ABSTRACT
Gumiganghwal-tang is a traditional herbal medicine widely used for its anti-inflammatory, analgesic, and antipyretic effects. However, the safety and efficacy of its active ingredients based on an in vivo pharmacokinetic (PK) study have yet been investigated. We have established a sensitive and accurate UPLC-ESI-MS/MS method and conducted a PK study on 14 constituents of Gumiganghwal-tang through human plasma analysis. Analytical conditions were optimized according to the physicochemical properties of the 14 compounds to facilitate efficient separation and eliminate overlap or interference between peaks. KINETEX-C18 and Inertsil-C8 columns were used as UPLC stationary phases, and acetonitrile and aqueous formic acid were used as mobile phases. All the analytes were quantified with a triple quadrupole mass spectrometer using electrospray ionization in multiple reaction monitoring mode. The chromatograms of 14 bioactive compounds showed excellent elution and sensitivity, and each peak was selectively separated and quantified without interference with each other or impurities. The established analytical method was based on international guidelines and was successfully used to perform PK studies of 14 herbal ingredients in humans after oral administration with Gumiganghwal-tang tablets. The oral absorption of most active components of Gumiganghwal-tang was relatively rapid and remained considerably long in the body to be quantified in plasma up to 48 h after administration.
ABSTRACT
The purpose of this study was to investigate the pharmacokinetic properties of ephedrine, paeoniflorin, and cinnamic acid after single or multiple doses of Socheongryong-tang (SCRT) were administered to rats, and to present an example of the pharmacokinetic changes following multiple doses of an herbal medicine. SCRT is a traditional herbal medicine that has been used clinically for a long time, and its main ingredients include ephedrine, paeoniflorin, and cinnamic acid. However, studies on the pharmacokinetic properties of SCRT are insufficient, and particularly, no pharmacokinetic information has been reported for multiple doses. In this study, SCRT was administered orally to rats once or multiple times, and plasma sampled at different times was quantitatively analyzed for ephedrine, paeoniflorin, and cinnamic acid using ultra-high-performance liquid chromatography-tandem mass spectrometry. There was a difference between the pharmacokinetic parameter values of each component (especially in paeoniflorin and cinnamic acid) obtained after single or multiple doses of SCRT. The actual observed values of each component obtained after multiple doses of SCRT were clearly different from the predicted results of multiple-dose simulations based on the pharmacokinetic profiles obtained after a single dose. The results confirmed that the plasma concentrations and, thus, exposures to paeoniflorin and cinnamic acid were significantly increased when SCRT was administered multiple times, whereas that of ephedrine was not. The results of this study are expected to provide useful pharmacokinetic data for the safety and efficacy evaluation of SCRT in the future and demonstrate the necessity of pharmacokinetic comparison studies according to single or multiple oral administrations of herbal medicines.
ABSTRACT
Banhahoobak-tang is the most prescribed herbal drug in East Asia when individuals experience sudden symptoms such as sore throat or neurological symptoms. The low toxicity and high in-vivo safety of this herbal medicine has made it more attractive to patients, and it has recently been formulated as tablets. In addition, Banhahoobak-tang tablets are registered as health insurance drugs in South Korea, and clinical prescriptions and demand are increasing. However, there are very few clinical trial data as well as very little accurate content analysis and results for Banhahoobak-tang tablets. The purpose of this study was to perform in-vitro and in-vivo studies on Banhahoobak-tang tablets, including content analysis, pharmacokinetics in humans, and plasma protein binding. For this study, a UPLC-ESI-MS/MS method with polarity switching was developed for simultaneous analysis of 18 components of Banhahoobak-tang. To separate the analytes, a C8 reverse-phase column was used as the stationary phase, 0.1 % aqueous formic acid and acetonitrile as the mobile phase, and ionization and multiple reaction monitoring for quantification. The developed method was able to isolate and quantify the 18 components with good sensitivity and selectivity and was fully validated according to international analytical standards. Stability tests were also conducted on the analytes. Finally, the method was applied to in-vitro and in-vivo studies of Banhahoobak-tang tablets, and the tablet components were 52.49 ng/g to 91.00 µg/g on average. The detected components showed rapid oral absorption in humans as well as high plasma protein binding ratio overall. These results and methods can be useful not only for effectiveness and safety evaluation but also for quality control of Banhahoobak-tang tablets.
Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/analysis , Humans , Reproducibility of Results , Republic of Korea , TabletsABSTRACT
Gumiganghwal-tang is a traditional herbal medicine widely used for its anti-inflammatory,analgesic,and antipyretic effects.However,the safety and efficacy of its active ingredients based on an in vivo pharmacokinetic (PK) study have yet been investigated.We have established a sensitive and accurate UPLC-ESI-MS/MS method and conducted a PK study on 14 constituents of Gumiganghwal-tang through human plasma analysis.Analytical conditions were optimized according to the physicochemical prop-erties of the 14 compounds to facilitate efficient separation and eliminate overlap or interference be-tween peaks.KINETEX-C18 and lnertsil-C8 columns were used as UPLC stationary phases,and acetonitrile and aqueous formic acid were used as mobile phases.All the analytes were quantified with a triple quadrupole mass spectrometer using electrospray ionization in multiple reaction monitoring mode.The chromatograms of 14 bioactive compounds showed excellent elution and sensitivity,and each peak was selectively separated and quantified without interference with each other or impurities.The established analytical method was based on international guidelines and was successfully used to perform PK studies of 14 herbal ingredients in humans after oral administration with Gumiganghwal-tang tablets.The oral absorption of most active components of Gumiganghwal-tang was relatively rapid and remained considerably long in the body to be quantified in plasma up to 48 h after administration.
ABSTRACT
Asarinin, ß-eudesmol, and wogonin have common antiangiogenic activities and have the potential for use in chemotherapy. Besides, they are multivalent substances that are combined in various herbal medicines. The purpose of this study was to develop a method for simultaneous analysis of asarinin, ß-eudesmol, and wogonin, which are representative pharmacological components of Asarum heterotropoides, Atractylodes lancea, and Scutellaria baicalensis, respectively, in rat biosamples using ultraperformance liquid chromatography-tandem mass spectrometry. The three components were separated using 5 mm aqueous ammonium acetate containing 0.1% formic acid and acetonitrile as a mobile phase, equipped with a KINETEX core-shell C18 column. The analysis was quantitated on a triple-quadrupole mass-spectrometer employing electrospray ionization, and operated in the multiple reaction monitoring mode. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma, urine, and feces constituents. The developed analytical method satisfied international guidance criteria and could be successfully applied to the pharmacokinetic (PK) studies evaluating oral bioavailability of asarinin, ß-eudesmol, and wogonin after oral and intravenous administration and their urinary and fecal excretion ratios after oral administration to rats. Furthermore, the analysis was extended to PK studies following oral administration of Gumiganghwal-tang. This study was the first simultaneous analysis of the aforesaid three constituents in rat plasma, urine, and feces that also determined their PK parameters.
Subject(s)
Chromatography, High Pressure Liquid/methods , Dioxoles , Flavanones , Lignans , Plant Extracts , Sesquiterpenes, Eudesmane , Animals , Dioxoles/analysis , Dioxoles/chemistry , Dioxoles/pharmacokinetics , Flavanones/analysis , Flavanones/chemistry , Flavanones/pharmacokinetics , Lignans/analysis , Lignans/chemistry , Lignans/pharmacokinetics , Linear Models , Male , Plant Extracts/administration & dosage , Plant Extracts/pharmacokinetics , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Sesquiterpenes, Eudesmane/analysis , Sesquiterpenes, Eudesmane/chemistry , Sesquiterpenes, Eudesmane/pharmacokinetics , Tandem Mass Spectrometry/methodsABSTRACT
Exposure to particulate matter (PM) has been known to be one of the risk factors to cause allergic asthma, leading to development of respiratory disease. Banhahubak-tang tablet (BHT), a standardized Korean Medicine, is prescribed for neurasthenia, laryngopharyngitis and asthma. In this study, we investigated therapeutic effects of BHT on airway inflammation in ovalbumin (OVA) and PM smaller than 10 µm (PM10)-induced allergic asthma mice. To establish allergic asthma with airway hyper-responsiveness by PM10, BALB/c mice were sensitized and challenged with OVA and PM10, and orally administered BHT. Histological staining was performed to assess airway remodeling. Serum and bronchoalveolar lavage fluid (BALF) was collected for measuring immunoglobulin levels and counting inflammatory cells, respectively. Expression levels of Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6), pro-inflammatory cytokines and type 2 T-helper (Th2)-related cytokines were analyzed in vivo and in vitro models. Histopathological analysis demonstrated that BHT suppressed inflammatory cell infiltration, mucus hypersecretion and collagen deposition in the airway. BHT administration effectively decreased number of inflammatory cells in BALF. BHT reduced total serum Immunoglobulin E (IgE) and Immunoglobulin G (IgG) levels. In addition, BHT significantly inhibited the phosphorylation of JAK1 and STAT6 expressions. Release of pro-inflammatory cytokines and Th2-related cytokines were down-regulated by BHT. In conclusion, BHT mitigated airway inflammation by down-regulating pro-inflammatory and Th2-related cytokines via JAK1/STAT6 signaling. BHT might be a promising herbal medicine for preventing airway inflammation. Moreover, an intervention study among humans is needed to further evaluate the possible beneficial effects of BHT in allergic asthma.
Subject(s)
Anti-Asthmatic Agents/pharmacology , Asthma , Janus Kinase 1/immunology , STAT6 Transcription Factor/immunology , Signal Transduction/drug effects , Animals , Anti-Asthmatic Agents/chemistry , Asthma/drug therapy , Asthma/immunology , Asthma/pathology , Cytokines/immunology , Disease Models, Animal , Female , Lung/immunology , Lung/pathology , Mice , Mice, Inbred BALB C , Tablets , Th2 Cells/immunology , Th2 Cells/pathologyABSTRACT
The purpose of this study was to develop a method for simultaneous analysis of fourteen major active components in Gumiganghwal-tang tablet widely prescribed for cold related diseases using UPLC-ESI-MS/MS. Twelve of these 14 components were separated using 0.1% formic acid and acetonitrile as a mobile phase by gradient elution at a flow rate of 0.3â¯mL/min equipped with a KINETEX C18 column (2.1â¯×â¯50â¯mm, 1.7⯵m). The remaining two components were separated using 10â¯mM aqueous ammonium formate containing 0.01% formic acid and acetonitrile as a mobile phase by gradient elution at a flow rate of 0.2â¯mL/min equipped with an Inertsil C8-3 column (2.1â¯×â¯100â¯mm, 2.0⯵m). Quantitation of this analysis was performed on a triple quadrupole mass spectrometer using electrospray ionization technique operating in multiple reaction monitoring mode. Full validation of the analysis method was carried out, including its linearity, selectivity, sensitivity, precision, accuracy, recovery, and stability. Chromatograms showed high resolution, sensitivity, and selectivity without interference by impurities. Calibration curves of all 14 components ranged from 0.5 to 1000â¯ng/mL, displaying excellent linearity (correlation coefficients >0.99). The relative standard deviations (RSD) of intra- and inter-day were <11.75%. Recoveries were within the range 95.41-103.24% (RSD value of 1.62-9.09%). These results demonstrate that the developed method is simple, rapid, reliable, specific, accurate, and sensitive for the quantification of bioactive components of Gumiganghwal-tang. The developed method was successfully applied to the analysis of Gumiganghwal-tang tablet. The developed UPLC-ESI-MS/MS method could be useful not only for quality control, but also for effectiveness and safety evaluation of Gumiganghwal-tang tablet.
