Table 2.
Metabolites identified in plasma of rats after oral administration by UPLC/Q-TOF MS.
| No. | Parent compounds | Metabolic pathways | Formula | tR (min) | [M+H]+ (m/z) | Error (ppm) | Product ions | |
|---|---|---|---|---|---|---|---|---|
| Calculated | Measure | |||||||
| 1 | 4,7-Dihydroxy-3-butylphthalide, senkyunolide D | Prototype | C12H14O4 | 9.75 | 223.0965 | 223.0963 | −1 | 177.0899, 167.0387, 149.0226, 121.0278, 91.0541 |
| 2 | 4,7-Dihydroxy-3-butylphthalide, senkyunolide D | Hydroxyl and methyl conjugation | C13H16O5 | 10.78 | 253.1071 | 253.1071 | 0.2 | 235.0963, 221.0829, 202.0596, 193.0489, 179.0332, 175.0379, 150.0301, 121.0268 |
| 3 | 4,7-Dihydroxy-3-butylphthalide, senkyunolide D | Sulfate conjugation | C12H14SO7 | 9.2 | 303.0533 | 303.0535 | 0.5 | 285.0430, 205.0858, 187.0753, 177.0904, 149.0244, 121.0283, 91.0534 |
| 4 | 4,7-Dihydroxy-3-butylphthalide, senkyunolide D | Glucuronide conjugation | C18H22O10 | 10.6 | 399.1286 | 399.1285 | −0.3 | 223.0969, 205.0847, 177.0883, 167.0331, 149.0233, 121.0315 |
| 5 | 4,7-Dihydroxy-3-butylphthalide, senkyunolide D | Hydrogenation and glucuronide conjugation | C18H24O10 | 8.67 | 401.1442 | 401.1444 | 0.3 | 225.4427, 207.1017, 189.0924, 172.0884, 165.0548, 141.0170, 119.0851, 113.0288 |
| 6 | 4,7-Dihydroxy-3-butylphthalide, senkyunolide D | Hydroxyl and glucuronide conjugation | C18H22O11 | 8.92 | 415.1235 | 415.1238 | 0.7 | 227.0584, 221.0824, 167.0331 |
| 7 | 3-Butyl-3-hydroxy-4,5,6,7-tetrahy-dro-6,7-dihydroxyphthalide | Prototype | C12H18O5 | 7.76 | 243.1227 | 243.1225 | −0.7 | 165.0909, 151.0414, 137.0951, 123.0431, 107.0499, 91.0546, 85.0648 |
| 8 | 3-Butyl-3-hydroxy-4,5,6,7-tetrahy-dro-6,7-dihydroxyphthalide | Methyl conjugation | C13H20O5 | 10.01 | 257.1384 | 257.1381 | −1 | 221.1211, 207.0993, 165.0913, 137.0951, 123.0434 |
| 9 | 3-Butyl-3-hydroxy-4,5,6,7-tetrahy-dro-6,7-dihydroxyphthalide | Cystein conjugation | C15H23O6NS | 7.67 | 346.1319 | 346.1319 | 0 | 328.1222, 310.1111, 264.1056, 238.0916, 223.0771, 207.1018, 165.0923, 137.0955 |
| 10 | 3-Butyl-3-hydroxy-4,5,6,7-tetrahy-dro-6,7-dihydroxyphthalide | Oxidation and cystein conjugation | C15H23O7NS | 9.47 | 362.1268 | 362.1267 | −0.3 | 327.0911, 247.1337, 229.1216, 151.0746 |
| 11 | 3-Butyl-3-hydroxy-4,5,6,7-tetrahy-dro-6,7-dihydroxyphthalide | N-Acetyl-L-cysteine conjugation | C17H25O8NS | 5.97 | 404.1374 | 404.1372 | −0.5 | 205.0833, 171.1364 |
| 12 | 3-Butyl-3-hydroxy-4,5,6,7-tetrahy-dro-6,7-dihydroxyphthalide | Desat and S-GSH conjugation | C22H33O11N3S | 4.39 | 548.1909 | 548.1921 | 2.3 | 473.1636, 419.1465, 205.0860 |
| 13 | 3-Butyl-3-hydroxy-4,5,6,7-tetrahy-dro-6,7-dihydroxyphthalide | H2O conjugation | C12H20O6 | 4.65 | 261.1333 | 261.1320 | −4.6 | 261.1310 |
| 14 | 3-Carboxyethyl-phthalide | Prototype | C10H8O4 | 7.28 | 193.0495 | 193.0490 | −2.7 | 178.0257, 150.0323, 133.0277, 122.0361, 105.0338, 77.0388 |
