TABLE 2

Detection of major metabolites of tanshinol (6), protocatechuic aldehyde (1), rosmarinic acid (10), salvianolic acid A (16), salvianolic acid D (13), and lithospermic acid (22) in human plasma and/or urine samples collected during and after an intravenous infusion dose of DanHong injection

ID^{^a}	Parent compound/metabolite	LC/TOF-MS^E Data			Molecular Mass	Molecular Formula
ID^{^a}	Parent compound/metabolite	t_R	[M−H]⁻ (m/z)	Fragmentation profile^{^b} (m/z)	Molecular Mass	Molecular Formula
		min			Da
Metabolites of tanshinol (6)
6	Tanshinol	6.61	197.0455	179.0346,^{^b} 135.0454, 123.0453	198.0528	C₉H₁₀O₅
M6_M	Methyltanshinol	9.90	211.0611	193.0507, 150.0323,^{^b} 134.0371	212.0684	C₁₀H₁₂O₅
Metabolites of protocatechuic aldehyde (1)
1	Protocatechuic aldehyde	8.36	137.0240	109.0311, 108.0233^{^b}	138.0317	C₇H₆O₃
2	Protocatechuic acid	7.07	153.0194	109.0295^{^b}	154.0266	C₇H₆O₄
M2_M	Methylprotocatechuic acid	10.8	167.0348	123.0451^{^b}	168.0422	C₈H₈O₄
M2_M-G-1	Methylprotocatechuic acid glucuronide	8.04	343.0660	167.0345,^{^b} 123.0443	344.0743	C₁₄H₁₆O₁₀
M2_M-G-2	Methylprotocatechuic acid glucuronide	8.96	343.0671	167.0351,^{^b} 123.0441	344.0743	C₁₄H₁₆O₁₀
M2_S-1	Protocatechuic acid sulfate	10.3	232.9767	153.0193,^{^b} 109.0291	233.9838	C₇H₆SO₇
M2_S-2	Protocatechuic acid sulfate	10.7	232.9759	153.0195,^{^b} 109.0295	233.9838	C₇H₆SO₇
Metabolites of rosmarinic acid (10)
10	Rosmarinic acid	16.70	359.0775	197.0453, 179.0345, 161.0242^{^b}	360.0845	C₁₈H₁₆O₈
M10_M-1	Methylrosmarinic acid	16.26	373.0918	197.0446, 175.0392,^{^b} 179.0346	374.1001	C₁₉H₁₈O₈
M10_M-2	Methylrosmarinic acid	18.18	373.0919	197.0452,175.0389, 135.0447^{^b}	374.1001	C₁₉H₁₈O₈
M10_2M	Dimethylrosmarinic acid	19.47	387.1078	211.0600,^{^b} 193.0492, 175.0388	388.1158	C₂₀H₂₀O₈
M10_2M-S-1	Dimethylrosmarinic acid sulfate	21.33	467.0649	387.1076, 211.0605,^{^b} 175.0392	468.0726	C₂₀H₂₀SO₁₁
M10_2M-S-2	Dimethylrosmarinic acid sulfate	21.44	467.0650	387.1085, 211.0601,^{^b} 175.0388	468.0726	C₂₀H₂₀SO₁₁
M10_2M-G-1	Dimethylrosmarinic acid glucuronide	17.17	563.1411	387.1085, 211.0606,^{^b} 193.0484	564.1479	C₂₆H₂₈O₁₄
M10_2M-G-2	Dimethylrosmarinic acid glucuronide	17.59	563.1405	387.1093, 211.0607, 193.0501^{^b}	564.1479	C₂₆H₂₈O₁₄
Metabolites of salvianolic acid A (16)
16	Salvianolic acid A	18.41	493.1127	313.0716, 295.0611,^{^b} 185.0246	494.1208	C₂₆H₂₂O₁₀
M16_M-G-1	Methylsalvianolic acid A glucuronide	18.62	683.1606	507.1295,335.0576,295.0599^{^b}	684.1690	C₃₃H₃₂O₁₆
M16_M-G-2	Methylsalvianolic acid A glucuronide	19.03	683.1611	507.1285,335.0553,295.0608^{^b}	684.1690	C₃₃H₃₂O₁₆
M16_M-G-3	Methylsalvianolic acid A glucuronide	19.46	683.1616	507.1293,335.0557,295.0608^{^b}	684.1690	C₃₃H₃₂O₁₆
M16_2M-G-2	Dimethylsalvianolic acid A glucuronide	19.76	697.1771	521.1448, 327.0865, 309.0767^{^b}	698.1847	C₃₄H₃₄O₁₆
Metabolites of salvianolic acid D (13)
13	Salvianolic acid D	16.30	417.0833	373.0917, 197.0447, 175.0393^{^b}	418.0900	C₂₀H₁₈O₁₀
M13_M	Methylsalvianolic acid D	17.79	431.0981	387.1073, 211.0608, 175.0392^{^b}	432.1056	C₂₁H₂₀O₁₀
Metabolites of lithospermic acid (22)
22	Lithospermic acid	16.75	537.1037	493.1141, 313.0725, 295.0625^{^b}	538.1111	C₂₇H₂₂O₁₂
M22_M	Methyllithospermic acid	18.00	551.1198	507.1316, 327.0869, 309.0774^{^b}	552.1268	C₂₈H₂₄O₁₂
M22_2M	Dimethyllithospermic acid	19.22	565.1342	521.1436, 327.0879, 309.0753^{^b}	566.1424	C₂₉H₂₆O₁₂

t_R, chromatographic retention time.
↵^a The metabolite ID contains a capital letter M and a number corresponding to compound ID, for instance, M6 in M6_M-S-1 denotes “metabolite of compound 6 (tanshinol)”; in the subscript, a letter denotes the reaction undergone by the compound (M denotes methylation; S, sulfation; G, glucuronidation) while a number such as “1” denotes “the first eluted isomer of the metabolite”.
↵^b Product ion of base peak.