盐酸川芎嗪在小鼠体内的药代动力学和心脏分布研究

Study on the pharmacokinetics and cardiac distribution of tetramethylpyrazine hydrochloride in mice

目的建立盐酸川芎嗪(TMP)检测的反相高效液相色谱法(RP-HPLC)并研究TMP在小鼠体内的药代动力学过程和心脏分布情况。方法建立乙腈沉淀小鼠血浆和心脏匀浆的RP-HPLC检测方法。小鼠腹腔单次注射TMP 80mg·kg^(-1)后,在不同时间点测定血浆及心脏匀浆液中TMP的浓度,用DAS2.0计算TMP的药代动力学参数。结果该方法在TMP浓度为0.2~20.0mg·L^(-1)内有良好的线性(r=0.999 7)、回收率和精密度。血浆TMP的主要药代动力学参数:AUC_(0-t)为(671.20±31.49)mg·min·L^(-1),C_(max)为(17.54±0.71)mg·L^(-1),t_(max)为10 min,t_(1/2)为(25.47±14.85)min。结论 RP-HPLC法适用于小鼠血浆和心脏匀浆中TMP的检测,准确可靠、灵敏度高,TMP吸收迅速、在心脏有较高的分布,有利于心脏疾病的治疗。

Objective To investigate the pharmacokinetics and cardiac distribution of tetramethylpyrazine（ TMP） hydrochloride in mice by reversed phase high performance liquid chromatography（ RP- HPLC）method. Methods The plasma and heart homogenate of mice were treated with acetonitrile and a RP- HPLC method was developed. The 66 mice were injected intraperitoneally with a single dose of 80 mg·kg^-1.The concentration of TMP in plasma and heart was determined. The parameters of the pharmacokinetics were calculated. Results This RP-HPLC method had a good linearity,recovery rate and precision. The standard curve of TMP was linear in the range of 0. 2- 20. 0 mg · L^-1（ r = 0. 999 7）. The major parameters of TMP were as follow： AUC（0- t） was（ 671. 20 ± 31. 49） mg·min·L^-1,C（max） was（ 17. 54 ± 0. 71） mg·L^-1,t（max）was 10 min,t（1 /2）was（ 25. 47 ± 14. 85） min. Conclusion A simple,accurate and sensitivity RP- HPLC method is developed and validated for the determination of TMP concentration in plasma and heart of mice. TMP has a rapid absorption and higher concentration in the heart,which was beneficial for the treatment of heart disease.