| 15 | 3-Carboxyethyl-phthalide | Methyl conjugation | C11H10O4 | 11.52 | 207.0652 | 207.0646 | −3 | 147.0441, 131.0502, 103.0546, 91.0533 |
| 16 | 3-Carboxyethyl-phthalide | Glucuronide conjugation | C16H16O10 | 5.51 | 369.0816 | 369.0822 | 1.5 | 193.0493 |
| 17 | 3-Carboxyethyl-phthalide | Hydroxyl and glucuronide conjugation | C16H16O11 | 5.72 | 385.0765 | 385.0758 | −2.1 | 209.0455 |
| 18 | 3-Carboxyethyl-phthalide | Hydrogenation | C10H10O4 | 7.64 | 195.0652 | 195.0651 | −0.6 | 177.0547, 149.0609, 145.0276, 134.0354, 117.0309, 89.0395 |
| 19 | Cnidilide, neocnilide | Prototype | C12H18O2 | 16.14 | 195.1380 | 195.1377 | −1.5 | 177.1350, 149.1348, 125.0599, 107.0873, 97.0640, 91.0550, 79.0543 |
| 20 | Cnidilide, neocnilide | Methyl conjugation | C13H20O2 | 15.63 | 209.1536 | 209.1537 | 0.4 | 193.0211, 167.1088, 153.0917, 121.0648, 68.9961 |
| 21 | Cnidilide, neocnilide | Acetyl conjugation | C14H20O3 | 12.45 | 237.1485 | 237.1483 | −1.1 | 177.0257 |
| 22 | Cnidilide, neocnilide | Hydroxyl and acetyl conjugation | C14H20O4 | 12.46 | 253.1434 | 253.1435 | 0.4 | 235.1340, 193.0856, 157.1012, 135.0816 |
| 23 | Cnidilide, neocnilide | Oxidation and cystein conjugation | C15H23O4NS | 10.07 | 314.1421 | 314.1424 | 1.1 | 268.1343, 193.1185 |
| 24 | Cnidilide, neocnilide | Hydroxyl and glucuronide conjugation | C18H26O9 | 9.62 | 387.1650 | 387.1650 | 0.1 | 211.1330, 193.1223, 175.1129, 147.1168, 121.0368 |
| 25 | Cnidilide, neocnilide | 2Hydroxyl and glucuronide conjugation | C18H26O10 | 8.02 | 403.1599 | 403.1598 | −0.2 | 227.1287, 209.1174, 191.1065, 171.1373, 163.1123, 153.0549, 145.1025, 141.0186, 135.1164, 121.0995 |
| 26 | Cnidilide, neocnilide | 2Hydroxyl conjugation | C12H18O4 | 8.68 | 227.1278 | 227.1279 | 0.7 | 191.1057, 163.1115, 153.0554, 145.1001, 135.0444, 105.0705, 91.0541 |
| 27 | Senkyunolide A | Prototype | C12H16O2 | 14.81 | 193.1223 | 193.1222 | −0.5 | 175.1118, 147.1170, 137.0580, 119.0848, 105.0710, 91.0556, 77.0393 |
| 28 | Senkyunolide A | Hydroxyl and methyl conjugation | C13H18O3 | 15.85 | 223.1329 | 223.1326 | −1.2 | 205.1224, 191.1060, 149.0235, 135.0429, 121.0279, 105.0697, 91.0542, 77.0397 |
| 29 | Senkyunolide A | Hydroxyl and acetylcysteine conjugation | C17H25O6NS | 10.35 | 372.1475 | 372.1475 | −0.1 | 330.1375, 284.1322, 267.1048.239.0756, 209.1169, 191.1074, 162.0210, 153.0540, 130.0492 |
| 30 | Senkyunolide A | Carboxyl and glucuronide conjugation | C18H22O10 | 10.6 | 399.1286 | 399.1285 | −0.3 | 223.0969, 205.0847, 177.0883, 159.0293, 149.0233, 131.0840, 85.0275 |
| 31 | Senkyunolide A | 2Hydroxyl and glucuronide conjugation | C18H24O10 | 8.67 | 401.1442 | 401.1444 | 0.3 | 225.1127, 207.1017, 189.0924, 172.0884, 165.0548, 141.0170, 119.0851, 113.0288, 85.0265, 73.0295 |
| 32 | Senkyunolide A | H2O conjugation | C12H18O3 | 10.54 | 211.1329 | 211.1327 | −0.9 | 193.1225, 175.1096, 147.1156, 129.0700, 105.0693, 93.0692, 79.0548 |
| 33 | Senkyunolide A | 2Hydroxyl conjugation | C12H16O4 | 9.56 | 225.1121 | 225.1119 | −1 | 207.1013, 189.0914, 165.0537, 133.0637, 105.0706, 91.0536, 81.0713 |
| 34 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Prototype | C12H16O3 | 12.79 | 209.1172 | 209.1173 | 0.3 | 153.0686, 149.0594, 145.0984, 135.0472, 105.0693, 91.0562, 77.0409 |
| 35 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Methyl conjugation | C13H18O3 | 15.85 | 223.1329 | 223.1326 | −1.2 | 191.1060, 173.0946, 149.0235, 145.1014, 135.0429, 105.0697, 91.0542, 79.0551 |
| 36 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Acetyl conjugation | C14H18O4 | 15.99 | 251.1278 | 251.1276 | −0.6 | 177.1261, 149.0593, 69.0014, 57.0752 |
| 37 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Hydroxyl and acetyl conjugation | C14H18O5 | 12.27 | 267.1227 | 267.1226 | −0.4 | 249.1137, 193.0479, 189.0582, 135.0435, 119.0846 |
| 38 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Taurine conjugation | C15H21O5NS | 9.02 | 328.1213 | 328.1214 | 0.1 | 207.1015, 189.0911, 165.0541, 161.0955, 147.0814, 133.0644, 119.0859, 91.0538 |
| 39 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | N-Acetyl-L-cysteine conjugation | C17H23O6NS | 11.15 | 370.1319 | 370.1320 | 0.3 | 282.1162, 264.1083, 207.1015, 189.0911, 165.0544, 147.0785, 133.0652, 119.0858, 91.0546 |
| 40 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Hydrogenation and glucuronide conjugation | C18H26O9 | 9.62 | 387.1650 | 387.1650 | 0.1 | 211.1330, 193.1223, 175.1129, 147.1168, 121.0638, 91.0546, 79.0562 |
| 41 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Hydroxyl and acetylcysteine conjugation | C17H25O7NS | 8.29 | 388.1425 | 388.1422 | −0.6 | 207.1010, 164.0390, 122.0273, 105.0347, 79.0529 |
| 42 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Hydroxyl and glucuronide conjugation | C18H24O10 | 8.67 | 401.1442 | 401.1444 | 0.3 | 267.1015, 225.1127, 207.1017, 189.0924, 172.0844, 141.0170, 113.0228, 85.0265, 73.0295 |
| 43 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Carboxyl and glucuronide conjugation | C18H22O11 | 8.92 | 415.1235 | 415.1238 | 0.7 | 227.0584, 221.0824 |
| 44 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Desat and S-GSH conjugation | C22H31O9N3S | 9.17 | 514.1854 | 514.1854 | 0 | 439.1552, 385.1429, 282.1160, 207.1017, 189.0921, 179.0484, 162.0221, 144.0103, 116.0174, 76.0218 |
| 45 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | S-GSH conjugation | C22H33O9N3S | 8.61 | 516.2010 | 516.2010 | −0.1 | 441.1694, 387.1593, 284.1315, 209.1173, 191.1055, 162.0212, 144.0109, 116.0175, 84.0447 |
| 46 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Hydrogenation | C12H18O3 | 10.54 | 211.1329 | 211.1327 | −0.9 | 193.1225, 175.1096, 151.0737, 147.1156, 129.0700, 121.0641, 105.0693, 93.0693, 91.0546, 77.0398 |
