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Adding 150 µL of methanol to 50 µL of the plasma sample for protein precipitation, the mixture was vortexed for 10 min and then centrifuged at 13,200 rpm for 15 min at 4°C. Then, 100 µL of the supernatant was transferred to a polypropylene tube and evaporated until completely drying under a vacuum. The residue was reconstituted with 200 µL of methanol. After vortexing for 5 min, 100 µL of the upper layer was transferred to a vial for analysis.

Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 6 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 7 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 8 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 9 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 10 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 11 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 12 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 13 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 14 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 15 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 16 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 17 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 18 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 19 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 20 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 21 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 22 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 23 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 24 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 25 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 26 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 27 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 28 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 29 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 30 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 31 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 32 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 33 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 34 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 35 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 36 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 37 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 38 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 39 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 40 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 41 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 42 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 43 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 44 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 45 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 46 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 47 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 48 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 49 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 50 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 51 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 52 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 53 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 54 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 55 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 56 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 57 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 58 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 59 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 60 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 61 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 62 µL. , Ultra-high-performance liquid chromatography (UHPLC) was performed using an UltiMate™ 3000 Series (Dionex Corp., Thermo Scientific, Sunnyvale, CA, USA). The UHPLC column was a 2.1 × 100 mm, 1.7 µm, ACQUITYTM UPLC BEH C18 (Waters, Milford, MA, USA). The column oven and autosampler were maintained at 40°C and 10°C, respectively. The mobile phase was distilled water containing 0.1% formic acid (solvent A) or acetonitrile containing 0.1% formic acid (solvent B). The mobile phase was delivered at a flow rate of 0.35 mL/min using a gradient program as follows: 0–1.5 min, 5% B; 1.5–5.0 min, 5%–85% B; 5.0–24.0 min, 85%–95% B; 24.0–26.0 min 95% B; 26.0–26.5 min, 95%–5% B; 26.5–30.0 min, 5% B. The injection volume of the sample was 63 µL.

Metabolic profiling was conducted using a Bruker CompactTM QTOF/MS (Bruker Daltonics GmbH & Co., KG, Bremen, Germany) equipped with an electrospray ionization interface source