Pharmacokinetics of skin and blood of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel based on micro-dialysis technology / 中国中药杂志

To further investigate the metabolism of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel in vivo,an LCMS/MS method was established for the determination of triptolide and paeoniflorin in T. wilfordii and P. lactiflora micro-emulsion gel.The extracorporeal recovery rate of blood probe was measured by concentration difference methods( incremental method and decremental method). Meanwhile,the skin and blood micro-dialysis methods of tripterine and paeoniflorin were established,and the pharmacokinetics of T. wilfordii microemulsion gel in skin and blood was studied by micro-dialysis combined with LC-MS/MS quantitative analysis. The results showed that the established method for the determination of triptolide and paeoniflorin in T. wilfordii microemulsion gel was well linear within the required range,and the specificity,recovery rate and degree of precision of the chromatography all conformed to the research requirements of micro-dialysis samples. The stability of freeze-thawing and the residual effect all conformed to the criteria of biological sample methodology. The probe recovery rates measured by incremental method and decremental method were almost consistent with the extracorporeal recovery rate test. The recovery rates of paeoniflorin in skin and blood micro-dialysis were( 30. 60±1. 09) % and( 28. 01± 1. 75) %,respectively. And the recovery rates of skin and blood micro-dialysis were( 26. 79 ± 2. 78) % and( 25. 39±1. 86) %,respectively. The intraday recovery rate of probes was stable within 11 h. The results of pharmacokinetic study showed that the Cmaxvalues of triptolide in skin and blood were( 148. 03±41. 51) and( 76. 77±15. 27) μg·L-1,respectively. And the Tmaxvalues were( 2. 33±0. 29) and( 3. 00± 0) h,respectively. The AUC0-11 hvalues were( 2 814. 05± 1 070. 37) and( 1 580. 63±208. 27) μg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 20± 0. 33) and( 4. 54± 0. 34) h,respectively. The T1/2 values were( 4. 61±4. 11) and( 1. 07± 0. 13) h,respectively. The Cmaxvalues of paeoniflorin in skin and blood were( 991. 88 ± 152. 22) and( 407. 02±120. 06) μg·L-1,respectively. The Tmaxvalues were( 2. 00±0) h and( 2. 83±0. 29) h,respectively. The AUC0-11 hvalues were( 18 430. 27±3 289. 35) and( 6 338. 59 ± 1 659. 32) μg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 29 ± 0. 16) and( 4. 00±0. 05) h,respectively. The T1/2 values were( 2. 16±0. 43) and( 1. 78±0. 48) h,respectively. The results suggested that micro-emulsion gel played a role in forming skin reservoir through percutaneous penetration. It not only could improve drug transdermal efficiency,but also control the sustained release of drug and form a long-term effect.

Pharmacokinetic comparative study on salvianolic acid B in normal and hyperlipidemic rats based on microdialysis technique combined with liquid chromatography-mass spectrometry / 中草药

Objective: To study the pharmacokinetics of salvianolic acid B (Sal B) monomer in normal and hyperlipidemic rats. Methods: The hyperlipidemic rat model was replicated successfully by using high fat diet. The detection method for microdialysis samples was established by using LC-MS. The pharmacokinetic study on Sal B in normal and hyperlipidemic rats was carried out after ig administration with low-, medium-, and high-dose (25, 50, and 100 mg/kg) Sal B using microdialysis sampling technology. The microdialysis samples were corrected with in vivo recoveries and followed by LC-MS detection. The plasma drug concentration-time curves were established by the sampling time midpoint as timeline. The pharmacokinetic fitting parameters were obtained by using non-compartment model. Results: The LC-MS detection method was sensitive, specific, and able to meet the analytical requirements. The main pharmacokinetics parameters of normal rat after ig administration with low-, medium-, and high-dose Sal B were as follows: Cmax were (38.551 ± 6.692), (95.550 ± 12.544), and (204.251 ± 20.342) ng/mL, respectively, tmax were (1.125 ± 0.000), (1.375 ± 0.125), and (1.125 ± 0.125) h, respectively, AUC0-t were (65.995 ± 12.367), (178.806 ± 33.592), and (422.836 ± 72.344) h∙ng/mL, respectively, MRT were (2.002 ± 0.061), (1.911 ± 0.042), and (1.955 ± 0.053) h, respectively; The main pharmacokinetics parameters of hyperlipidemia rats after ig administration with low-, medium- and high-dose Sal B were as follows: Cmax were (49.265 ± 7.317), (113.986 ± 15.294), and (246.454 ± 30.476) ng/mL, tmax were (1.125 ± 0.000), (1.125 ± 0.125), and (1.375 ± 0.125) h, respectively, AUC0-t were (96.013 ± 15.384), (207.192 ± 32.676), and (486.843 ± 89.276) h∙ng/mL, respectively, MRT were (2.161 ± 0.049), (2.089 ± 0.033), and (2.097 ± 0.035) h, respectively. Conclusion: The LC-MS method is suitable for the analysis with the high sensitivity and strong specificity. The pharmacokinetics parameters of Sal B of hyperlipidemia rats, such as Cmax, AUC0-t, and MRT, are higher than those of normal rats, which is conducive to play a therapeutic role, but without statistical significance.

