| 1Simultaneous determination and pharmacokinetic study of polyphyllin I, polyphyllin â…¡, polyphyllin â…¥ and polyphyllin â…¦ in beagle dog plasma after oral administration of four compounds and Rhizoma Paridis Extracts by LC-MS-MSFor the first time, a rapid and specific LC-MS-MS method was developed for the analysis of polyphyllin â… , polyphyllin â…¡, polyphyllin VI and polyphyllin â…¦ in beagle dog plasma. The analysis was carried out on an Agilent Zorbax XDB-C18reversed-phase column (100×2.1mm,1.8μm) by isocratic elution with acetonitrile and water (50:50, v/v). The flow rate was0.25mL/min. All analytes including internal standards were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for polyphyllin â… , polyphyllin â…¡, polyphyllin VI and polyphyllin â…¦ ranging from10to5000ng/mL. The intra-and inter-day precisions (RSDs) were less than6.66and9.15%. The extraction recovery ranged from95.53to104.21%with RSD less than8.69%. Stability studies showed that polyphyllin â… , polyphyllin â…¢, polyphyllin â…¥ and polyphyllin â…¦ were stable in preparation and analytical process. The results indicated that the validated method was successfully used to determine the concentration-time profiles of polyphyllin I, polyphyllin â…¡, polyphyllin VI and polyphyllin â…¦.The method was applied to study the pharmacokinetics of four compounds. Six male beagle dogs were fast for12h, and then four compounds were given orally as solutions respectively. Blood samples (0.5mL) were collected from the femoral vein of dogs in their front legs before administration and after that at0.5,1,2,3,4,6,8,10,12and24h.The blood samples were immediately centrifuged at12,000rpm for10min to separate out plasma and stored at-20℃until analysis. All the values were expressed as means standard deviation (SD). The pharmacokinetic parameters were analyzed using Kinetica4.4software (Thermo Scientific, USA).Polyphyllin â… plasma concentration reached a maximum at3.17±0.41h after administration with an average Cmax of272.30±27.66ng/mL. The area under the curve (AUC0-∞) was3025.06±439.58h ng/mL and MRT was13.95±2.15h.Polyphyllin â…¡ plasma concentration reached a maximum at3.33±0.52h after administration with an average Cmax of192.40±29.11ng/mL. The area under the curve (AUC0-∞) was1955.21±94.40h ng/mL and MRT was11.77±1.83h.Polyphyllin â…¥ plasma concentration reached a maximum at3.00±0.00h after administration with an average Cmax of148.28±16.91ng/mL. The area under the curve (AUC0.∞,) was1689.75±272.60(h ng/mL) and MRT was12.98±0.45h.Polyphyllin â…§ plasma concentration reached a maximum at3.17±0.41h after administration with an average Cmax of208.33±37.92ng/mL. The area under the curve (AUC0-∞) was2243.20±352.15(h ng/mL) and MRT was12.24±1.54h.The method was applied to study the pharmacokinetics of f Rhizoma Paridis Extracts. Polyphyllin I plasma concentration reached a maximum at3.83±0.41h after administration with an average Cmax of276.01±66.28ng/mL. The area under the curve (AUC0-∞) was2610.08±1023.73(h ng/mL) and MRT was14.36±3.77h.Polyphyllin â…¡ plasma concentration reached a maximum at3.00±0.00h after administration with an average Cmax of173.01±37.55ng/mL. The area under the curve (AUC0-∞was1657.53±312.23(h ng/mL) and MRT was12.29±3.37h.Polyphyllin â…¥ plasma concentration reached a maximum at2.83±0.75h after administration with an average Cmax of143.90±29.60ng/mL. The area under the curve (AU0-∞) was1598.51±381.91(h ng/mL) and MRT was13.29±3.63h.Polyphyllin â…¦ plasma concentration reached a maximum at3.67±0.52h after administration with an average Cmax of184.43±18.38ng/mL. The area under the curve (AUC0-∞) was2077.97±463.66(h ng/mL) and MRT was14.68±4.39h.2Simultaneous determination and pharmacokinetic study of polyphyllin H, polyphyllin Vin beagle dog plasma after oral administration of Rhizoma Paridis Extracts by LC-MS-MSFor the first time, a rapid and specific LC-MS-MS method was developed for the analysis of polyphyllin H, polyphyllin V in beagle dog plasma. The analysis was carried out on an Agilent Zorbax XDB-C18reversed-phase column (100×2.1mm,1.8μm) by isocratic elution with acetonitrile and water (50:50, v/v). The flow rate was0.25mL/min. All analytes including internal standards were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for polyphyllin H, polyphyllin V ranging from1to50ng/mL. The intra-and inter-day precisions (RSDs) were less than6.66and9.15%. The extraction recovery ranged from95.53to104.21%with RSD less than8.69%. Stability studies showed that polyphyllin H, polyphyllin V were stable in preparation and analytical process. The results indicated that the validated method was successfully used to determine the concentration-time profiles of polyphyllin H, polyphyllin V.The method was applied to study the pharmacokinetics of f Rhizoma Paridis Extracts. Polyphyllin H plasma concentration reached a maximum at3.00±0.00h after administration with an average Cmax of21.28±2.19ng/mL. The area under the curve (AUC0-∞) was196.44±53.30(h ng/mL) and MRT was10.03±3.98h.Polyphyllin V plasma concentration reached a maximum at3.00±0.00h after