Maximum Half-life Research Articles

Phase I pharmacokinetic study of etmaben, a malonic acid derivative

Introduction. Etmaben is a malonic acid derivative that has shown cardiotropic activity and is a promising candidate for treating ischemic heart disease and chronic heart failure. It is currently undergoing Phase I clinical trials, and its pharmacokinetics have not yet been studied in humans.Aim. The aim of the study is to investigate the pharmacokinetics of Etmaben, film-coated tablets, 300 mg (SPCPU, Russia) in healthy volunteers after fasting administration of different doses following both single and multiple dosing over a 7-day period.Materials and methods. The open-label, non-randomized clinical trial involved 48 healthy volunteers divided into 6 cohorts. Volunteers in cohort 1 received a single dose of 600 mg of etmaben, cohort 2 received 900 mg, and cohort 3 received 1200 mg. Cohorts 4, 5, and 6 received daily doses of 600 mg, 900 mg, and 1200 mg, respectively. Plasma concentrations of etmaben were measured using high-performance liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using Microsoft Excel with the Boomer extension (Department of Pharmacokinetics and Drug Metabolism, Allergan, Irvine, CA 92606, USA).Results and discussion. Pharmacokinetic parameters were calculated for 6 cohorts of 8 volunteers after single and multiple dosing of Etmaben at doses of 600, 900, and 1200 mg. The maximum plasma concentration (Cmax) of etmaben was reached on average within 0.5 h. Cmax values ranged from 2.708 ± 1.461 µg/mL to 19.871 ± 4.415 µg/mL. The maximum half-life was 0.874 ± 0.236 h, with an elimination rate constant not exceeding 1.053 ± 0.149 h–1. The mean residence time (MRT) of etmaben in plasma did not exceed 1.527 ± 0.272 h. The average volume of distribution was above 45 L, and clearance exceeded 42 L, indicating significant tissue distribution and rapid drug elimination. Due to low area under the curve values and high elimination rates, the accumulation of etmaben is minimal.Conclusion. Pharmacokinetic parameters were calculated, and averaged pharmacokinetic profiles were constructed in linear and semilogarithmic coordinates after single and multiple dosing of various etmaben doses. This study represents the first investigation of etmaben pharmacokinetics in humans, paving the way for subsequent clinical trials.

Persistence and degradation of tembotrione in loamy soil: Effect of various organic amendments, moisture regimes and temperatures

In the present study, persistence and degradation of tembotrione, a triketone herbicide, was studied in loamy soil collected from maize field. Effects of organic amendments, moistures and temperatures on tembotrione dissipation were evaluated. Soil samples were processed according to the modified QuEChERS involving dichloromethane solvent and MgSO4 without PSA. Analysis using LC-MS/MS showed >95% recoveries of tembotrione its two metabolites TCMBA and M5 from fortified soils. Tembotrione residues dissipated with time and 85.55 to 98.53% dissipation was found on 90th day under different treatments. Tembotrione dissipation increased with temperature and moisture content of the soil. Among organic amendments, highest dissipation was observed in vermicompost amended soil. Minimum and maximum half-lives of tembotrione were recorded under 35 °C (15.7 days) and air-dry (33 days) conditions, respectively. Residues of tembotrione declined with time while that of TCMBA increased steadily up to 10-45th day in different treatments and declined thereafter. Residues of M5 were not detected in our experiments. Tembotrione persistence was negatively correlated with the organic carbon (%), moisture regimes, and temperature. A good correlation between soil microbial biomass carbon and degradation was found. A two-way ANOVA indicated significant differences between the treatments at 95% confidence level (p < 0.05).

A thermostable and inhibitor resistant β-glucosidase from Rasamsonia emersonii for efficient hydrolysis of lignocellulosics biomass.

