Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the m...Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.展开更多
Due to the nature of ultra-short-acting opioid remifentanil of high time-varying,complex compartment model and low-accuracy of plasma concentration prediction,the traditional estimation method of population pharmacoki...Due to the nature of ultra-short-acting opioid remifentanil of high time-varying,complex compartment model and low-accuracy of plasma concentration prediction,the traditional estimation method of population pharmacokinetics parameters,nonlinear mixed effects model(NONMEM),has the abuses of tedious work and plenty of man-made jamming factors.The Elman feedback neural network was built.The relationships between the patients’plasma concentration of remifentanil and time,patient’age,gender,lean body mass,height,body surface area,sampling time,total dose,and injection rate through network training were obtained to predict the plasma concentration of remifentanil,and after that,it was compared with the results of NONMEM algorithm.In conclusion,the average error of Elman network is 6.34%,while that of NONMEM is 18.99%.The absolute average error of Elman network is 27.07%,while that of NONMEM is 38.09%.The experimental results indicate that Elman neural network could predict the plasma concentration of remifentanil rapidly and stably,with high accuracy and low error.For the characteristics of simple principle and fast computing speed,this method is suitable to data analysis of short-acting anesthesia drug population pharmacokinetic and pharmacodynamics.展开更多
Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/m...Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/mL are associated with toxicity. The aim of the study was to appreciate EFV plasmas concentrations profile and the association between plasma levels and various characteristics in Beninese patients treated by a 600 mg standard daily-dose. Blood samples were collected and EFV plasma levels were measured by liquid chromatography coupled with mass spectrometry detection in HIV-infected patients receiving EFV in combination with other antiretroviral drugs for at least 14 days. Adverse effects occurring during treatment were collected through a questionnaire. An over-exposure to EFV among Beninese HIV patients were observed, with 46.4% of patients presenting EFV concentration above 4,000 ng/mL, although adverse effects were tolerated indicating that antiretroviral treatment is safe. The measurement of plasma concentration at the steady-state could contribute to early detection of treatment failure and adapt treatment in subjects presenting serious adverse effects within context of therapeutic drug monitoring.展开更多
8,2＇-Diprenylquercetin 3-methyl ether with significant anti-breast cancer activity is the main constituent of Tibetan medicine Sinopodophylli Fructus. In the present study, we developed and validated a rapid and sens...8,2＇-Diprenylquercetin 3-methyl ether with significant anti-breast cancer activity is the main constituent of Tibetan medicine Sinopodophylli Fructus. In the present study, we developed and validated a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the determination of 8,2＇-diprenylquercetin 3-methyl ether in rat plasma. 8-Prenylkaempferol was used as the internal standard. The separation was carried out using Waters ACQUITY UPLC BEH C18 column （2.1 mm×100 ram, 1.7 μm） with a mobile phase consisting of acetonitrile and 0.1% formic acid in water on a gradient program at a flow rate of 0.4 mL＇min-1 and temperature of 30 ℃. Triple quadrupole mass spectrometric detection in negative ion mode was used for multiple-reaction monitoring of the transitions at m/z 451.30→177.25 and m/z 353.25→298.15 for 8,2＇-diprenylquercetin 3-methyl ether and 8-prenylkaempferol, respectively. The calibration curves were linear within the concentration range 0.1-2000 ng/mL （r = 0.9954）. The recoveries were 103%-115%, and the results were consistent across low, middle and high concentration levels. The intra- and inter-day precisions were within 15%, and the bias was between --6%-15%. This method was simple, rapid and sensitive, which could be applied to the determination of 8,2＇-diprenylquercetin 3-methyl ether in plasma and pharmacokinetic study in rats. Pharmacokinetic test indicated that the peak plasma concentration occurred in 2 h after the female rats were intragastrically administered with 8,2＇-diprenylquercetin 3-methyl ether at the dose of 100 mg/kg, and the biological half-life was 6.79 h. The blood drug concentration maintained equal amount for 20 h, which was conducive to the in vivo effects of drugs.展开更多
A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol c...A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard (IS). The chromatographic separation was performed on a Zorbax SB-Cjg column (3.5 pm, 2.1 mmx 100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid (v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m/z 515.3->352.9 for isochlorogenic acid B and m/z 227.1-143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5-2500 ng/mL (r^2= 0.9982). The intra- and inter-day precisions (R.S.D.%) were less than 12.46%, and the accuracy (R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg.展开更多
OBJECTIVE:To compare the effects of carbamylβ-methylcholine chloride(CMCC) administered by intra-acupuncture point injection(IAI),intramuscular injection(IMI),and intravenous injection(IVI),and to analyze the mechani...OBJECTIVE:To compare the effects of carbamylβ-methylcholine chloride(CMCC) administered by intra-acupuncture point injection(IAI),intramuscular injection(IMI),and intravenous injection(IVI),and to analyze the mechanisms.METHODS:In the IAI group,CMCC was injected into the Zusanli acupoint(ST 36) immediately after 30-min stimulation by electro-acupuncture(EA) at the acupoints,and into the femoral vein and skeletal muscle in IVI and IMI groups,respectively.Intra-gastric pressure was detected.The plasma concentration of CMCC was measured at various times.RESULTS:The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other groups.In the IAI group,this effect was significantly stronger than that in the IMI group at 2 min and 15 min,but not significantly different between the two groups at 5 min and 30 min.Plasma concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min,but higher than that in the IMI group.The concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5,15 and 30 min,indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI group.There was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all groups.CONCLUSION:The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI,which correlated with the blood concentration of CMCC.展开更多
文摘Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.
