Qi She Pill (QSP) is a traditional Chinese medicine (TCM) prescription that has been used in treating cervical spondylosis radiculopathy for many years. In this study, a simple and sensitive method using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC MS/MS) on a reverse-phase C18 column was developed for the simultaneous determination of the 19 major components in QSP. We found that the optimum mobile phase for gradient elution was 0.1% formic acid and methanol. The correlation coefficients of all calibration curves were greater than 0.99. Recoveries measured at three concentration levels varied from 95.43% to 102.35%. Relative standard deviations of intra- and inter-day precisions were less than 4.45%. After successfully validating our method, we then applied it to the quantification of 19 components in QSP products to show that this method provides a new standard in quality assessment of TCM prescriptions containing multiple bioactive components. (C) 2014 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.