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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 establish a reverse-phase high-performance liquid chromatography (RP-HPLC) for the determination of tetramethylpyrazine hydrochloride (TMP) and to study the pharmacokinetics and cardiac distribution of TMP in mice. Methods The RP-HPLC method for the determination of plasma and cardiac homogenates in acetonitrile-precipitated mice was established. After a single intraperitoneal injection of TMP (80 mg · kg -1), the concentrations of TMP in plasma and cardiac homogenates were measured at different time points. The pharmacokinetic parameters of TMP were calculated by DAS 2.0. Results The method showed good linearity (r = 0.999 7), recovery and precision at a TMP concentration of 0.2-20.0 mg · L -1. The main pharmacokinetic parameters of plasma TMP were as follows: AUC_ (0-t) was (671.20 ± 31.49) mg · min · L -1 and C max was (17.54 ± 0.71) mg · L -1 ), t max for 10 min and t 1/2 for 25.47 ± 14.85 min. Conclusion The RP-HPLC method is suitable for the detection of TMP in plasma and cardiac homogenate of mice. It is accurate and reliable, has high sensitivity, rapid absorption of TMP and high distribution in the heart, which is good for the treatment of heart disease.