川芎嗪硝酮衍生物在大鼠体内的组织分布研究

Study on tissue distribution of nitrone derivative of tetramethylpyrazine in rats

目的对正常大鼠体内川芎嗪(TMP)硝酮衍生物:(2-N-叔丁基硝酮)-3,5,6-三甲基吡嗪(2-[[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethylpyrazine,TBN)的组织分布进行研究。方法用Purospher C18柱(4.6mm×150.0 mm,5μm),以甲醇-0.05 mol.L-1磷酸二氢钾水溶液(45∶55,pH3)为流动相,检测波长为295 nm,建立大鼠血浆及组织内TBN含量分析的HPLC-UV方法,用于组织分布研究。结果静脉(80 mg.kg-1)给药后,TBN在各种组织的AUC0-360在2.48～13.74 mg.min.g-1,从高到低依次为:血浆>肺>肾>肝>脾>脑>心;MRT0-360在129.50～161.95 min,由长到短依次为:肺>脾>肾>脑>肝>心>血浆。结论本研究建立的HPLC方法专属性强、简便、快速、准确;用此法得知,TBN静脉给药后,可快速分布于各组织中,包括脑组织。

Objective To investigate the tissue distribution of nitrone derivative of tetramethylpyrazine （ TMP）, 2 - [ [ （ 1,1 - dimethylethyl） oxidoimino ] methyl ] - 3,5,6 - trimethyl - pyrazine （TBN） in rats. Methods A validated HPLC -UV method was developed to assay the TBN concentration in plasma and tissues so that to identify the tissue distribution behaviour. Purospher ODS C,s column （4.6 mm × 150. 0 mm, 5 μm） was used for separation with methanol -0. 05 mol · L^-1 potassium dihydrogcn phosphate solution （45： 55, pH 3. 0） as mobile phase and 295 nm as detecting wavelength. Results After intravenous administration （80 mg· kg^-1）, the AUC0-360 of TBN in different tissues ranged from 2. 48 -13.74 mg·min · g^-1, the sequence from high to low was： plasma 〉 lung 〉 kidney 〉 liver 〉 spleen 〉 brain 〉 heart. The MRT0-360 was in the range of 129.50 - 161.95 min, the sequence from long to short was ： lung 〉 spleen 〉 kidney 〉 brain 〉 liver 〉 heart 〉 plasma. Conclusion A simple rapid HPLC method with high specificity and acceptable accuracy was developed. The tissue distribution information of TBN obtained by the HPLC method. The tissue distribution results of TBN showed that TBN distributed fast into tissues including brain after intravenous administration.