Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensi...Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.展开更多
目的:研究中国健康志愿者单剂量静脉滴注1.0,2.0,4.0g注射用头孢替坦二钠后的药动学行为,并评价药动学参数在剂量1.0～4.0g范围内的相关性。方法:12名健康志愿者,随机三交叉试验,分别单剂量静脉滴注注射用头孢替坦二钠1.0,2.0,4.0g;测...目的:研究中国健康志愿者单剂量静脉滴注1.0,2.0,4.0g注射用头孢替坦二钠后的药动学行为,并评价药动学参数在剂量1.0～4.0g范围内的相关性。方法:12名健康志愿者,随机三交叉试验,分别单剂量静脉滴注注射用头孢替坦二钠1.0,2.0,4.0g;测定给药后24h内的血药浓度和尿药浓度,用DAS Ver 2.0软件计算药动学参数。结果:单剂量静脉滴注1.0,2.0,4.0g注射用头孢替坦二钠后,头孢替坦的消除半衰期大约为3～4h,血浆药物浓度(Cmax)随剂量增加呈线性增加(75.0±10.4～230.7±33.7μg·mL-1)。另外,曲线下面积(AUC)在1.0～4.0g剂量范围内也呈线性增加(AUC0-t:308.5±62.9～1 018.5±164.2μg.h·mL-1,AUC0-∞:314.4±63.2～1 031.7±172.5μg·h·mL-1)。24h尿药累积排泄率分别为65.6%±16.7%、44.4%±10.1%和49.1%±11.2%。结论:在剂量1.0～4.0g范围内头孢替坦呈线性药动学,Cmax、AUC的升高与剂量成正比。除2.0g剂量组t1/2性别间存在显著性差异,其他剂量组tmax、Cmax、t1/2、AUC0-t、CL、Vd、MRT0-t、尿排泄率性别间均无统计学差异。展开更多
The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma dr...The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC-MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C-0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration -time curve (ALC(0-i)) values ranged from 1.75 to 11.80 (mg ' h/L). J10688 lacked dose dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SAlD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray io...A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SAlD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. it showed good linearity over the concentration range from 3.3 to 666.7 ngfint. for the determination of Sala The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%-104% at all quality control Levels. This LC MS method was applied to the pharmacokinetic study of SaID in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 mm (C-2min) were 5756.06 +/- 719.61, 11,073.01 +/- 1783.46 and 21,077.58 +/- 5581.97 nit, for 0.25, 0.5 and I mg/kg intravenous injection, respectively. The peak plastna concentration (C-max) was 333.08 +/- 61.21 pg/L for 4 mg/kg oral administration. The area under curve (AUC(0-t)) was 14,384.379 +/- 8443.t84. 22,813.369 +/- 11,860.823, 46,406.122 +/- 27,592.645 and 8201.740+4711.961 mu g/L.h for intravenous injection (0.25, 0.5 and 1 mg/kg) and oral administration (4 mg/kg), respectively. The bioavailability of SalD) was calculated to be 4.159% +/- 0.517%. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia IMedica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
基金supported by CAMS Innovation Fund for Medical Sciences(Grant No.:2019-I2M-5e020)the National Natural Science Foundation of China(Grant No.:81503154)the National Major Scientific and Technological Special Project for Significant New Drugs Development(Grant No.:2017ZX09101002-001-005).
文摘Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.
文摘目的:研究中国健康志愿者单剂量静脉滴注1.0,2.0,4.0g注射用头孢替坦二钠后的药动学行为,并评价药动学参数在剂量1.0～4.0g范围内的相关性。方法:12名健康志愿者,随机三交叉试验,分别单剂量静脉滴注注射用头孢替坦二钠1.0,2.0,4.0g;测定给药后24h内的血药浓度和尿药浓度,用DAS Ver 2.0软件计算药动学参数。结果:单剂量静脉滴注1.0,2.0,4.0g注射用头孢替坦二钠后,头孢替坦的消除半衰期大约为3～4h,血浆药物浓度(Cmax)随剂量增加呈线性增加(75.0±10.4～230.7±33.7μg·mL-1)。另外,曲线下面积(AUC)在1.0～4.0g剂量范围内也呈线性增加(AUC0-t:308.5±62.9～1 018.5±164.2μg.h·mL-1,AUC0-∞:314.4±63.2～1 031.7±172.5μg·h·mL-1)。24h尿药累积排泄率分别为65.6%±16.7%、44.4%±10.1%和49.1%±11.2%。结论:在剂量1.0～4.0g范围内头孢替坦呈线性药动学,Cmax、AUC的升高与剂量成正比。除2.0g剂量组t1/2性别间存在显著性差异,其他剂量组tmax、Cmax、t1/2、AUC0-t、CL、Vd、MRT0-t、尿排泄率性别间均无统计学差异。
基金supported by Beijing Natural Science Foundation(7152103)the National Great Science and Technology Projects(2014ZX09507003-002 and 2012ZX09301002-2013HXW-11)the International Collaboration Project(2011DFR31240)
文摘The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC-MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C-0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration -time curve (ALC(0-i)) values ranged from 1.75 to 11.80 (mg ' h/L). J10688 lacked dose dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
基金supported by grants from The Key Project for Drug Innovation (No.2009ZX09102-123)National Natural Science Foundation of China (No.81102492)Major Scientific and Technological Special Project for "Significant New Drugs Creation" (Nos.2012ZX09301002001001 and 2013ZX09508104001002)
文摘A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SAlD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. it showed good linearity over the concentration range from 3.3 to 666.7 ngfint. for the determination of Sala The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%-104% at all quality control Levels. This LC MS method was applied to the pharmacokinetic study of SaID in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 mm (C-2min) were 5756.06 +/- 719.61, 11,073.01 +/- 1783.46 and 21,077.58 +/- 5581.97 nit, for 0.25, 0.5 and I mg/kg intravenous injection, respectively. The peak plastna concentration (C-max) was 333.08 +/- 61.21 pg/L for 4 mg/kg oral administration. The area under curve (AUC(0-t)) was 14,384.379 +/- 8443.t84. 22,813.369 +/- 11,860.823, 46,406.122 +/- 27,592.645 and 8201.740+4711.961 mu g/L.h for intravenous injection (0.25, 0.5 and 1 mg/kg) and oral administration (4 mg/kg), respectively. The bioavailability of SalD) was calculated to be 4.159% +/- 0.517%. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia IMedica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
