To investigate the effect of ligustrazine on the pharmacokinetic profile of tanshinol after intravenous administration in rats, a sensitive liquid chromatography tandem mass spectrometry method was developed and validated for quantitative determination of tanshinol and ligustrazine in rat plasma. After prepared by protein precipitation, the analytes were separated on a Waters Acquity HSS T3 column (100 × 2.1 mm, 1.8μm) and eluted by 0.1% formic acid in water and acetonitrile at a flow rate of 0.4 ml/min. The precursor–product ion transitions were m /z 197.0 → 135.0 for tanshinol, m /z 417.1 → 255.1 for liquiritin (internal standard) in negative ion mode and m /z 137.1 → 55.0 for ligustrazine in positive ion mode. To avoid the interference of tanshinol metabolite transformation, the stability of analytes in samples collected after administration was assessed. The validated method was successfully applied to a pharmacokinetic study after intravenous administration of single tanshinol and Danshen Chuanxiongqin Injection. After Danshen Chuanxiongqin injection administration, the values of elimination half‐time, area under the concentration–time curve and C_o were 0.36 ± 0.13 h, 1.29 ± 0.37 μg/ml h and 10.51 ± 2.58 μg/ml for male rats, respectively. In the single tanshinol group, the corresponding values were 0.56 ± 0.24 h, 1.85 ± 0.44 μg/ml h and 14.11 ± 2.26 μg/ml for male rats—30–40% higher than those for the Danshen Chuanxiongqin Injection group. There was a significant different between male and female rats. This study provided information on the influence of ligustrazine on the pharmacokinetic characteristics of tanshinol after intravenous administration of Danshen Chuanxiongqin Injection in rats, which will be helpful for its clinical application.

中文翻译：

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丹参醇和丹参川xi嗪注射液静脉注射后丹参醇和川gust嗪在大鼠血浆中的药代动力学研究。

为了研究川gust嗪对丹参醇在大鼠静脉内给药后药代动力学的影响，建立了一种灵敏的液相色谱串联质谱法，用于定量测定大鼠血浆中丹参醇和川gust嗪的有效性。通过蛋白质沉淀制备后，将分析物在Waters Acquity HSS T3色谱柱（100×2.1 mm，1.8μm）上分离，并用0.1％甲酸的水和乙腈溶液以0.4 ml / min的流速洗脱。丹参酚的前体-产物离子跃迁为m / z 197.0→135.0，负离子模式下的liquiritin（内标）为m / z 417.1→255.1，m / z川gust嗪在正离子模式下为137.1→55.0。为了避免丹参醇代谢物转化的干扰，对给药后收集的样品中分析物的稳定性进行了评估。单次丹参醇和丹参川xi嗪注射液静脉滴注后，已验证的方法成功地用于药代动力学研究。丹参川xi嗪注射液给药后，消除半衰期，浓度-时间曲线下面积和C _o值雄性大鼠分别为0.36±0.13 h，1.29±0.37μg/ ml h和10.51±2.58μg/ ml。在单丹参醇组中，雄性大鼠的相应值为0.56±0.24 h，1.85±0.44μg/ ml h和14.11±2.26μg/ ml，比丹参川xi嗪注射液组高30–40％。雄性和雌性大鼠之间存在显着差异。本研究提供了川gust嗪对丹参川xi嗪注射液大鼠静脉内丹参醇药代动力学特性影响的信息，将有助于其临床应用。