OBJECTIVE ：To est ablish the method for the determination of 20（S）-protopanaxadiol（PPD）concentration in human plasma. METHODS ：Plasma samples were precipitated with acetonitrile and determined by UPLC-MS/MS ，using finandrogen as internal standard. The determination was performed on Waters ACQUITY UPLC HSS T 3 column with mobile phase consisted of 5 mmol/L ammonium bicarbonate aqueous solution-acetonitrile （gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The ion source was electrospray ion source，and negative ion scanning was carried out with multiple reaction monitoring mode . The ion pairs used for quantitative analysis were m/z 459.40→ 375.20（PPD）and m/z 371.30→315.30（internal standard ）. At the same time ，the method was applied to the determination of clinical samples. RESULTS ：The linear range of PPD was 0.25-30.00 ng/mL（r＝0.999 2），and the limit of quantitation was 0.25 ng/mL. RSDs of intra-batch and inter-batch were all lower than 10％，and relative errors （RE）were －14.61％-12.69％. Extraction method and matrix effect did not affect the quantitative determination of PPD. In ginsenoside CK 100 mg group ，ginsenoside CK 200 mg group and ginsenoside CK 300 mg group ，mean cmax of patients with rheumatoid arthritis after oral administration of corresponding drugs were 18.06，30.03，27.00 ng/mL；median tmax were 12.0，6.0，12.0 h；mean AUC 0-t were 622.52，668.15， 1 155.97 ng·h/mL. CONCLUTIONS ：The method for the determination of PPD concentration in human plasma is successfully established. The method is sensitive ，accurate， kq1907011） stable，easy to operate and less plasma consumption. It can be used for the quantitative determination of clinical samples.