Metabolism of gartanin in liver microsomes and its modulating effects on cytochrome P450s

Abstract

The retention time (11.20 min), [M-H] − and MS/MS spectra of the molecular ion at m/z 395.0658 (M0) were the same as those of the gartanin standard. Therefore, M0 was confirmed as the unchanged parent drug. Gartanin gave the characteristic fragment ions at m/z 351.0123, 339.0141, and 296.9763. The cleavage of gartanin at C-22 and C-17 produced a daughter ion at m/z 351, which created further fragment ions at m/z 339.0141. However, the structure of the fragment ion at m/z 296.9763 was not inferred. M1 and M2The molecular formulas of M1 (tR = 9.42 min) and M2 (tR = 10.21 min) were determined as C23H24O7 with the [M-H] − at m/z 411.0722 and 411.0719, respectively.Their m/z was 16 Da higher than that of gartanin, indicating that they were the hydroxylated metabolite of the parent drug. The hydroxyl group was added to the parent molecule at C-18(19) or C-22(23). Based on the MS/MS spectra of M1 and M2, two side chains underwent a series of cleavage at C-22, C-21, and C-17 and generated the product ion at m/z 381.0663, 351.0247, and 337.0116. The m/z 351 fragment was the same as gartanin, due to cleavage of the isoprenyl group, indicating the new