To investigate the metabolites and metabolic pathways of WJ-14, a novel anti-depressant compound, in rats and human liver microsomes by HPLC-MS/MS.
Samples of rat plasma and urine, as well as in vitro incubation system of human liver microsomes were analyzed by HPLC-MS/MS. Chromatographic conditions: the chromatographic conditions were as follows: Hypersil BDS C18 (100 mm×4.6 mm, 3 μm) column, with 0.1% formic acid aqueous solution (A)-methanol (B) as the mobile phase, gradient elution flow rate 0.4 mL·min-1, column temperature 40 ℃, and injection volume 5 μL. The identification of metabolites and speculation on the metabolic pathways of WJ-14 were conducted by comparing the fragmentation mode and characteristic fragment ions of WJ-14.
A total of 12 metabolites of WJ-14 were identified, including 6 in rat and 6 in human liver microsomes, with two metabolites were detected in both rat and human liver microsomes. The major metabolic pathways of WJ-14 were identified as hydroxylation, demethylation, hydration, glucuronidation and methylation.
In this work, we investigated the metabolites and metabolic pathways of WJ-14 using HPLC-MS/MS for the first time. The metabolism of WJ-14 occurred in phase Ⅰ and phase Ⅱ metabolic reactions, in which hydroxylation in phase Ⅰ is dominant. The results of the current study may provide valuable information for the formulation development and application of WJ-14.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |