目的 建立基于UPLC-Q-Orbitrap HRMS的丹灯通脑软胶囊（DTSC）中多种活性成分定量分析方法，并采用主成分分析（PCA）法对其质量进行综合评价。方法 采用Acquity UPLC^® BEH C₁₈色谱柱（50 mm×2.1 mm，1.7μm），以乙腈-0.1%甲酸水溶液为流动相进行梯度洗脱，以实现化合物的前期分离；然后通过Q-Orbitrap MS正负离子同时监测、一级全扫描及自动触发二级质谱扫描的模式捕捉目标成分的精确相对分子质量及碎片离子信息，以实现对待测物的准确定性和定量；最后将定量结果与PCA法相结合对不同批次药物进行科学的质量评价分析。结果 在优化的色谱、质谱条件下，甜菜碱、丹参素、绿原酸、原儿茶醛、葛根素、咖啡酸、木犀草苷、迷迭香酸、丹酚酸A、丹酚酸B、槲皮素、芹菜素、洋川芎内脂A、二氢丹参酮I、丹参酮I、隐丹参酮和丹参酮Ⅱ_A分别在0.018 1～0.578 4、5.555 7～177.782 0、0.018 1～0.580 3、0.002 8～0.089 2、0.787 2～25.191 3、0.000 5～0.016 7、0.007 2～0.228 9、0.065 8～2.105 3、0.304 6～9.747 1、3.888 1～124.417 6、0.000 5～0.016 0、0.000 6～0.018 1、0.002 5～0.080 1、0.019 8～0.632 8、0.032 2～1.031 7、0.102 8～3.290 0、0.044 5～1.422 9 μg/mL线性关系良好（r≥0.999 2）；精密度、重复性及稳定性良好（RSD≤5%）；加样回收率在98%～102%，RSD均小于3%；定量分析结果表明大多数批次药物质量较为稳定，其中丹参酮I、隐丹参酮、二氢丹参酮I和丹参酮Ⅱ_A对药物质量具有较大影响，可对其进行重点监控以保证药物批次质量。结论 建立的定量方法灵敏度高且准确性好，方法学考察结果符合测定要求，可用于DTSC中多种活性成分的快速测定；并为其质量评价提供新的科学依据和参考。

Objective To establish a quantitative analysis method of multiple active components in Dandeng Tongnao Soft Capsule (DTSC) based on ultra performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), and conduct a quality assessment using principal component analysis. Methods The column was Acquity UPLC^® BEH C₁₈ (50 mm×2.1 mm, 1.7 μm) and the mobile phase was consisted of acetonitrile-water (containing 0.1% formic acid) with gradient elution; the information of accurate mass and fragment ions was obtained by the novel "monitored simultaneously for positive and negative ions, full MS scan and automatic trigger secondary mass spectrometry" mode of Q-Orbitrap MS technology to ensure the accurate qualitation and quantitation of the analytes; the results of the contents were then combined with the principal component analysis to achieve the scientific assessment of the different batches of drugs. Results Under the optimized conditions, betaine, danshensu, chlorogenic acid, protocatechuic aldehyde, puerarin, caffeic acid, galuteolin, rosmarinic acid, salvianolic acid A, salvianolic acid B, quercetin, apigenin, senkyunolide A, dihydrotanshinone I, tanshinone I, cryptotanshinone, and tanshinon Ⅱ_A all showed good liner relationship (r ≥ 0.999 2) in the range of 0.018 1-0.578 4, 5.555 7-177.782 0, 0.018 1-0.580 3, 0.002 8-0.089 2, 0.787 2-25.191 3, 0.000 5-0.016 7, 0.007 2-0.228 9, 0.065 8-2.105 3, 0.304 6-9.747 1, 3.888 1-124.417 6, 0.000 5-0.016 0, 0.000 6-0.018 1, 0.002 5-0.080 1, 0.019 8-0.632 8, 0.032 2-1.031 7, 0.102 8-3.290 0, and 0.044 5-1.422 9 μg/mL, respectively; The results of the accuracy, repeatability, and stability all reached the standards (RSD ≤ 5%); The recoveries ranged from 98% to 102% and RSDs were below 3%; The analysis results showed that the quality of the most batches was stable, tanshinone I, cryptotanshinone, dihydrotanshinone I, and tanshinon Ⅱ_A had a great influence on the quality of the drug, which could be monitored to ensure the quality of different batches. Conclusion The methods established in this paper have a high sensitivity and accuracy; the results of the methodology conform to the relevant requirements and the methods can rapidly determinate the multiple active components in DTSC; The research also provides a new scientific basis and reference for the quality assessment at the same time.

河南省高等学校重点科研项目资助（19A320070）；常州四药临床药学科研基金资助（CZSYJJ6015）；河南省科技计划项目资助（182102310243）