The present study reports a highly thermostable β-glucosidase (GH3) from Rasamsonia emersonii that was heterologously expressed in Pichia pastoris. Extracellular β-glucosidase was purified to homogeneity using single step affinity chromatography with molecular weight of ~ 110kDa. Intriguingly, the purified enzyme displayed high tolerance to inhibitors mainly acetic acid, formic acid, ferulic acid, vanillin and 5-hydroxymethyl furfural at concentrations exceeding those present in acid steam pretreated rice straw slurry used for hydrolysis and subsequent fermentation in 2G ethanol plants. Characteristics of purified β-glucosidase revealed the optimal activity at 80°C, pH5.0 and displayed high thermostability over broad range of temperature 50-70°C with maximum half-life of ~ 60h at 50°C, pH 5.0. The putative transglycosylation activity of β-glucosidase was appreciably enhanced in the presence of methanol as an acceptor. Using the transglycosylation ability of β-glucosidase, the generated low cost mixed glucose disaccharides resulted in the increased induction of R. emersonii cellulase under submerged fermentation. Scaling up the recombinant protein production at fermenter level using temporal feeding approach resulted in maximal β-glucosidase titres of 134,660units/L. Furthermore, a developed custom made enzyme cocktail consisting of cellulase from R. emersonii mutant M36 supplemented with recombinant β-glucosidase resulted in significantly enhanced hydrolysis of pretreated rice straw slurry from IOCL industries (India). Our results suggest multi-faceted β-glucosidase from R. emersonii can overcome obstacles mainly high cost associated enzyme production, inhibitors that impair the sugar yields and thermal inactivation of enzyme.

α and 2α decay of nuclei in the region 94≤Z≤101 using the modified generalized liquid drop model

The \ensuremath{\alpha} decay and $2\ensuremath{\alpha}$ decay of various isotopes of Pu, Am, Cm, Bk, Cf, Es, Fm, and Md in the mass region $A=218$ to 273 are investigated using the modified generalized liquid drop model (MGLDM) and universal decay law. The comparison of experimental alpha decay half-lives with the predicted half-lives proves the consistency of our calculations. As a result we broadened our investigation to also include a study of double alpha decay of these isotopes. There is a considerable interest in performing research on double alpha decay, as seen by the proposal submitted at CERN to investigate the double alpha radioactivity of $^{224}\mathrm{Ra}$. In view of this, the decay half-lives of most probable $2\ensuremath{\alpha}$ emitters, calculated using MGLDM by employing different preformation factors, are presented which can be beneficial for upcoming experimental investigations on this topic. A peak or dip in \ensuremath{\alpha} and $2\ensuremath{\alpha}$ decay half-life is witnessed which indicates the stability of parent or daughter isotopes correspondingly. Minimum and maximum half-lives for decay are observed when the daughter and parent nuclei, respectively, contain a magic number of neutrons. From our study, 126 and 162 are found as magic/semimagic numbers. A linear plot is obtained while plotting ${\mathrm{log}}_{10}{T}_{1/2}$ of all the isotopes against $Z{Q}^{\ensuremath{-}1/2}$, which emphasizes that our estimations are reliable.

Structure and decay chain of fermium isotopes using relativistic mean-field approach

In this paper, we have analyzed the ground state structural properties of fermium-isotopes in the mass range [Formula: see text] within the relativistic mean-field with NL3[Formula: see text] and Relativistic Hartree–Bogoliubov approach with DD-ME2 parameter sets. The bulk properties, such as binding energy, root mean-square charge radius, quadruple deformation parameter, chemical potentials, two-neutron separation energy and differential two- neutron separation energy, are estimated for the above Fm- isotopic chain. All the calculated observables are compared with finite range droplet model (FRDM) predictions and experimental data wherever available. The analysis predicts the existence of shell closure in the neutron-rich region of the isotopic chain at [Formula: see text]. The decay properties such as the [Formula: see text]-decay energy and corresponding half-life for three decay chains i.e. [Formula: see text]Fm, [Formula: see text]Fm and [Formula: see text]Fm are studied. Six different empirical formulae, namely; Viola-Seaborg, Royer, modified B. Alex Brown, Parkhomenko–Sobiczewski, Universal decay law and modified universal decay law are employed to ascertain the numerical dependency of the half-life for each decay energy. A comparative study of [Formula: see text]-values and half-lives for these decay chains gives a good signature of the calculated results. The half-life calculations of three decay chains suggest that [Formula: see text]Pu, [Formula: see text]Pu, [Formula: see text]Pu are shell closure nuclei having maximum half-lives, whereas [Formula: see text]Fm, [Formula: see text]Fm and [Formula: see text]Fm are shell stabilized with lower half-lives.

