To investigate the pharmacokinetics of felodipine in the plasma of healthy Chinese volunteers, 30 healthy volunteers received a single oral dose of 5 mg of extended release felodipine tablets. The felodipine was extra...To investigate the pharmacokinetics of felodipine in the plasma of healthy Chinese volunteers, 30 healthy volunteers received a single oral dose of 5 mg of extended release felodipine tablets. The felodipine was extracted from the matrix with a liquid-liquid extract procedure and analyzed by high-performance liquid chromatography-tandem mass spectrometry in the multiple reaction monitoring（MRM） mode using an electrospray ion source with positive ion detection. The method was validated over a felodipine concentration range of 0. 05-10.00 ng/mL in human plasma. Its main pharmacokinetic parameters values were： ρmax = （ 1.67 ± 0. 84 ） ng/mL, occurring at （ 3.93 3± 2. 49 ） h; the plasma elimination half-life： （23. 08 3± 9. 48） h and the area under the plasma concentration versus time curve： （29. 94 ± 14. 39） ng · h/mL. The validation results demonstrated that this method showed a satisfactory precision and accuracy across the calibration range. The procedure involved minimal drug administration, sample preparation, and a 2. 5-min chromatographic run time. It was well suited to clinical studies of the drug involving large numbers of samples.展开更多
A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasm...A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography-tandem mass spectrometry. Probenecid was used as in- ternal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C18 column （50 mm × 4.6 mm i.d., 2.7μm） by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 rain. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0→143.0 for valproic acid, m/z 140.9 →140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9→239,9 for probenecid. The results showed good linearity ofvalproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges. The correlation coefficients were more than 0.998, The intra- and inter-day precision of the assay was less than 11.0% and the accuracy ranged from 2% to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring.展开更多
An analytical method based on solid phase extraction was developed and validated for analysis of adefovir in human plasma. Adefovir-d4 was used as an internal standard and Synergi MAX RP80A （150rnmx4.6mm. 41am） colu...An analytical method based on solid phase extraction was developed and validated for analysis of adefovir in human plasma. Adefovir-d4 was used as an internal standard and Synergi MAX RP80A （150rnmx4.6mm. 41am） column provided the desired chromatographic separation of compounds followed by detection with mass spectrometry. The method used simple isocratic chromato- graphic condition and mass spectrometric detection in the positive ionization mode. The calibration cuives were linear over the range of 0.50-42.47 ng/mL with the lower limit of quantitation validated at 0.50 ng/mL. Matrix effect was assessed by post-column infusion experiment to monitor phospholipids and post- extraction addition experiment was performed. The degree of matrix effect for adefovir was determined as 7.5% and ion-enhancement in five different lots of human plasma was 7.1% and had no impact on study samples analysis with 4.5 rain run time. The intra- and inter-day precision values were within 7.7% and 7.8%, respectively, for adefovir at the lower limit of quantification level. Validated bioanalytical method was successfully applied to clinical sample analysis.展开更多
A rapid and high selective ultra-performance liquid chromatography(UPLC)with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin,paeoniflorin,picroside I,picroside II,s...A rapid and high selective ultra-performance liquid chromatography(UPLC)with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin,paeoniflorin,picroside I,picroside II,saikosaponin A,and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard.One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples.Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column(100 mm×2.1 mm,1.7μm)at a flow rate of 0.4 m L/min,using gradient mode containing 0.1%formic acid in water and acetonitrile were used as the Mobile phase A and B.Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components.Calibration curves showed good linearity(R^2>0.9908)over a wide concentration range for all compounds.The intra-and interday precision(relative standard deviation)ranged 2.4%–7.0%and 2.6%–8.0%,respectively.The accuracy(relative error)was from-13.0%to 13.2%at all quality control levels.The recovery ranged from 81.1%to 92.5%.The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan-Shu Yu-Fang.The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.展开更多
A method was developed for the detection of seven microcystins(microcystin-LR, RR, YR, LA, LY, LW and LF) in surface water using automatic solid-phase extraction(A-SPE) coupled with ultra-performance liquid chromatogr...A method was developed for the detection of seven microcystins(microcystin-LR, RR, YR, LA, LY, LW and LF) in surface water using automatic solid-phase extraction(A-SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS). The automated solid-phase extraction system was used to extract microcystins(MCs) from water samples. UPLC-MS/MS was used to determine MCs concentrations in just 5 min. Method detection limits were from 0.3 to 0.9 ng/L, microcystin recoveries ranged from 83.8% to 114%, and the relative standard deviation(RSD) varied from 5.6% to 12.5%. This analytical approach was found to be simple, highly sensitive, accurate, which required little manual operation. Additionally, to validate this analytical method, A-SPE+UPLC-MS/MS was applied to characterize the concentration of MCs in Taihu Lake, Wuxi, China.展开更多
