Prediction of allergic reaction risk of Shenmai injection based on real‐world evidence coupled with UPLC–Q‐TOF‐MS

The allergic reaction (AR) of Chinese herbal injection (CHI) has become one of the most noticeable focuses of public health in China. However, it still remains a considerable controversy as to whether low-molecular-weight components in CHI have potential sensitization. In this study, the relationship between AR and low-molecular-weight component profile of Shenmai injection was explored by an interdisciplinary technology integrating real-world evidence and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectroscopy (UPLC-Q-TOF-MS). The AR information of hospitalized patients was obtained by comprehensively analyzing real-world evidence from January 2015 to June 2019 at two Chinese hospitals. The UPLC-Q-TOF-MS was exploited to systematically investigate the low-molecular-weight component profile with 50-1500 m/z mass range, and 3725 MS1 peaks were detected. The optimized partial least squares discriminant analysis model was established to map the influence of low-molecular-weight components on AR. The results of this study showed that high levels of organic acids administered intravenously might be a potential risk factor for inducing AR. By using this method, Shenmai injection with high AR risk could be recognized precisely with 100% accuracy before clinical use.