Pharmacokinetics of a 503B outsourcing facility-produced theophylline in dogs.

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 μg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 μg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.

Structural and decay properties of Z = 124 isotopes using RMF densities

We investigate various ground state characteristics of Z = 124 super-heavy nuclei in the region 296 ⩽ A ⩽322 using the relativistic mean field (RMF) formalism with NL3∗ parametrization. First, the calculation was carried out for the binding energy per nucleon, root-mean-square charge (rms) radii, quadrupole deformation parameter, two-neutron separation energies and other observables.The outcomes are comparable to the macro–microscopic predictions made by the Finite Range Droplet Model (FRDM) and the Weizsȧcker-Skyrme (WS) mass model. The binding energies of the parent and daughter nuclei are used to estimate the α-decay energies. Then, the Viola-Seaborg (VSS) formula and the universal decay law (UDL) have been used to explore the α-decay half-lives of two isotopes 124304,305, and the comparison is made with FRDM and WS predictions. The maximum half-lives of 124292,297 isotopes indicate the signature of shell closure.

Study into biodegradation of cocamidopropyl betaine, an amphoteric surfactant, by Pseudomonas bacteria and activated sludge

Abstract: The paper examines the biodegradation rate of cocamidopropyl betaine by bacteria of the genus Pseudomonas and activated sludge. The following microorganisms were taken as destructor strains: Pseudomonas fluorescens TR (VKPM B-4881), Pseudomonas putida TP-19 (B-6582), Pseudomonas stutzeri T (B-4904), Pseudomonas putida TSh-18 (B-2950), Pseudomonas putida TO (B-3959), Pseudomonas mendocina 2S (B-4710), Pseudomonas oleovorans TF4-1L (B-8621) and activated sludge obtained at activated sludge reactors of a Kuzbass plant. Biooxidation of surfactant samples was carried out in 250 cm3glass flasks, placed into an incubator shaker, at a constant temperature of 30ºС for pure cultures and 18ºС for activated sludge. The destructor strain should reduce the surfactant concentration to safe values within a minimum time interval. Pseudomonas stutzeri T (B-4904) and Pseudomonas fluorescens TR (B-4881) strains provided the shortest half-life of the surfactant under study – 2.5 and 2.6 days, respectively. For Pseudomonas putida TO (B-3959), Pseudomonas putida TSh-18 (B-2950) and Pseudomonas oleovorans TF4-1L (B-8621) strains, these values amounted to 3.0, 4.5 and 4.9 days, respectively. The maximum half-life of the surfactant under study was demonstrated by Pseudomonas mendocina 2S (B-4710) and Pseudomonas putida TP-19 (B-6582) microorganisms – 5.5 and 6.0 days, respectively. The maximum biodegradation of the surfactant was observed under its exposure to the biocenosis of microorganisms. Over 14 days, the concentration of cocamidopropyl betaine decreased to 0.27% of its initial concentration. The efficiency of Pseudomonas bacteria as destructors of surfactants was demonstrated. Bacteria of this genus exhibit a shorter generation time and a higher rate of biomass growth when compared to other strains and a shorter period of adaptation to surfactants when compared to activated sludge. Capable of reducing surfactant concentrations to safe values in a minimum time interval, Pseudomonas strains can be used as an effective agent in the development of technologies for wastewater purification from amphoteric surfactants.