Subject(s)
Chromatography, High Pressure Liquid/methods , Plant Extracts , Tandem Mass Spectrometry/methods , Eugenol/analysis , Flavonoids/analysis , Glycyrrhizic Acid/analysis , Iridoid Glucosides/analysis , Linear Models , Plant Extracts/analysis , Plant Extracts/chemistry , Reproducibility of Results , Sensitivity and Specificity , Spectrometry, Mass, Electrospray Ionization/methods , TabletsABSTRACT
The purpose of this study was to develop a method for simultaneous analysis of schizandrin, ephedrine, paeoniflorin, and cinnamic acid as constituents of Socheongryong-tang tablet in human plasma using UPLC-MS/MS. These four components were separated using water containing 0.01% formic acid and methanol as a mobile phase by gradient elution at a flow rate of 0.3â¯mL/min with a HALO-C18 column (2.1â¯mmâ¯×â¯100â¯mm, 2.7⯵m particle size). Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique operated in multiple reaction monitoring mode. Mass transitions were m/z 432.9â¯ââ¯384.1 for schizandrin, 165.8â¯ââ¯148.1 for ephedrine, 525.0â¯ââ¯449.2 for paeoniflorin, 146.8â¯ââ¯102.9 for cinnamic acid, and 340.0â¯ââ¯324.0 for papaverine as internal standard. Liquid-liquid extraction and protein precipitation with ethyl acetate-methanol (1:2, v/v) were used to obtain these four components. Chromatograms showed high resolution, sensitivity, and selectivity without interference by plasma constituents. Calibration curves of schizandrin, ephedrine, paeoniflorin, and cinnamic acid in human plasma ranged from 0.02 to 8â¯ng/mL, 0.5 to 200â¯ng/mL, 0.2 to 80â¯ng/mL, and 1 to 400â¯ng/mL, respectively. Calibration curves of each analyte displayed excellent linearity, with correlation coefficientsâ¯>â¯0.99. For all four components, both intra- and inter-day precisions (CV%) were <5.99%. The accuracy was 99.35-103.30% for schizandrin, 98.48-104.38% for ephedrine, 97.06-103.34% for paeoniflorin, and 99.97-104.36% for cinnamic acid. This analytical method developed in this study satisfied the criteria of international guidance. It could be successfully applied to pharmacokinetic studies of schizandrin, ephedrine, paeoniflorin, and cinnamic acid after oral administration of Socheongryong-tang tablet to humans.
Subject(s)
Cinnamates/blood , Cyclooctanes/blood , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Ephedrine/blood , Glucosides/blood , Lignans/blood , Monoterpenes/blood , Polycyclic Compounds/blood , Administration, Oral , Adult , Chromatography, High Pressure Liquid/methods , Cinnamates/chemistry , Cinnamates/pharmacokinetics , Cyclooctanes/chemistry , Cyclooctanes/pharmacokinetics , Drugs, Chinese Herbal/administration & dosage , Ephedrine/chemistry , Ephedrine/pharmacokinetics , Glucosides/chemistry , Glucosides/pharmacokinetics , Humans , Lignans/chemistry , Lignans/pharmacokinetics , Linear Models , Male , Middle Aged , Monoterpenes/chemistry , Monoterpenes/pharmacokinetics , Polycyclic Compounds/chemistry , Polycyclic Compounds/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Tandem Mass Spectrometry/methods , Young AdultABSTRACT
Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN), possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D), decursinol angelate (DA), nodakenin, and decursinol (DOH), a major metabolite of D and DA. The aim of this study was to develop a simultaneous determination method for these four coumarins in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation was performed on dual columns (Kinetex® C18 column and Capcell core C18 column) with mobile phase consisting of water and acetonitrile at a flow rate of 0.3 mL/min using gradient elution. Multiple reaction monitoring was operated in positive ion mode with precursors to product ion transition values of m/z 328.9â228.8, 328.9â228.9, 409.4â248.8, and 246.8â212.9 to measure D, DA, nodakenin, and DOH, respectively. Linear calibration curves were fitted over concentration range of 0.05â»50 ng/mL for these four components, with correlation coefficient greater than 0.995. Inter- and intra-day accuracies were between 90.60% and 108.24%. These precisions were within 11.19% for all components. The established method was then applied to a pharmacokinetic study for the four coumarins after usual dosing in Korean subjects.