BACKGROUND In China banxia xiexin decoction(BXD)has been used in treating gastric cancer(GC)for thousands of years and BXD has a good role in reversing GC histopathology,but its chemical composition and action mechani...BACKGROUND In China banxia xiexin decoction(BXD)has been used in treating gastric cancer(GC)for thousands of years and BXD has a good role in reversing GC histopathology,but its chemical composition and action mechanism are still unknown.AIM To investigate the mechanism of action of BXD against GC based on transcriptomics,network pharmacology,in vivo and in vitro experiments.METHODS The transplanted tumor model was prepared,and the nude mouse were pathologically examined after administration,and hematoxylin-eosin staining was performed.The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry(UPLC-Q-Orbitrap MS/MS),and traditional Chinese medicines systems pharmacology platform,drug bank and the Swiss target prediction platform to predict the relevant targets,the differentially expressed genes(DEGs)of GC were screened by RNA-seq sequencing,and the overlapping targets were analyzed to obtain the key targets and pathways.Cell Counting Kit-8,apoptosis assay,cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for in vitro experiments.RESULTS All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude,with the capecitabine group and the BXD medium-dose group being the best.A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology,RNA-seq sequencing found 4767 GC DEGs,which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase(PI3K)/protein kinase B(AKt)signaling pathway.In vitro cellular experiments confirmed that BXDcontaining serum and LY294002 could inhibit the proliferation of GC cells,promote apoptosis,and inhibit the migration of GC cells by decreasing the expression of EGFR,PIK3CA,IL6,BCL2 and AKT1 in the PI3K-Akt pathway in MGC-803 expression.CONCLUSION BXD has the effect of inhibiting tumor growth rate and delaying the development of GC.Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.展开更多
L-Ergothioneine(L-EGT)possesses excellent antioxidant activity and has been used in the food,pharmaceuticals and cosmetics industries.In this study,a new efficient and sensitive ultra-performance liquid chromatography...L-Ergothioneine(L-EGT)possesses excellent antioxidant activity and has been used in the food,pharmaceuticals and cosmetics industries.In this study,a new efficient and sensitive ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was established for the quantitative determination of L-EGT in food.The sample was extracted with methanol-water(70:30,V/V),separated by hydrophilic interaction liquid chromatography(HILIC)and detected by triple-quadrupole mass spectrometry.Validation studies were carried out on different product and the limit of quantitation was 20μg/kg(milk,alcohol-free beverages,dairy products)and 40µg/kg(cereal bars,chocolate).Excellent linearity(correlation coefficient(R2)≥0.999)was achieved for L-EGT quantification in the range of 5–200 ng/mL.The recoveries of the method(83.7%−107.5%)and the relative standard deviation(RSD,0.88%−6.84%(n=6))meet the performance criteria required for the determination of L-EGT in food.Finally,the applicability of the method was tested by analysing actual samples.In general,the method developed is simple,reliable,accurate,and stable and could be useful for routine analyses of L-EGT in food.展开更多
In this study, a method based on low temperature purification （LTP） coupled with liquid chromatography-tandem mass spectrometry （LC-MS/MS） was developed for the determination of abamectin （ABA） and ivermectin （...In this study, a method based on low temperature purification （LTP） coupled with liquid chromatography-tandem mass spectrometry （LC-MS/MS） was developed for the determination of abamectin （ABA） and ivermectin （IVR） in edible oils. ABA and IVR were extracted using conventional liquid-liquid extraction followed by purification via precipitation of interfering fatty components at low temperature without an additional cleanup step. LTP is simple, easy to use, labour-saving and cost effective, and requires reduced amounts of organic solvent. The linear ranges of ABA and IVR were 5- 1000 t^g/L using matrix-matched standards. Limits of detection （LOD） and limits of quantification （LOQ） were in the range of 0.1-0.4 i^g/kg and 0.3-1.3 p^g/kg, respectively. The LOQs were below the strictest maximum residue limits established by Codex Alimentarius Commission. Recoveries at three spiked levels of 10, 20 and 100 i^g/kg in peanut oil, corn oil, olive oil, soybean oil and lard ranged from 71.1% to 119.3% with relative standard deviations of 3.2%-10.3%, which were in agreement with those obtained by the solid phase extraction method. The proposed method was utilized in the analysis of 10 edible oil samples from local market and neither ABA nor IVR was detected. As far as we know, this is the first time that LTP is applied to the determination of avermectins in edible oils.展开更多
基金Supported by the National Natural Science Foundation of China(No. 30472053)
文摘To investigate the pharmacokinetics of felodipine in the plasma of healthy Chinese volunteers, 30 healthy volunteers received a single oral dose of 5 mg of extended release felodipine tablets. The felodipine was extracted from the matrix with a liquid-liquid extract procedure and analyzed by high-performance liquid chromatography-tandem mass spectrometry in the multiple reaction monitoring（MRM） mode using an electrospray ion source with positive ion detection. The method was validated over a felodipine concentration range of 0. 05-10.00 ng/mL in human plasma. Its main pharmacokinetic parameters values were： ρmax = （ 1.67 ± 0. 84 ） ng/mL, occurring at （ 3.93 3± 2. 49 ） h; the plasma elimination half-life： （23. 08 3± 9. 48） h and the area under the plasma concentration versus time curve： （29. 94 ± 14. 39） ng · h/mL. The validation results demonstrated that this method showed a satisfactory precision and accuracy across the calibration range. The procedure involved minimal drug administration, sample preparation, and a 2. 5-min chromatographic run time. It was well suited to clinical studies of the drug involving large numbers of samples.
