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益母草膏给药后正常大鼠及寒凝血瘀型原发性痛经大鼠中益母草堿和水苏堿的比较药代动力学研究。

Comparative pharmacokinetics study of leonurine and stachydrine in normal rats and rats with cold-stagnation and blood-stasis primary dysmenorrhoea after the administration of Leonurus japonicus houtt electuary.

机构信息

School of pharmacy, China Medical University, Shenyang, P. R. China.

The Fourth Affiliated Hospital of China Medical University, Shenyang, P. R. China.

出版信息

J Sep Sci. 2019 May;42(9):1725-1732. doi: 10.1002/jssc.201801257. Epub 2019 Apr 9.

Abstract

Leonurus japonicus houtt, a well-known herb of traditional Chinese medicine, is widely used to treat gynaecological diseases. In this study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method for simultaneously quantifying leonurine and stachydrine, the two main bioactive components in Leonurus japonicus houtt, was developed and validated. Plasma samples were prepared by protein precipitation with acetonitrile and separation by a Hewlett Packard XDB-C8 column (150 × 4.6 mm, id, 5 μm) equipped with a gradient elution system containing methanol-water and 0.1% formic acid at a flow-rate of 0.4 mL/min. Components were then detected by a mass spectrometer in positive electrospray ionization mode. This method showed good linearity, precision, accuracy, recovery, stability, and negligible matrix effects, which were within acceptable ranges. The method was successfully applied to compare the pharmacokinetics in normal rats and rats with cold-stagnation and blood-stasis primary dysmenorrhoea treated with Leonurus japonicus houtt electuary. The result showed significant differences (p < 0.05) in the pharmacokinetic parameters between the primary dysmenorrhoea and normal groups. This result implied that Leonurus japonicus houtt electuary remained longer and was absorbed slower in rats with primary dysmenorrhoea and exhibited higher bioavailability and peak concentration.

摘要

益母草,一种广受欢迎的中药草药,被广泛用于治疗妇科疾病。本研究建立并验证了一种同时定量测定益母草中两种主要生物活性成分益母草碱和水苏碱的快速灵敏的液相色谱-串联质谱法。采用乙腈沉淀蛋白法提取血浆样品,用配备梯度洗脱系统(甲醇-水和 0.1%甲酸)的 Hewlett Packard XDB-C8 柱(150×4.6mm,内径,5μm,150×4.6mm,内径,5μm)进行分离,流速为 0.4mL/min。采用正电喷雾电离模式的质谱仪进行检测。该方法具有良好的线性、精密度、准确度、回收率、稳定性和可忽略的基质效应,均在可接受范围内。该方法成功地用于比较益母草膏在正常大鼠和寒凝血瘀型原发性痛经大鼠中的药代动力学。结果表明,原发性痛经组与正常组的药代动力学参数存在显著差异(p<0.05)。这表明原发性痛经大鼠中益母草膏的半衰期更长,吸收更慢,生物利用度更高,峰值浓度更高。

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