A New Effective Multiwalled Carbon Nanotube-Foam System for Mobility Control

SummaryNanoparticles have improved a surfactant's ability to create long-lasting foam. Recent studies have widely recommended the use of silica nanoparticles to enhance foam stability. This paper presents an experimental investigation of a new and highly effective alpha olefin sulfonate (AOS)–multiwalled carbon nanotube (MWCNT) system for mobility control during gas enhanced oil recovery (EOR) operations.The new AOS–MWCNT system was evaluated for its foam stability at 150°F using a high-pressure view cell. The MWCNT was obtained as solid particles of aspect ratio up to 100 and silica nanoparticles of median size of 118 nm. The foam system was optimized for its maximum half-life by varying the concentration of the AOS and the nanotube from 0.2 to 1% and 250 to 1,000 ppm, respectively. Compatibility testing with salts was done as well. Coreflood experiments with 1.5-in.-diameter, 6-in.-long Berea sandstone cores were run to calculate the mobility reduction factor at 150°F. Nitrogen foam was injected into the core at 80% foam quality in the tertiary recovery mode, and the pressure drop across the core was measured. The formation brine had a salinity of 5 wt% sodium chloride (NaCl), and the foaming solutions were prepared with 2 wt% NaCl.The optimal concentrations of the AOS solution and the nanotubes for maximum foam stability were determined to be 0.5% and 500 ppm, respectively. The optimized AOS–MWCNT system yielded 60% greater nitrogen foam half-life (32 minutes) than an optimized AOS–silica system at 150°F. The foam half-life of a stand-alone 0.5% AOS solution was 7 minutes. In the presence of crude oil, the foam half-life decreased for all the tested systems. Coreflood experiments at 150°F showed a significant increase in the mobility reduction factor when the new AOS–MWCNT system was used as the foamer instead of stand-alone AOS or AOS–silica system. The new foaming system was stable through the duration of the experiment, yielding foam in the effluent samples. There was no formation damage observed. Salt tolerance for the MWCNT nanofluid was higher than the silica nanofluid.Foam needs to be stable for long periods of time to ensure effective mobility control during gas injection for EOR. This paper investigates a new highly effective AOS-multiwalled carbon nanotube system that outperforms the AOS–silica foaming systems in terms of foam stability and mobility control at 150°F.

Determination of Verapamil Hydrochloride and Norverapamil Hydrochloride in Rat Plasma by Capillary Electrophoresis With End-Column Electrochemiluminescence Detection and Their Pharmacokinetics Study.

In this study, we developed a new method for simultaneous determination of verapamil hydrochloride (VerHCl) and its metabolite norverapamil hydrochloride (NorHCl) by using the capillary electrophoresis-electrochemiluminescence. Under optimized experimental conditions, the linear ranges of the VerHCl and NorHCl concentrations were 0.015-10.0 and 0.060-10.0μg/mL, respectively. The linearity relations were determined using the respective regression equations y=581.2x+19.94 and y=339.4x+29.16. The respective limits of detection (S/N=3) were 0.006 and 0.024μg/mL. The proposed method was used to study the pharmacokinetics of both agents in rat plasma. The maximum concentration (Cmax), half-life time (T1/2) and time to peak (Tmax) were 683.21±74.81ng/mL, 0.52±0.21h and 2.49±0.32h for VerHCl and 698.42±71.45ng/mL, 1.14±0.26h and 2.83±0.23h for NorHCl, respectively, following oral administration of 10mg/kg VerHCl.

The influence of base pair tautomerism on single point mutations in aqueous DNA.

The relationship between base pair hydrogen bond proton transfer and the rate of spontaneous single point mutations at ambient temperatures and pressures in aqueous DNA is investigated. By using an ensemble-based multiscale computational modelling method, statistically robust rates of proton transfer for the A:T and G:C base pairs within a solvated DNA dodecamer are calculated. Several different proton transfer pathways are observed within the same base pair. It is shown that, in G:C, the double proton transfer tautomer is preferred, while the single proton transfer process is favoured in A:T. The reported range of rate coefficients for double proton transfer is consistent with recent experimental data. Notwithstanding the approximately 1000 times more common presence of single proton transfer products from A:T, observationally there is bias towards G:C to A:T mutations in a wide range of living organisms. We infer that the double proton transfer reactions between G:C base pairs have a negligible contribution towards this bias for the following reasons: (i) the maximum half-life of the G*:C* tautomer is in the range of picoseconds, which is significantly smaller than the milliseconds it takes for DNA to unwind during replication, (ii) statistically, the majority of G*:C* tautomers revert back to their canonical forms through a barrierless process, and (iii) the thermodynamic instability of the tautomers with respect to the canonical base pairs. Through similar reasoning, we also deduce that proton transfer in the A:T base pair does not contribute to single point mutations in DNA.