文摘A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography-tandem mass spectrometry. Probenecid was used as in- ternal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C18 column （50 mm × 4.6 mm i.d., 2.7μm） by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 rain. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0→143.0 for valproic acid, m/z 140.9 →140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9→239,9 for probenecid. The results showed good linearity ofvalproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges. The correlation coefficients were more than 0.998, The intra- and inter-day precision of the assay was less than 11.0% and the accuracy ranged from 2% to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring.
基金support and facilities received from Ranbaxy Research Laboratories Gurgaon,India
文摘An analytical method based on solid phase extraction was developed and validated for analysis of adefovir in human plasma. Adefovir-d4 was used as an internal standard and Synergi MAX RP80A （150rnmx4.6mm. 41am） column provided the desired chromatographic separation of compounds followed by detection with mass spectrometry. The method used simple isocratic chromato- graphic condition and mass spectrometric detection in the positive ionization mode. The calibration cuives were linear over the range of 0.50-42.47 ng/mL with the lower limit of quantitation validated at 0.50 ng/mL. Matrix effect was assessed by post-column infusion experiment to monitor phospholipids and post- extraction addition experiment was performed. The degree of matrix effect for adefovir was determined as 7.5% and ion-enhancement in five different lots of human plasma was 7.1% and had no impact on study samples analysis with 4.5 rain run time. The intra- and inter-day precision values were within 7.7% and 7.8%, respectively, for adefovir at the lower limit of quantification level. Validated bioanalytical method was successfully applied to clinical sample analysis.
基金supported financially by the National Natural Science Foundation of China (Grant No. 81973604, 81803690and 81703684)the Innovative Talents Funding of Heilongjiang University of Chinese Medicine(Grant No.2018RCD25)+8 种基金the National natural science foundation matching project (Grant No. 2018PT02)the National natural Science Foundation Matching Project (Grant No. 2017PT01)the Graduate Innovative Research Project Foundation of Heilongjiang University of Chinese Medicine (Grant No. 2019yjscx013)the Postdoctoral Initial Fund of Heilongjiang Provincethe University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (Grant No. UNPYSCT2017215 and UNPYSCT2017219)the Natural Science Foundation of Heilongjiang Province (Grant No. H2015037)the Heilongjiang University of Chinese Medicine Doctoral Innovation Foundation (Grant No. 2014bs05)the Application Technology Research and Development Projects of Harbin Technology Bureau (Grant No. 2014RFQXJ149)Heilongjiang Postdoctoral Scientific Research Developmental Fund (Grant No.LBHQ16210 and LBH-Q17161)
文摘A rapid and high selective ultra-performance liquid chromatography(UPLC)with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin,paeoniflorin,picroside I,picroside II,saikosaponin A,and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard.One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples.Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column(100 mm×2.1 mm,1.7μm)at a flow rate of 0.4 m L/min,using gradient mode containing 0.1%formic acid in water and acetonitrile were used as the Mobile phase A and B.Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components.Calibration curves showed good linearity(R^2>0.9908)over a wide concentration range for all compounds.The intra-and interday precision(relative standard deviation)ranged 2.4%–7.0%and 2.6%–8.0%,respectively.The accuracy(relative error)was from-13.0%to 13.2%at all quality control levels.The recovery ranged from 81.1%to 92.5%.The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan-Shu Yu-Fang.The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.