administration with an average Cmax of23.06±3.10ng/mL. The area under the curve (AU0-∞) was239.70±37.06(h ng/mL) and MRT was11.87±1.78h.3Development and validation of a highly sensitive LC-ESI-MS/MS method for the determination of hyperoside in beagle dog plasma:application to a pharmacokinetic study.A highly sensitive, rapid assay method has been developed and validated for the analysis of hyperoside in beagle dog plasma with liquid chromatography coupled to tandemmass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves extraction of hyperoside and ginsenoside Re (IS) from beagle dog plasma. Chromatographic separation was carried out on an Agilent Zorbax XDB-C18(100×2.1mm,18μm) column by isocratic elution with acetonitrile and water (50:50, v/v) at a flow rate of0.25mL/min with a total run time of2.0min. The MS/MS ion transitions monitored were464.4±463.4for hyperoside and947.12â†'-969.60for IS. Linear responses were obtained for hyperoside ranging from10to5000/7g/mL. The intra-and inter-day precisions (RSDs) were less than5.38and3.39%and the extraction recovery ranged from94.39to100.78%with RSD less than3.82%. Stability studies showed that hyperoside was stable in preparation and analytical process.The sensitivity and specificity of the assay were found to be sufficient for accurately characterizing the plasma pharmacokinetics of hyperoside in dogs following oral administration. Hyperoside plasma concentration reached a maximum at2.17±0.41h after administration with an average maximum concentration (Cmax)of4063.87±360.91ng/mL. The area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) was29215.12±1355.75(h ng/mL) and MRT was8.8±1.3h.4Simultaneous determination of polyphyllin â… , polyphyllin â…¡, polyphyllin â…£ and polyphyllin â…¦ from Rhyzoma Paridis dog plasma by a rapid HPLC and its application to pharmacokinetic study after oral administrationFor the first time, a rapid and specific RP-HPLC-UV method was developed for the analysis of polyphyllin â… , polyphyllin â…¡, polyphyllin â…£ and polyphyllin â…¦ in beagle dog plasma. The analysis was carried out on a Diamonsil C18(2) reversed-phase column (250×4.60mm,5μm) by isocratic elution with acetonitrile and0.1%phosphoric acid (50:50, v/v). The flow rate was1.00mL/min and the detection wavelength was set at203nm. Linear responses were obtained for hyperoside ranging from0.5to50μg/mL. The intra-and inter-day precisions (RSDs) were less than9.23and9.24%with the accuracy (%) ranging from87.65to107.25%. The extraction recovery ranged from85.07to91.82%with RSD less than5.55%. Stability studies showed that polyphyllin â… , polyphyllin â…¡, polyphyllin â…¥ and polyphyllin â…¦ were stable in preparation and analytical process. The results indicated that the validated method was successfully used to determine the concentration-time profiles of polyphyllin â… , polyphyllin â…¡, polyphyllin â…¥ and polyphyllin â…¦.A rapid and specific RP-HPLC-UV method was developed for the analysis of hyperoside in beagle dog plasma. The analysis was carried out on a Diamonsil C18(2) reversed-phase column (250×4.6mm,5mm) by isocratic elution with acetonitrile and0.1%phosphoric acid (42:58, v/v). The flow rate was1.0mL/min and the detection wavelength was set at203nm. Linear response was obtained for hyperoside ranging from2to60μg/mL. The intra-and inter-day precisions (RSDs) were less than4.80and2.61%with the accuracy (%) ranging from94.81to98.49%. The extraction recovery ranged from89.85to91.32%with RSD less than7.381%. Stability studies showed that hyperoside was stable in preparation and analytical process. The results indicated that the validated method was successfully used to determine the concentration-time profiles of hyperoside.The method was applied to study the pharmacokinetics of Chonglou Kegan Capsule containing olyphyllin â… , polyphyllin â…¡, polyphyllin â…¥, polyphyllin â…¦ and hyperoside. Polyphyllin â… plasma concentration reached a maximum at2.83±0.41h after administration with an average Cmax of49.94±4.82ng/mL The area under the curve (AUC0-∞) was545.68±14.51(h ng/mL). The MRT was15.41±2.25h.Polyphyllin â…¡ plasma concentration reached a maximum at3.67±0.52h after administration with an average Cmax of19.47±2.65ng/mL. The area under the curve (AUC0-∞) was151.38±46.57(h ng/mL).The MRT was8.10±3.47h. Polyphyllin VI plasma concentration reached a maximum at3.83v0.41h after administration with an average Cmax of5.70±1.49ng/mL. The T1/2was calculated to be10.45±2.07h. The area under the curve (AUC0-∞) was70.31±12.01(h ng/mL). The MRT was15.53±2.54h.Polyphyllin VII plasma concentration reached a maximum at3.67±1.21h after administration with an average Cmax of6.80±1.37ng/mL. The area under the curve (AU0-∞) was76.79±14.32(h ng/mL).The MRT was13.80±3.29h. Hyperoside plasma concentration reached a maximum at1.67±1.67h after administration with an average Cmax of14.06±1.53ng/mL. The T1/2was calculated to be4.23±1.79h. The area under the curve (AUC0.∞was81.67±16.38(h ng/mL). The mean values of Ke was0.19±0.06h-1and MRT was6.45±1.83... |
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