Subject(s)
Angelica/chemistry , Benzopyrans/blood , Butyrates/blood , Coumarins/blood , Glucosides/blood , Plant Extracts/administration & dosage , Adult , Benzopyrans/chemistry , Butyrates/chemistry , Chromatography, High Pressure Liquid , Coumarins/chemistry , Glucosides/chemistry , Humans , Male , Molecular Structure , Plant Extracts/blood , Plant Extracts/chemistry , Plant Extracts/pharmacokinetics , Tandem Mass Spectrometry , Young AdultABSTRACT
The efficiency of gypsum, as a dissolved organic carbon (DOC) coagulator, for the simultaneous immobilization of two heavy metals (Cd and Pb) and one metalloid (As) in agricultural soils near an abandoned mining site was examined. The agricultural soil was defined as long-term contaminated as As (1540mgkg-1), Cd (55mgkg-1) and Pb (1283mgkg-1) concentrations exceeded the Korean guideline values for As (25mgkg-1), Cd (4mgkg-1), and Pb (200mgkg-1). Gypsum was incorporated into the contaminated soil at 3% (w/w). In comparison two commonly using immobilizing agents (lime and compost), together with a mixture (lime+gypsum) were also included in the pot trial for the cultivation of two medical plants (A. gigas and A. macrocephala) and to evaluate the effectiveness of gypsum on As, Cd and Pb immobilization. The results showed that even though pH change-induced immobilizing agents such as lime were more effective than gypsum at immobilizing Cd and Pb, addition of gypsum also effectively reduced heavy metal phytoavailability as indicated by decreases in the concentration of Cd and Pb in medicinal plants. Furthermore, gypsum and gypsum+ lime were also most effective in reducing As concentrations in both plants studied. This was mainly attributed to significant decreases in soil DOC (48-64%) when gypsum and gypsum+lime were applied to the soil. Consequently, it was concluded that enhanced DOC coagulation with gypsum, could be considered as a promising technique for the immobilization of both metals (Cd and Pb) and metalloids (As) in agricultural soils.
Subject(s)
Agriculture , Arsenic/metabolism , Cadmium/metabolism , Calcium Sulfate/pharmacology , Lead/metabolism , Plants, Medicinal/metabolism , Soil Pollutants/metabolism , Angelica/growth & development , Angelica/metabolism , Atractylodes/growth & development , Atractylodes/metabolism , Calcium Compounds/pharmacology , Carbon/chemistry , Environmental Pollution , Metals, Heavy/metabolism , Oxides/pharmacology , Plants, Medicinal/growth & development , Soil/chemistryABSTRACT
The aim of this study was to develop an analytical method to simultaneously analyze schizandrin, schizandrol B, and gomisin N lignans in human plasma using ultra high performance liquid chromatography with tandem mass spectrometry. The three lignans were separated using a mobile phase of water and acetonitrile containing 0.02% acetic acid equipped with a Kinetex C18 column (2.1 mm × 50 mm, 1.7 µm). This analysis was achieved by multiple reaction monitoring mode in an electrospray interface. The mass transitions were m/z 433.1â384.0 for schizandrin, 398.8â367.8 for schizandrol B, and 400.6â299.8 for gomisin N. Liquid-liquid extraction with methyl tert-butyl ether was used to obtain the three lignans. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. The calibration curves for the three lignans in human plasma were 0.05-50 ng/mL and displayed excellent linearity with correlation coefficients greater than 0.99. Precision for all three lignans was within 11.23%. The accuracy was 88.3-99.0% for schizandrin, 90.6-103.4% for schizandrol B, and 90.2-103.5% for gomisin N. The developed simultaneous analytical method satisfied the criteria of international guidance and could be successfully applied to the pharmacokinetic study of three lignans after oral administration of Schisandrae Fructus extract powder to humans.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/pharmacokinetics , Lignans/blood , Tandem Mass Spectrometry , Cyclooctanes/blood , Dioxoles/blood , Humans , Polycyclic Compounds/blood , Reproducibility of ResultsABSTRACT
Development of an efficient bioinoculum is considered as an appropriate remedial approach to treat the PAHs-metal mixed contaminated sites. Therefore, we aimed to isolate a degrader able to exert an outstanding PAH catabolic potential with added traits of pH-metal-resistance, N-fix or P-solubilization from a manufactured gas plant site soil. The identified strain (MTS-6) was a first low and high molecular weight (LMW and HMW) PAHs degrading Trabulsiella sp. tolerant to pH 5. MTS-6 completely degraded the model 3 [150mgL(-1) phenanthrene (Phe)], 4 [150mgL(-1) pyrene (Pyr)] and 5 [50mgL(-1) benzo[a]pyrene (BaP)] ring PAHs in 6, 25 and 90 days, respectively. Presence of co-substrate (100mgL(-1) Phe) increased the biodegradation rate constant (k) and decreased the half-life time (t1/2) of HMW PAHs (100mgL(-1) Pyr or 50mgL(-1) BaP). The strain fixed 47µgmL(-1)N and solubilized 58µgmL(-1)P during PAH metabolism and exhibited an EC50 value of 3-4mgL(-1) for Cu, Cd, Pb and Zn. Over 6mgL(-1) metal levels was lethal for the microbe. The identified bacterium (MTS-6) with exceptional multi-functional traits opens the way for its exploitation in the bioremediation of manufactured gas plant sites in a sustainable way by employing bioaugmentation strategy.
Subject(s)
Enterobacteriaceae/metabolism , Polycyclic Aromatic Hydrocarbons/metabolism , Soil Pollutants/metabolism , Biodegradation, Environmental , Enterobacteriaceae/drug effects , Extraction and Processing Industry , Fossil Fuels , Hydrogen-Ion Concentration , Kinetics , Metals, Heavy/toxicity , Nitrogen/metabolism , Phosphorus/metabolism , Soil Microbiology , Soil Pollutants/toxicityABSTRACT
Changes in the compositions (isoflavone, protein, oil, and fatty acid) and antioxidant properties were evaluated in healthy soybeans and soybeans diseased by Phomopsis longicolla and Cercospora kikuchii. The total isoflavone content (1491.3 µg/g) of healthy seeds was observed to be considerably different than that of diseased seeds (P. longicolla: 292.6, C. kikuchii: 727.2 µg/g), with malonlygenistin exhibiting the greatest decrease (726.1 â 57.1, 351.9 µg/g). Significantly, three isoflavones exhibited a slight increase, and their structures were confirmed as daidzein, glycitein, and genistein, based on their molecular ions at m/z 253.1, 283.0, and 269.1 using the negative mode of HPLC-DAD-ESI/MS. The remaining compositions showed slight variations. The effects against 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radicals in healthy seeds were stronger than the diseased soybeans, depending upon the isoflavone level. Our results may be useful in evaluating the relationship between composition and antioxidant activity as a result of changes caused by soybean fungal pathogens.
