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34. After administration of StA, blood samples were collected at 0.033, 0.167, 0.5, 1, 2, 4, 8, 12, 24, and 36?h, respectively. Plasma samples were obtained after centrifugation of the collected blood samples at 3,000?rpm for 5?min. Subsequently, in 100?��L plasma which was taken from the supernatant, 200?��L of 50% acetonitrile and 50% methanol were added. After vortexing for 20?s and centrifuging at 12,000?rpm for 10?min, the supernatant was collected and filtered through a 0.22?��m membrane, of which 20?��L was injected into the chromatographic Quinapyramine system for analysis. Pharmacokinetic parameters were calculated with DAS 3.0 software (Shanghai, China). 3. Results and Discussion 3.1. Method Validation The selectivity of the method was demonstrated by typical chromatograms of blank plasma, blank plasma spiked with standard solution at the concentration of 1?��g/mL, and plasma sample obtained after administration of StA. There were no significant endogenous peaks directly interfering with the detection of analytes in plasma, respectively (data not shown). The retention time of StA was about 6.1?min. Under the established analysis method, the lower limit of detection (LOD) and lower limit of quantitation (LOQ) of StA were 0.02 and 0.025?��g/mL for plasma sample. In the range of 0.25�C25?��g/mL for plasma samples, the calibration curve of StA showed good linearity (r2 �� 0.999) using a 1/x2 weighted linear regression. The intraday and interday precision and accuracy in rat plasma were evaluated by using the low, medium, and high concentration of QC samples (Table 1). The accuracy values learn more were from 101.9 �� 2.32% to 104.5 �� 4.41% in the plasma. The overall plasma extraction recovery of StA at both medium and high concentration (n = 6) surpassed 88.3 �� 4.53% (Table 1). Table 1 Accuracy, extraction recovery, and calibration curve of StA in rat plasma (n = 5). 3.2. Pharmacokinetic Study The concentration-time profiles of StA in rat plasma were presented in Figure 1. Noncompartmental model of DAS 2.0 program was used to determine the major pharmacokinetic (PK) parameters. It showed that StA's PK profile exhibited two processes of rapid distribution and slow excretion after administration (Figure 1). The t1/2 of all tested dosage forms in present study was ranged from 12 to 16?h. As shown in Table 2, when the doses GDC-0449 molecular weight of StA of different formulations were normalized, the value of AUC(0-t)/dose of StA of TPAP formulation was significantly lower than that of nanoemulsion formulation after intragastric administration. It suggests that the TPAP formulation of StA was not efficient for oral absorption. In order to increase the bioavailability of StA, we had developed nanoemulsion of StA (nanoemulsion formulation). Compared with TPAP formulation, the absolute bioavailability of StA in nanoemulsion formulation significantly increased from 4.3% to 47.3%.
