Objective: To develop a high-performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS） method to comprehensively monitor and control the feeding of raw medicinal materials（Radix isatidis and Folium isatidis） in compound R. isatidis granules and to determinate the content of（R

S）-goitrin and indirubin. Methods: An Inertsil ODS-3 column（2.1×150 mm × 5 μm）（column temperature: 40 °C） was used for isocratic elution with a mobile phase of methanol ～ 0.05% formic acid（15:85）. Active ingredients were separated by HPLC.The determination was performed using the electrospray ionization source in positive ion mode; multiple reaction monitoring was selected for qualitative monitoring of the feeding of raw medicinal materials

and active ingredients were quantitatively analyzed. Results: Analysis of the common characteristic peaks of test article with reference herb and reference substance on the primary mass spectrum indicated that the feeding for the test article was based on the formula process. The content of（R

S）-goitrin and indirubin in 8 batches was calculated by determining the chromatographic peak areas of the two active ingredients.（R

S）-goitrin and indirubin showed a good linear relationship within the ranges of 1.07 ～ 21.48 μg/mL（r = 0.999 4） and 1.032 ～ 20.64 μg/mL（r = 0.999 5）

respectively;the relative standard deviations of precision experiments were 0.7% and 0.5%

respectively; the average recovery rates were 92.04% and 90.49%

respectively. Conclusion: The method is simple

convenient

accurate

reliable

and highly sensitive

which makes it suitable for comprehensive monitoring and control of the feeding and quality of raw medicinal materials（R. isatidis and F. isatidis） in compound R. isatidis granules.