Subject(s)
Antioxidants/pharmacology , Ascomycota/isolation & purification , Glycine max/chemistry , Plant Diseases , Plant Extracts/pharmacology , Seeds/chemistry , Isoflavones/analysis , Glycine max/microbiologyABSTRACT
A rapid, selective and sensitive ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry method about the simultaneous determination of puerarin and its major active metabolite, daidzein, in human plasma was developed and validated in order to investigate the pharmacokinetics (PKs) of Gegen after the usual oral dose administration to human. Chromatography was carried out on a Kinetex C18 column (2.1mm×50mm, 1.7µm) using 0.05% acetic acid in water and 0.05% acetic acid in methanol as mobile phase with a gradient elution. Liquid-liquid extraction with ethyl acetate in acidic condition could remove the interference and minimize the matrix effect of human plasma. The lower limit of quantification in human plasma was 0.2ng/mL for both of compounds, puerarin and daidzein. The calibration curves for puerarin and daidzein in human plasma were linear over all the concentration range of 0.2-100ng/mL with correlation coefficients greater than 0.998. This assay procedure was successfully applied to the PKs of puerarin and daidzein, after the usual oral dose of Gegen extract powder (2.56g, containing 9.984mg puerarin) in human subjects.
Subject(s)
Chromatography, High Pressure Liquid/methods , Isoflavones/blood , Isoflavones/pharmacokinetics , Tandem Mass Spectrometry/methods , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/chemistry , Humans , Isoflavones/administration & dosage , Korea , Plant Roots/chemistry , Pueraria/chemistry , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
A mixture of fly ash and phospho-gypsum (50:50, wtwt(-1)) was selected to study its potential to supply Ca and Si to rice while reducing B toxicity. We expected that the high Ca content in this mixture might convert water-soluble P to less soluble forms and thereby reduce the loss of soil P to surface runoff. The mixture was applied at rates of 0, 20, 40, and 60 Mgha(-1) in two paddy soils of contrasting textures (silt loam in Yehari and loamy sand in Daegok). The mixture significantly reduced water-soluble phosphate (W-P) in the surface soils by shifting from W-P and iron bound-P (Fe-P) to calcium bound-P (Ca-P) and aluminum bound-P (Al-P) during rice cultivation in both soils. Lancaster and Mehlich 3 extractable P increased significantly with application rate due to high contents of P and Si in the mixture. Mixtures of fly ash and phospho-gypsum should reduce P loss from rice paddy soils and increase soil fertility.
Subject(s)
Calcium Sulfate/chemistry , Carbon/chemistry , Environmental Pollution/prevention & control , Oryza/growth & development , Particulate Matter/chemistry , Phosphorus/analysis , Soil Pollutants/analysis , Soil , Calcium/metabolism , Coal Ash , Fresh Water/chemistry , Oryza/metabolism , Phosphorus/chemistry , Silicon/metabolism , Soil Pollutants/chemistry , SolubilityABSTRACT
The pharmacokinetics and pharmacodynamics of the cyclosporin A (CSA) O/W-emulsion were studied after intravenous and oral administration to Sprague-Dawley rats. Two commercial products, CIPOL Inj. and Sandimmun Neoral, were used as the reference formulations. CSA concentration and lymphocyte populations in whole blood were measured by TDxFLx and Coulter STKS, respectively. The pharmacokinetic and pharmacodynamic parameters were obtained by fitting experimental data to two-compartment model and to indirect pharmacodynamic model, respectively, using WINNONLIN. The area under the concentration-time curve (AUC), terminal half-lives (T(1/2)), total clearance (CL(t)) and relative bioavailability (F) after intravenous administration of CSA O/W-emulsion were not significantly different from those of intravenous administration of CIPOL Inj. (P>0.05). In oral administration, AUC and C(max) of CSA O/W-emulsion were significantly decreased (P<0.05), while T(1/2), MRT, T(max) and F were not significantly different (P>0.05) from those of Sandimmun Neoral. However, the area between the baseline and effect curves (ABEC) and pharmacodynamic efficiency (EFF) of CSA O/W-emulsion were significantly greater than those of references regardless of routes of administration (P<0.05). The pharmacodynamic availability (F(PD)) of CSA O/W-emulsion was 1.79- and 2.13-fold higher than that of CIPOL Inj.and Sandimmun Neroal (P<0.05), respectively.