Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale finger-printing method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM tech-nique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.