HPLC-UV法测定皮肤给药后大鼠血浆5-(4-苯氧丁氧基)补骨脂素浓度

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (11): 1234-1239.

HPLC-UV法测定皮肤给药后大鼠血浆5-(4-苯氧丁氧基)补骨脂素浓度

郝彬, 李欣燕, 周向军, 王永祥

上海交通大学药学院King's Lab,上海 200240

收稿日期:2010-09-16 修回日期:2010-10-29 出版日期:2010-11-26 发布日期:2020-09-16
通讯作者: 王永祥,男,博士,教授,主要研究方向为转化药理学、聚乙二醇化药物研发和基因沉默技术。Tel: 021-34204763 E-mail: yxwang@sjtu.edu.cn
作者简介:郝彬,男,助理研究员,研究方向:药物代谢动力学。Tel: 021-34204772 E-mail: bhao@sjtu.edu.cn

Determination of plasma 5-(4-phenoxybutoxy) psoralen concentrations by HPLC-UV after dermal administration in rats

HAO Bin, LI Xin-yan, ZHOU Xiang-jun, WANG Yong-xiang

King's Lab, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

Received:2010-09-16 Revised:2010-10-29 Online:2010-11-26 Published:2020-09-16

摘要/Abstract

摘要： 目的: 建立大鼠血浆中5-(4-苯氧丁氧基)补骨脂素[5-(4-phenoxybutoxy) psoralen,PAP-1]高效液相色谱-紫外(HPLC-UV)测定方法, 并用于大鼠皮肤给药后血浆PAP-1浓度的测定。方法: 以异欧前胡素为内标,血浆样品经乙酸乙酯提取;应用Ultimate Column AQ-C₁₈色谱柱(150 mm×4.6 mm,5 μm);流动相为甲醇-水(75∶25),流速 0.8 mL/min, 检测波长311 nm;采用PAP-1与内标峰面积比值进行定量。大鼠皮肤给药PAP-1,检测不同时间血药浓度。结果: 本方法最低检测限为 5.3 μg/L(S/N＞10),线性范围为 5.3~2120 μg/L,血浆中PAP-1的日内和日间精密度为 2.3%~6.0%,准确度为102%~105%,回收率为 83.1%~86.5%。大鼠 15 mg/kg 皮肤给药后,PAP-1在4 h达峰。雄性和雌性大鼠的AUC分别为256和 1209 μg·L^-1·h,C_max分别为74和 225 μg/L。结论: 本方法专属性强、简便高效,可用于测定药物代谢动力学实验中PAP-1的浓度。本文首次报道大鼠PAP-1皮肤给药的药物动力学过程,药代参数存在明显的性别差异。

关键词: 5-(4-苯氧丁氧基)补骨脂素, 高效液相色谱-紫外法, 皮肤给药, 药代动力学, 性别差异

Abstract: AIM: To develop an analytical method for quantitation of plasma 5-(4-phenoxybutoxy) psoralen (PAP-1) concentrations after dermal administration in rats by using high-performance liquid chromatography with ultraviolet (HPLC-UV). METHODS: Plasma was extracted by ethyl acetate using isoimperatorin as an internal standard and separated by HPLC on a C₁₈ reversed-phase column using the mobile phase of methanol-water (75∶25,V/V) at a flow rate of 0.8 mL/min. PAP-1 was quantitated using the ratio of the area of the analyte to the area of the internal standard. Plasma concentrations of PAP-1 were determined after dermal administration. RESULTS: The limited of detection was 5.3 μg/L(S/N＞10). Calibration curves were linear over the range of 5.3 to 2120 μg/L. The intra and inter-assay variability ranged from 2.3% to 6.0%, and the accuracy ranged from 102% - 105%, for the low, medium and high quality control samples. The extraction recovery of PAP-1 from plasma was in the range of 83.1% to 86.5%. Following a single dermal dose of 15 mg/kg, the plasma PAP-1 level reached the peak at 4 h. AUC values were 256 and 1209 μg·L^-1·h while C_max values were 74 and 225 μg/L for male and female rats, respectively. CONCLUSION: The method is rapid, specific and sensitive, and can be used to determine plasma concentrations of PAP-1 for pharmacokinetic experiments. PAP-1 exhibits a significant gender differences after dermal administration in rats.

Key words: 5-(4-phenoxybutoxy) psorale (PAP-1), HPLC-UV, Dermal administration, Pharmacokinetics, Gender difference

中图分类号:

R969.1
R986

郝彬, 李欣燕, 周向军, 王永祥. HPLC-UV法测定皮肤给药后大鼠血浆5-(4-苯氧丁氧基)补骨脂素浓度[J]. 中国临床药理学与治疗学, 2010, 15(11): 1234-1239.

HAO Bin, LI Xin-yan, ZHOU Xiang-jun, WANG Yong-xiang. Determination of plasma 5-(4-phenoxybutoxy) psoralen concentrations by HPLC-UV after dermal administration in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(11): 1234-1239.

参考文献

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