基金Project(31200748)supported by the National Natural Science Foundation of China
文摘Due to the nature of ultra-short-acting opioid remifentanil of high time-varying,complex compartment model and low-accuracy of plasma concentration prediction,the traditional estimation method of population pharmacokinetics parameters,nonlinear mixed effects model(NONMEM),has the abuses of tedious work and plenty of man-made jamming factors.The Elman feedback neural network was built.The relationships between the patients’plasma concentration of remifentanil and time,patient’age,gender,lean body mass,height,body surface area,sampling time,total dose,and injection rate through network training were obtained to predict the plasma concentration of remifentanil,and after that,it was compared with the results of NONMEM algorithm.In conclusion,the average error of Elman network is 6.34%,while that of NONMEM is 18.99%.The absolute average error of Elman network is 27.07%,while that of NONMEM is 38.09%.The experimental results indicate that Elman neural network could predict the plasma concentration of remifentanil rapidly and stably,with high accuracy and low error.For the characteristics of simple principle and fast computing speed,this method is suitable to data analysis of short-acting anesthesia drug population pharmacokinetic and pharmacodynamics.
文摘Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/mL are associated with toxicity. The aim of the study was to appreciate EFV plasmas concentrations profile and the association between plasma levels and various characteristics in Beninese patients treated by a 600 mg standard daily-dose. Blood samples were collected and EFV plasma levels were measured by liquid chromatography coupled with mass spectrometry detection in HIV-infected patients receiving EFV in combination with other antiretroviral drugs for at least 14 days. Adverse effects occurring during treatment were collected through a questionnaire. An over-exposure to EFV among Beninese HIV patients were observed, with 46.4% of patients presenting EFV concentration above 4,000 ng/mL, although adverse effects were tolerated indicating that antiretroviral treatment is safe. The measurement of plasma concentration at the steady-state could contribute to early detection of treatment failure and adapt treatment in subjects presenting serious adverse effects within context of therapeutic drug monitoring.
基金National Natural Science Foundation of China(Grant No.81673590)National Key Technology R&D Program "New Drug Innovation" of China(Grant No.2013ZX09103002-006)
文摘8,2＇-Diprenylquercetin 3-methyl ether with significant anti-breast cancer activity is the main constituent of Tibetan medicine Sinopodophylli Fructus. In the present study, we developed and validated a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the determination of 8,2＇-diprenylquercetin 3-methyl ether in rat plasma. 8-Prenylkaempferol was used as the internal standard. The separation was carried out using Waters ACQUITY UPLC BEH C18 column （2.1 mm×100 ram, 1.7 μm） with a mobile phase consisting of acetonitrile and 0.1% formic acid in water on a gradient program at a flow rate of 0.4 mL＇min-1 and temperature of 30 ℃. Triple quadrupole mass spectrometric detection in negative ion mode was used for multiple-reaction monitoring of the transitions at m/z 451.30→177.25 and m/z 353.25→298.15 for 8,2＇-diprenylquercetin 3-methyl ether and 8-prenylkaempferol, respectively. The calibration curves were linear within the concentration range 0.1-2000 ng/mL （r = 0.9954）. The recoveries were 103%-115%, and the results were consistent across low, middle and high concentration levels. The intra- and inter-day precisions were within 15%, and the bias was between --6%-15%. This method was simple, rapid and sensitive, which could be applied to the determination of 8,2＇-diprenylquercetin 3-methyl ether in plasma and pharmacokinetic study in rats. Pharmacokinetic test indicated that the peak plasma concentration occurred in 2 h after the female rats were intragastrically administered with 8,2＇-diprenylquercetin 3-methyl ether at the dose of 100 mg/kg, and the biological half-life was 6.79 h. The blood drug concentration maintained equal amount for 20 h, which was conducive to the in vivo effects of drugs.
基金Chinese Academy of Medical Sciences(Grant No.CAMS-2017-I2M-1-011)
文摘A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard (IS). The chromatographic separation was performed on a Zorbax SB-Cjg column (3.5 pm, 2.1 mmx 100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid (v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m/z 515.3->352.9 for isochlorogenic acid B and m/z 227.1-143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5-2500 ng/mL (r^2= 0.9982). The intra- and inter-day precisions (R.S.D.%) were less than 12.46%, and the accuracy (R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg.
基金Supported by Beijing Natural Science Foundation Grant(grant number 7072053)the National Basic Research Pro-gram of China (973 Program) of China Grant(2006CB504506)+1 种基金the National Natural Science Foundationof China (NSFC) Grants (30873295 and 30801485)the Business fees of China academy of Chinese Medical Sciences for independent Topics of Basic Researchers (ZZ2007001)
文摘OBJECTIVE:To compare the effects of carbamylβ-methylcholine chloride(CMCC) administered by intra-acupuncture point injection(IAI),intramuscular injection(IMI),and intravenous injection(IVI),and to analyze the mechanisms.METHODS:In the IAI group,CMCC was injected into the Zusanli acupoint(ST 36) immediately after 30-min stimulation by electro-acupuncture(EA) at the acupoints,and into the femoral vein and skeletal muscle in IVI and IMI groups,respectively.Intra-gastric pressure was detected.The plasma concentration of CMCC was measured at various times.RESULTS:The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other groups.In the IAI group,this effect was significantly stronger than that in the IMI group at 2 min and 15 min,but not significantly different between the two groups at 5 min and 30 min.Plasma concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min,but higher than that in the IMI group.The concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5,15 and 30 min,indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI group.There was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all groups.CONCLUSION:The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI,which correlated with the blood concentration of CMCC.
