目的 建立高效液相色谱-三重串联四级杆质谱（HPLC-MS/MS）联用同时测定丹荷颗粒中25种特征性成分（没食子酸、丹参素、儿茶素、绿原酸、咖啡酸、表儿茶素、芦丁、虎杖苷、金丝桃苷、紫云英苷、柚皮苷、橙皮苷、迷迭香酸、白藜芦醇、丹酚酸B、槲皮素、大黄素-8-O-β-D-葡萄糖苷、异鼠李素、大黄素、乌药碱、荷叶碱、隐丹参酮、丹参酮I、去氢荷叶碱、丹参酮II_A）含量的方法，并对其制剂批次间的一致性进行分析。方法 HPLC采用Agilent Rapid Resolution HD C₁₈色谱柱（50 mm×2.1 mm，1.8 μm），流动相为0.1%甲酸水溶液-0.1%甲酸乙腈溶液；质谱采用动态多反应监测（dMRM）扫描模式。对25种特征性成分进行含量测定。结果 建立的HPLC-MS/MS方法在10 min内完成了25种特征性成分的同时定量分析，定量限分别为异鼠李素、乌药碱、去氢荷叶碱0.025 ng/mL、大黄素、丹参酮I 0.050 ng/mL，大黄素-8-O-β-D-葡萄糖苷0.200 ng/mL，没食子酸、绿原酸、咖啡酸、表儿茶素、芦丁、金丝桃苷、紫云英苷、白藜芦醇、槲皮素、荷叶碱、丹参酮II_A 0.250 ng/mL，儿茶素、迷迭香酸、隐丹参酮0.500 ng/mL，丹参素、橙皮苷、丹酚酸B 1.000 ng/mL，虎杖苷2.000 ng/mL，柚皮苷5.000 ng/mL；且25种成分在各自质量浓度范围内线性关系良好（r>0.990 1），平均加样回收率85.16%~113.46%，RSD为2.01%~8.80%。此外，该方法较为全面地囊括了丹荷颗粒中君臣佐使药材的主要成分，25种成分总量为31.49 mg/g，其中丹酚酸B（9.44 mg/g）及橙皮苷（7.60 mg/g）质量分数最高，异鼠李素（0.79 μg/g）质量分数最低。经箱线图（Box-plot）分析，10个不同批次丹荷颗粒制剂中25种成分质量分数波动范围（P值）在75% < P < 125%；以及统计方法分析，25种成分质量分数的RSD在2.58%~13.10%；以上结果表明10批丹荷颗粒制剂间成分含量一致性合格。结论 所建立的分析方法快速、灵敏度高，结果真实可靠，能够为丹荷颗粒制剂的质量控制和制剂一致性分析提供科学方法及依据。

Objective A high performance liquid chromatography coupled to triple quadrupole mass spectrometry method (HPLC-MS/MS) was established to simultaneously determine the content of 25 characteristic components (gallic acid, tanshinol, catechin, chlorogenic acid, caffeic acid, epicatechin, rutin, polydatin, hyperin, astragalin, naringin, hesperidin, rosmarinic acid, resveratrol, salvianolic acid B, quercetin, emodin-8-O-β-D-glucoside, isorhamnetin, emodin, coclaurine, nuciferine, cryptotanshinone, tanshinone I, dehydronuciferine, tanshinone II_A) in Danhe Granules (DG), and the consistency between different batches was investigated. Methods The analysis was conducted on Agilent Rapid Resolution HD C₁₈ column (50 mm×2.1 mm, 1.8 μm) with the mobile phase of 0.1% formic acid water-0.1% formic acid acetonitrile. The dynamic multi-response detection (dMRM) scanning mode was used in the mass spectrometry. Results Based on the established HPLC-MS/MS method, the simultaneous quantitative analysis of 25 characteristic components could be completed within 10 min, with the quantitative limits of isorhamnetin, coclaurine, and dehydronuciferine of 0.025 ng/mL; emodin and tanshinone I of 0.050 ng/mL; emodin-8-O-β-D-glucoside of 0.200 ng/ml; gallic acid, chlorogenic acid, caffeic acid, epicatechin, rutin, hyperin, astragalin, resveratrol, quercetin, nuciferine, tanshinone II_A of 0.250 ng/ml; catechin, rosmarinic acid, and cryptotanshinone of 0.500 ng/mL; tanshinol, hesperidin, and salvianolic acid B of 1.000 ng/mL; polydatin of 2.000 ng/mL; naringin of 5.000 ng/mL, respectively. The linear relationships of the 25 constituents within their respective mass concentrations were good, with the average recovery of 85.16%-113.46% and the RSD of 2.01%-8.80%. Furthermore, this method also included the main components named monarch, minister, assistant and guide of herbs in a relatively comprehensive way. The total content of the 25 components was 31.49 mg/g, among which the content of salvianolic acid B (9.44 mg/g) and hesperidin (7.60 mg/g) was the highest, and the content of isorhamnetin (0.79 μg/g) was the lowest. According to boxplot analysis, the content of 25 components in 10 different batches of DG fluctuated (P value) within 75% < P < 125%; and the RSD value of 25 components ranged from 2.58% to 13.10% by statistical analysis. The above results showed that the consistency of the component content among 10 batches of DG was acceptable. Conclusion The analytical method established in this study is fast and sensitive. Furthermore, the results of this study are reliable and can provide scientific methods and basis for quality control and consistency analysis of DG.

国家"重大新药创制"项目（2019ZX09201004-001）；国家自然科学基金项目（81774155）；中央高校基本科研业务费专项资金资助项目（2019-JYB-XS-108）