The measurement of critical quality attributes of Tongren niuhuang qingxin pills based on MIF-HEMT biosensor technology

Chao-fu MA; Zi-jian Wang; Li-juan MA; Xiao-yan HU; Yu-nan Wei; Xiao-meng Zhang; Xin-yu Guo; Xing-yue Huan; Jing Zhao; Jin-fan XU; Nan LI; Zhi-bin Wang; Jing DU; Zhi-sheng WU

Return

The measurement of critical quality attributes of Tongren niuhuang qingxin pills based on MIF-HEMT biosensor technology

VernacularTitle:基于MIF-HEMT生物传感技术的同仁牛黄清心丸关键质量属性测量研究
Author: Chao-fu MA ^{1
,

2} ; Zi-jian WANG ³ ; Li-juan MA ^{1
,

2} ; Xiao-yan HU ^{1
,

2} ; Yu-nan WEI ^{1
,

2} ; Xiao-meng ZHANG ^{1
,

2} ; Xin-yu GUO ^{1
,

2} ; Xing-yue HUAN ^{1
,

2} ; Jing ZHAO ^{1
,

2} ; Jin-fan XU ^{1
,

2} ; Nan LI ^{1
,

2} ; Zhi-bin WANG ³ ; Jing DU ⁴ ; Zhi-sheng WU ^{1
,

2}
Author Information

1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
2. Engineering Research Center of Chinese Medicine Production and New Drug Development, Beijing 102488, China
3. Beijing Tongrentang Technology Development Co., Ltd., Beijing 100079, China
4. Beijing Tongrentang Co., Ltd., Beijing 100031, China
Publication Type:Research Article
Keywords: macrophage migration inhibitory factor; high electron mobility transistor; biosensor; Tongren niuhuang qingxin pill; critical quality attribute
From: Acta Pharmaceutica Sinica 2023;58(10):2853-2861
CountryChina
Language:Chinese
Abstract: There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the K_D of which reached to 8.722×10^-10 g·mL^-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.