr. 2003 Sep;17(6):391-5. doi: 10.1002/bmc.255.

DOI:10.1002/bmc.255
PMID:13680850
Abstract

A rapid, sensitive and specific reversed-phase high-performance liquid chromatographic method was developed for the determination of 3-n-butylphthalide, a drug currently being developed for treatment of stroke, in rabbit plasma. Fluorescence detection at an excitation wavelength of 280 nm and an emission wavelength of 304 nm was used for quantification of 3-n-butylphthalide. Ibuprofen was used as internal standard. Plasma samples were extracted with diethyl ether under acidic conditions. After evaporation of the organic phase, the extract was dissolved in mobile phase and injected into the chromatograph with C(18) column and a mobile phase of 0.05 mol/L sodium acetate buffer (pH 4.5)-acetonitrile (400:600). The peak area ratio vs concentration in plasma was linear over the range of 0.0212-4.24 microg/mL (correlation coefficient r = 0.9984) and the limit of quantification was 0.0212 microg/mL. Mean recovery was determined as 101.0% by analysis of plasma standard samples containing 0.0424, 0.424, 2.12 and 4.24 microg/mL of 3-n-butylphthalide. The intra-day relative standard deviations (RSDs) ranged from 3.6 to 8.9% and inter-day RSDs were within 8.0%. Pharmacokinetics of a single intravenous dose of 3-n-butylphthalide to the rabbits was presented to illustrate the applicability of this method. 3-n-Butylphthalide exhibited linear pharmacokinetics after intravenous administration to rabbits over the dose range 1-10 mg/kg.

摘要

建立了一种快速、灵敏且特异的反相高效液相色谱法,用于测定兔血浆中3-正丁基苯酞,该药物目前正处于治疗中风的研发阶段。采用激发波长为280nm、发射波长为304nm的荧光检测法对3-正丁基苯酞进行定量。布洛芬用作内标。血浆样品在酸性条件下用乙醚萃取。有机相蒸发后,提取物溶解于流动相中,注入配备C(18)柱、流动相为0.05mol/L醋酸钠缓冲液(pH4.5)-乙腈(400:600)的色谱仪中。血浆中峰面积比与浓度在0.0212 - 4.24μg/mL范围内呈线性关系(相关系数r = 0.9984),定量限为0.0212μg/mL。通过分析含0.0424、0.424、2.12和4.

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