Establishment of skin and blood microdialysis sampling method of sinomenine and triptolide in vivo / 中草药

Objective: To establish skin and blood microdialysis (MD) method of sinomenine and triptolide. Methods: Incremental method was applied and the recovery rate of sinomenine and triptolide was used as an index to investigate the impact of perfusion fluid flow rate to the recovery (R). The flow rate and sampling interval were then determined according to the R and actual operation; The reduction method and incremental method were applied in the in vitro study to investigate impact of perfusate concentration to the R and a transfer rate (D) and the proportional relationship between them; Reduction method was applied in the in vivo study to investigate and determine the stability of the probe recoveries. Results: The recovery of skin and blood probes in vitro of sinomenine and triptolide increased with the flow rate in the range of 0.5-2.5 μL/min. The flow rate was determined to be 1 μL/min and the sampling interval was determined to be 0.5 h; The R of sinomenine and triptolide in skin and blood probes in vitro and D was stable and equal despite of change of sinomenine concentration in 10-40 μg/mL and triptolide concentration in 3-12 μg/mL, indicating that the effect of drug concentration on the MD probe R was small and that R could be replaced by the D; The D in vivo using MD method was measured at 10 h. The D values of sinomenine skin and blood probe were (41.27 ± 0.87)% and (37.8 ± 0.99)%, respectively and those of triptolide were (44.68 ± 1.28)% and (51.35 ± 1.15)%, respectively, indicating that the D of sinomenine and triptolide was stable within 10 h. Conclusion: The established method of sinomenine and triptolide in MD can be applied to investigate the kinetics in skin and blood after sc administration of formulation.

Pharmacokinetic study on Danshen Decoction with multiple dosing to awake animal by blood microdialysis method combined with LC-MS / 中草药

Objective: To carry out the pharmacokinetic study in awake animal after multiple dosing of Danshen (Salvia miltiorrhiza) Decoction by blood microdialysis method combined with LC-MS. Methods: The pharmacokinetic study was carried out with awake rabbits as experimental animal, Danshen Decoction as tool drug, and Danshensu as evaluation index combining with microdialysis sampling and LC-MS detection technology after intraday multiple dosing. The pharmacokinetic parameters were obtained by non-compartmental model method. Results: The pharmacokinetic study pattern of multiple dosing was established in awake animal, and the whole process dynamic characteristics were collected. The method was stable, reliable, and simple. Conclusion: This study can make the reference to similar study for other drugs.

Pharmacokinetic Studies of Sinomenine by Blood Microdialysis Technique / 广州中医药大学学报

[Objective] To explore the feasibility and advantages of blood microdialysis technique for the pharmacokinetic study of sinomenine. [Methods] In this study, rats served as the experimental subjects and sinomenine was administered to the rats by intravenous injection. With microdialysis technique for blood sampling, the blood concentration of sinomenine was determined by high performance liquid chromatography (HPLC) and the associated pharmacokinetic parameters were analyzed by 3p97 program. [Results] The pharmacokinetics process of sinomenine in rats presented as the two-compartment model. The half-life of distribution phase was 10.98min and that of elimination phase was 44.71 min. [Conclusion] It is feasible to study pharmacokinetic parameters of sinomenine by using blood microdialysis technique. In comparison with the traditional technique, blood microdialysis technique is superior to the examination of drug blood concentration .