A total of 36 male BALB/c athymic nude mice were randomly divided into two groups (18 for each group) for ST-A and ST-B. The mice were fasted for 12 h, then orally administered with Sor-Tos at a dose 27.5 mg kg−1. Blood was collected from the orbital sinus with a heparinized syringe at 0.5, 1, 2, 3, 4, and 8 h post drug administration. Blood was first centrifuged at 8000 rpm for 5 min, and 0.16 mL of the plasma was extracted. Then trifluoroacetic acid was used to precipitate protein, and NaOH was used to neutralize the solution. The mixture was diluted using ACN:H2O (7:3). After 10 min of precipitation, supernatant fluids were collected by centrifugation at 8000 rpm for 5 min, filtered with a syringe through a 0.45 μm hydrophilic membrane filter, and analyzed by the HPLC method. The experimental details are described in Supplementary Materials.

Interventional studies involving mice were performed in accordance with the China Animal Protection Law and were approved by the Zhejiang University Institutional Animal Care and Use Committee, China (approval ID ZJU20190018).

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