Figure 1.
Chromatograms of GC/TOFMS and LC-IT-TOFMS.
(A). Typical GC/TOFMS chromatograms of rat blood serum. (B). The LC-IT-TOF/MS-extracted ion chromatograms (EIC) of a bile sample from a rat treated with triptolide. P, parent drug; M1, GSH conjugate of triptolide; M2, mono-hydroxylated triptolide; M3–M6, dihydroxylated triptolide; M7, carboxylated triptolide; M8–M9, triptolide sulfate; M10, mono-hydroxylated triptolide coupled with GSH.
Figure 2.
PCA scores plots, PLS-DA score plots and PLS loading plots for predicting the Cmax of triptolide.
(A) PCA scores plots of the three groups (CR, HFD and control). (B) PLS-DA score plots of the three groups (CR, HFD and control). (C) The initial PLS loadings plot based on all the detected peaks/variables. Each point represents a metabolic feature detected in pre-dose serum using GC-MS. Red square, the selected variables of high VIP values were used to build the second PLS model for predicting the Cmax (high dose). (D) The secondary PLS loadings plot based on the selected peaks with high VIP values. (E) and (F) represent first and second PLS models at low dose, respectively. Glu, glutamic acid; Lac, lactic acid; Cre, creatinine.
Figure 3.
The plasma concentration–time curves of triptolide after oral administration of triptolide.
(A) low dose (0.6 mg/kg), (B), high dose (1.8 mg/kg). •, CR diet; ▪, normal diet; ▴, high fat diets. (n = 4, Mean±SD).
Table 1.
Measured Cmax and AUC of triptolide in rats plasma.
Figure 4.
Linear correlation for the prediction of PK parameters of triptolide.
(A) Cmax vs. glutamic acid at low dose; (B) Cmax vs. glutamic acid at high dose; (C) AUC0−30 min vs. glutamic acid at low dose; (D) AUC0−30 min vs. glutamic acid at high dose; (E) Cmax vs. creatinine at low dose; (F) Cmax vs. creatinine at high dose; (G) AUC0−30 min vs. creatinine at low dose; (H) AUC0−30 min vs. creatinine at high dose; (I) measured Cmax vs. predicted Cmax values at low dose; (J) measured AUC0−30 min vs. predicted AUC0−30 min values at low dose; (K) measured Cmax vs. predicted Cmax values at high dose; (L) measured AUC0−30 min vs. predicted AUC0−30 min values at high dose; (M) Predicted Cmax values including body weight vs. Predicted values excluding body weight at low dose; (N) Predicted AUC0−30 min values including body weight vs. Predicted values excluding body weight at low dose; (O) Predicted Cmax values including body weight vs. Predicted values excluding body weight at high dose; (P) Predicted AUC0−30 min values including body weight vs. Predicted values excluding body weight at high dose.
Figure 5.
Correlation between the measured and predicted values of PK parameters including both high and low doses of triptolide.
(A) measured Cmax vs. predicted Cmax values; (B) measured AUC0−30 min vs. predicted AUC0−30 min values.
Table 2.
The body weight of rats fed with different diets for two weeks.