目的 基于UHPLC-ESI-HRMSⁿ建立一种快速定量检测清热灵颗粒中甘草苷、牡荆苷、黄芩苷、芦丁、隐绿原酸、绿原酸、槲皮素、山柰酚的分析方法，为清热灵颗粒的质量控制提供实验基础。方法 采用BEH C₁₈（100 mm×2.1 mm，1.7 μm）色谱柱，以甲醇-0.1%甲酸水溶液为流动相梯度洗脱，体积流量0.3 mL/min；质谱采用ESI离子源，全扫描模式进行检测；多批次清热灵颗粒定量测定结果采用SIMCA14.1软件进行模式判别分析，评估其质量。结果 甘草苷、黄芩苷、芦丁、牡荆苷、槲皮素、绿原酸、隐绿原酸、山柰酚分别在570~9 127、10 032~160 500、293~4 690、1 625~26 000、40.5~645、41~1 325、44~1 413、13~209 ng/mL线性关系良好（r ≥ 0.999 0）；精密度、重复性、稳定性良好；加样回收率在98.83%~100.65%，RSD值均小于3%。5批所测清热灵颗粒中甘草苷、黄芩苷、芦丁、牡荆苷、槲皮素、绿原酸、隐绿原酸、山柰酚的平均质量分数分别为202.07~438.15、10 258.03~11 046.56、56.09~87.75、689.19~818.56、4.95~6.07、8.87~18.37、22.49~42.12、3.21~4.11 μg/g；定量数据经SIMCA 14.1分析表明，5批清热灵颗粒质量标准偏差均在±2范围内。结论 建立的定量测定方法简单快速，灵敏度度高，准确度好；方法学考察结果符合测定要求；可以作为清热灵颗粒多种活性成分定量方法，为其质量控制提供新的依据。

Objective To establish a quantitative analysis method of multiple active components liquiritin, vitexin, baicalin, rutin, cryptochlorogenic acid, chlorogenic acid, quercetin, and kaempferol in Qingreling Granules (QG) based on UHPLC-ESI-HRMSⁿ, in order to provide a comprehensive evaluation for the quality control of QG. Methods The chromatographic separation was carried on BEH C₁₈ (100 mm×2.1 mm, 1.7 μm) column with methanol-0.1% formic acid water as mobile phase at the flow rate of 0.3 mL/min. Full scan mode with an electrospray ionization (ESI) source was used for the detection. The quantitative determination results were calculated by the pattern recognition function of the software SIMCA 14.1 to evaluate the quality of QG. Results Liquiritin, baicalin, rutin, vitexin, quercetin, chlorogenic acid, cryptochlorogenic acid, and kaempferol all showed good liners relationship (r ≥ 0.999 0) in the ranges of 570-9 127, 10 032-160 500, 293-4 690, 1 625-26 000, 40.5-645, 41-1 325, 44-1 413, and 13-209 ng/mL, respectively. The precision, repeatability, and stability were all up to the standards. The recoveries of standard addition was 98.83% to 100.65% with precision of below 3% RSD (n=5). The average mass fractions of liquiritin, baicalin, rutin, vitexin, quercetin, chlorogenic acid, cryptochlorogenic acid, and kaempferol in five batches of QG were 202.07-438.15, 10 258.03-11 046.56, 56.09-87.7, 689.19-818.56, 4.95-6.0, 8.87-18.37, 22.49-42.12, 3.21-4.11 μg/g, respectively. The data analyzed by SIMCA 14.1 showed that the quality deviation of five batches of QG were within ±2. Conclusion The method established in this study is simple, rapid, sensitive and accurate. The results of methodology conform to the relevant requirements and the method can be used as a quantitative method for the active ingredients in QG. The research also provides a new basis for the quality control at the same time.

国家重点研发计划（2017YFC1700705）；国家留学基金委资助项目（CSC201500850007）；四川省科技厅科技支撑计划（2014SZ0131）；四川省基础研究重点项目（2018JY0069）；西南民族大学2018中央高校重点项目（2018NZD18）