UPLC-MS/MS法测定冠心舒通胶囊中多种活性成分的含量及药物质量评价

Quantitative analysis of multiple active components and quality evaluation research in Guanxinshutong capsules based on UPLC-MS/MS

目的建立同时测定冠心舒通胶囊中11种活性成分含量的UPLC-MS/MS分析方法,并采用主成分分析技术综合评价其药物质量。方法采用UPLC-MS/MS法分析检测,色谱柱为Acquity UPLCBEH C_(18)(50 mm×2.1 mm,1.8μm)柱,流动相为乙腈-体积分数0.1%甲酸水,梯度洗脱,流速为0.2 m L·min^(-1);ESI正、负离子同时采集,除熊果酸为选择离子监测(selected ion monitor,SIR)外,其余10种成分均为多反应监测(multiple reaction monitoring,MRM);多批次冠心舒通胶囊含量测定结果采用多元数据处理软件SIMCA14.0进行主成分分析,并评价其质量。结果在优化的色谱质谱条件下,丹参素、原儿茶酸、原儿茶醛、咖啡酸、迷迭香酸、丹酚酸B、丹酚酸A、丹参酮I、隐丹参酮、丹参酮IIA和熊果酸分别在质量浓度10.0~100.0 mg·L^(-1)、45.0~450.0 mg·L^(-1)、3.0~30.0 mg·L^(-1)、1.0~10.0 mg·L^(-1)、9.0~90.0 mg·L^(-1)、100.0~1 000.0 mg·L^(-1)、10.0~100.0 mg·L^(-1)、10.0~100.0 mg·L^(-1)、25.0~250.0 mg·L^(-1)、9.0~90.0 mg·L^(-1)和3.0~30.0 mg·L^(-1)内呈良好线性关系(r≥0.999 6);加样回收率为98%~101%;10批冠心舒通胶囊平均含量分别为1.269、2.708、0.359、0.141、1.125、14.951、0.664、0.787、2.489、0.681和0.249 mg·g^(-1)。结论作者建立的UPLC-MS/MS法可用于冠心舒通胶囊中多种主要活性成分的快速测定;含量测定结果表明不同批次冠心舒通胶囊总体质量较为稳定,结果分析使用的主成分分析法可从整体上综合评价药物质量,为冠心舒通胶囊的质量控制研究提供新的科学依据和数据处理方法。

Objective To establish a rapid MS method for the determination of eleven principal active components in Guanxinshutong capsules and make a comprehensive evaluation of the quality of drugs by principal component analysis technology. Methods The UPLC-MS/MS method was used and the chromato- graphic conditions were as follows： the column was ACQUITY UPLC BEH CIs （50 mm x 2. 1 nun, 1.8 txm）, the mobile phase was consisted of acetonitrile-water （containing 0. 1% formic acid） at a flow rate of 0. 2 mL. min-1 with gradient elution; Mass spectrometer conditions： A triple quadrupole mass spectrometer equipped with electrospray ionization source （ESI） was used in positive and negative ion mode, and multiple reaction monitoring （MRM） was performed except ursolic acid in selected ion recording （SIR） for quantitative analysis of these compounds;The results of the determinations were calculated by principal component analysis of multivariate data processing software SIMCA14.0 to evaluate the quality. Results Under the optimized conditions, danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, rosmarinic, salvianolic acid B, salvianolic acid A, tanshinone I, cryptotanshinone, tanshinone IIA and ursolic acid all showed good liners in the range of 10. 0-100. 0 mg·L^-1, 45.0-450. 0 mg·L^-1, 3.0- 30. 0 mg·L^-1 ,1.0-10. 0 mg·L^-1 ,9. 0-90. 0 mg·L^-1, 100. 0-1000. 0 mg·L^-1 , 10. 0-100. 0 mg ·L^-1 , 10.0- 100. 0 mg ·L^-1 , 25.0-250. 0 mg·L^-1 , 9.0-90. 0 mg·L^-1 and 3.0-30. 0 mg·L^-1 , respectively （ r≥ 0.999 6）. The recoveries were ranged from 98%-101%. The average contents in the ten batches of Guanxinshutongcapsules were 1.269 mg·L^-1,2.708 mg·L^-1,0.359 mg·L^-1,0.141 mg ·L^-1, 1. 125 mg·L^-1,14. 951 mg ·L^-1,0. 664 mg ·L^-1,0. 787 mg ·L^-1, 2. 489 mg ·L^-1,0. 681 mg·L^-1 and 0. 249 mg·L^-1, respectively. Conclusions The results showed that the UPLC-MS/MS method could be used for the rapid determination of a variety of main active components in the Guanxinshutong capsules; The results showed that the quality was stable in the different batches and displayed a overall comprehensive e- valuation of the drug quality by using the principal component analysis method, it also provides a scientific basis and data processing method for the quality control of this drug.