基金Supported by the Environmental Monitoring and Research Foundation of Jiangsu Province(1621)the Taihu Lake Pollution Prevention and Control Project of Jiangsu Province(TH2016301)Postgraduate Research and Practice Innovation Program of Jiangsu Province in 2016(KYLX16_0813)
文摘A method was developed for the detection of seven microcystins(microcystin-LR, RR, YR, LA, LY, LW and LF) in surface water using automatic solid-phase extraction(A-SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS). The automated solid-phase extraction system was used to extract microcystins(MCs) from water samples. UPLC-MS/MS was used to determine MCs concentrations in just 5 min. Method detection limits were from 0.3 to 0.9 ng/L, microcystin recoveries ranged from 83.8% to 114%, and the relative standard deviation(RSD) varied from 5.6% to 12.5%. This analytical approach was found to be simple, highly sensitive, accurate, which required little manual operation. Additionally, to validate this analytical method, A-SPE+UPLC-MS/MS was applied to characterize the concentration of MCs in Taihu Lake, Wuxi, China.
基金Supported by the Key Program of Shandong Province,China,No.2016CYJS08A01-6.
文摘BACKGROUND In China banxia xiexin decoction(BXD)has been used in treating gastric cancer(GC)for thousands of years and BXD has a good role in reversing GC histopathology,but its chemical composition and action mechanism are still unknown.AIM To investigate the mechanism of action of BXD against GC based on transcriptomics,network pharmacology,in vivo and in vitro experiments.METHODS The transplanted tumor model was prepared,and the nude mouse were pathologically examined after administration,and hematoxylin-eosin staining was performed.The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry(UPLC-Q-Orbitrap MS/MS),and traditional Chinese medicines systems pharmacology platform,drug bank and the Swiss target prediction platform to predict the relevant targets,the differentially expressed genes(DEGs)of GC were screened by RNA-seq sequencing,and the overlapping targets were analyzed to obtain the key targets and pathways.Cell Counting Kit-8,apoptosis assay,cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for in vitro experiments.RESULTS All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude,with the capecitabine group and the BXD medium-dose group being the best.A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology,RNA-seq sequencing found 4767 GC DEGs,which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase(PI3K)/protein kinase B(AKt)signaling pathway.In vitro cellular experiments confirmed that BXDcontaining serum and LY294002 could inhibit the proliferation of GC cells,promote apoptosis,and inhibit the migration of GC cells by decreasing the expression of EGFR,PIK3CA,IL6,BCL2 and AKT1 in the PI3K-Akt pathway in MGC-803 expression.CONCLUSION BXD has the effect of inhibiting tumor growth rate and delaying the development of GC.Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.
基金This work was supported by National Key Research and Development Program of China(2019YFC1606400).
文摘L-Ergothioneine(L-EGT)possesses excellent antioxidant activity and has been used in the food,pharmaceuticals and cosmetics industries.In this study,a new efficient and sensitive ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was established for the quantitative determination of L-EGT in food.The sample was extracted with methanol-water(70:30,V/V),separated by hydrophilic interaction liquid chromatography(HILIC)and detected by triple-quadrupole mass spectrometry.Validation studies were carried out on different product and the limit of quantitation was 20μg/kg(milk,alcohol-free beverages,dairy products)and 40µg/kg(cereal bars,chocolate).Excellent linearity(correlation coefficient(R2)≥0.999)was achieved for L-EGT quantification in the range of 5–200 ng/mL.The recoveries of the method(83.7%−107.5%)and the relative standard deviation(RSD,0.88%−6.84%(n=6))meet the performance criteria required for the determination of L-EGT in food.Finally,the applicability of the method was tested by analysing actual samples.In general,the method developed is simple,reliable,accurate,and stable and could be useful for routine analyses of L-EGT in food.
基金supported by National Natural Science Foundation of China(No.21305019)Special Fund forAgro-Scientific Research in the Public Interest(No.201303088)President Fund of Guangdong Academy of Agricultural Sciences(No.201218)
文摘In this study, a method based on low temperature purification （LTP） coupled with liquid chromatography-tandem mass spectrometry （LC-MS/MS） was developed for the determination of abamectin （ABA） and ivermectin （IVR） in edible oils. ABA and IVR were extracted using conventional liquid-liquid extraction followed by purification via precipitation of interfering fatty components at low temperature without an additional cleanup step. LTP is simple, easy to use, labour-saving and cost effective, and requires reduced amounts of organic solvent. The linear ranges of ABA and IVR were 5- 1000 t^g/L using matrix-matched standards. Limits of detection （LOD） and limits of quantification （LOQ） were in the range of 0.1-0.4 i^g/kg and 0.3-1.3 p^g/kg, respectively. The LOQs were below the strictest maximum residue limits established by Codex Alimentarius Commission. Recoveries at three spiked levels of 10, 20 and 100 i^g/kg in peanut oil, corn oil, olive oil, soybean oil and lard ranged from 71.1% to 119.3% with relative standard deviations of 3.2%-10.3%, which were in agreement with those obtained by the solid phase extraction method. The proposed method was utilized in the analysis of 10 edible oil samples from local market and neither ABA nor IVR was detected. As far as we know, this is the first time that LTP is applied to the determination of avermectins in edible oils.