| 47 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Hydroxyl and demethyl conjugation | C12H14O4 | 9.75 | 223.0965 | 223.0963 | −1 | 177.0906, 149.0590, 145.0980, 105.0329, 91.0556, 77.0394 |
| 48 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | H2O conjugation | C12H18O4 | 8.68 | 227.1278 | 227.1279 | 0.7 | 209.1169, 191.1057, 163.1115, 153.0554, 145.1001, 135.0444, 105.0705, 91.0541, 77.0388, 65.0402, 55.0198 |
| 49 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Demethyl and carboxyl conjugation | C12H14O5 | 9.79 | 239.0914 | 239.0915 | 0.4 | 221.0816, 193.0885, 179.0336, 165.0173, 161.0227, 128.0633, 109.0292, 77.0376 |
| 50 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | 2hydrogenation and 2hydroxyl conjugation | C12H18O5 | 7.76 | 243.1227 | 243.1225 | −0.7 | 225.1135, 207.1017, 179.1084, 165.0909, 151.0414, 137.0951, 123.0431, 95.0486 |
| 51 | Senkyunolide G, senkyunolide K,Z-6,7-epoxyligustilide | Aromatic hydrocarbon oxidation | C13H18O5 | 11.38 | 255.1227 | 255.1222 | −2.1 | 195.1024, 135.0798, 131.0870 |
| 52 | Senkyunolide J,N,R2 | Prototype | C12H18O4 | 8.68 | 227.1278 | 227.1279 | 0.7 | 163.1115, 153.0554, 145.1001, 107.0705, 91.0541, 79.0544, 65.0402, 55.0198 |
| 53 | Senkyunolide J,N,R2 | Methyl conjugation | C13H20O4 | 11.42 | 241.1434 | 241.1433 | −0.6 | 209.1147, 191.1067, 163.1089, 153.0559, 121.0652, 93.0717, 85.0663, 79.0663, 57.0698 |
| 54 | Senkyunolide J,N,R2 | Hydroxyl and methyl conjugation | C13H20O5 | 10.01 | 257.1384 | 257.1381 | −1 | 221.1211, 207.0993, 165.0913, 161.0984, 137.0951, 123.0434, 93.0699, 79.0549, 67.0538 |
| 55 | Senkyunolide J,N,R2 | Glycine conjugation | C14H21O5N | 7.49 | 284.1493 | 284.1495 | 0.8 | 238.1464, 209.1195, 191.1065, 163.1151, 153.0546, 135.1157, 117.0704, 91.0562, 76.0410, 57.0711 |
| 56 | Senkyunolide J,N,R2 | Cystein conjugation | C15H23O5NS | 8.48 | 330.1370 | 330.1375 | 1.7 | 284.1324, 209.1176, 191.1066, 163.1120, 153.0544, 145.1015, 121.1008, 93.0695, 85.0650 |
| 57 | Senkyunolide J,N,R2 | Taurine conjugation | C14H23O6NS | 7.56 | 334.1319 | 334.1319 | 0 | 209.1147, 181.1211, 153.0555, 126.0211, 108.0102, 91.0549 |
| 58 | Senkyunolide J,N,R2 | Oxidation and cystein conjugation | C15H23O6NS | 7.67 | 346.1319 | 346.1319 | 0 | 328.1222, 310.1111, 264.1056, 238.0916, 207.1018, 195.0853, 165.0923, 137.0955 |
| 59 | Senkyunolide J,N,R2 | N-Acetyl-L-cysteine conjugation | C17H25O7NS | 8.29 | 388.1425 | 388.1422 | −0.6 | 207.1010, 164.0390, 107.0491, 122.0273, 105.0347 |
| 60 | Senkyunolide J,N,R2 | Glucuronide conjugation | C18H26O10 | 8.02 | 403.1599 | 403.1598 | −0.2 | 227.1287, 209.1174, 191.1065, 163.1123, 153.0549, 145.1025, 135.1164, 121.0995, 93.0712 |
| 61 | Senkyunolide J,N,R2 | S-GSH conjugation | C22H35O10N3S | 4.96 | 534.2116 | 534.2113 | −0.6 | 459.1795, 405.1696, 387.1582, 369.1490, 341.1469, 302.1438, 284.1303, 284.1303, 241.0913, 209.1157, 191.1075 |