Persistence and degradation of cyantraniliprole in soil under the influence of varying light sources, temperatures, moisture regimes and carbon dioxide levels

In the present work, persistence and degradation of cyantraniliprole, a leading anthranilic diamide pesticide against sucking insect pests, in inceptisol soil has been studied. Effect of various factors like light source (UV-light, sunlight and dark), temperature (5, 25 and 37 °C), moisture regime (dry, field capacity and submerged) and carbon dioxide level (415 and 625 µL L−1) on dissipation was also evaluated. Formation of IN-J9Z38, a major metabolite of cyantraniliprole, was monitored in different treatments. Samples were processed as per QuEChERS method and analysis was done by HPLC-PDA. Matrix matched calibration curve, prepared in the range 0.001–10 mg L–1, indicated very good linearity (R2 > 0.99) and sensitivity (instrument limit of detection 0.001 mg L–1). Cyantraniliprole residues dissipated with time and 47.7%–98.8% dissipation was recorded on 90th day in different treatments. Minimum half-life of cyantraniliprole, i.e. 8.7 days was recorded at elevated CO2 level (625 ± 5 µL L−1) while its maximum half-life of 86.6 days was recorded at 5 °C. Metabolite IN-J9Z38 started forming from zero-day and reached the maximum on 15th to 60th day. Microbial biomass carbon, as an index of microbial activity of soil, correlated well with the degradation of cyantraniliprole.

A model-based analysis of the reactive transport behaviour of 37 trace organic compounds during field-scale bank filtration

Though bank filtration diminishes the loads of many trace organic compounds (TOrCs) present in the source water, still there is a wide uncertainty on the influence of local environmental conditions on biodegradation processes. This research addresses the fate and transport behaviour of 37 trace organic compounds at a bank filtration site in Germany over a relatively long-time span of six years. Using two-dimensional heat and reactive transport modelling in FEFLOW, TOrCs are classified according to their occurrence in bank filtration wells with a residence time of up to 4 months. We identify 12 persistent compounds, 20 reactive compounds and 5 transformation products formed during aquifer passage. Estimates of first-order biodegradation rate constants are given for six reactive compounds. Minimum biodegradation rate constants (i.e. maximum half-lives) are approximated for eight compounds only present in the surface water. For some compounds, a simple first-order degradation model did not yield satisfactory results and the behaviour appears to be more complex. Processes like sorption, redox- and/or temperature-dependent biodegradation and temperature-dependent desorption are suspected but incorporating these into the model was beyond the scope of this paper that provides an overview for many compounds. Results highlight the ability of the sub-surface to improve the water quality during bank filtration, yet at the same time show the persistence of several compounds in the aquifer.

Preparation of astaxanthin-encapsulated complex with zein and oligochitosan and its application in food processing

In this study, a simple process was developed to encapsulate astaxanthin with zein and oligochitosan, with an encapsulation efficiency of 94.34 ± 0.64% and a loading content of 6.51 ± 0.04 mg/g. The encapsulated astaxanthin was characterized and verified by Fourier transform infrared spectroscopy and morphological observation. Encapsulation significantly improved the UV-light and storage stabilities of the astaxanthin, showing the highest stability at 4 °C with a minimum k (0.0097 week−1) and maximum half-life (71.4 weeks). Furthermore, the encapsulated astaxanthin was well dispersed in liquor, apple vinegar and rice vinegar, with a maximum solubility of 40, 73.9 and 90%, respectively, leading to a significant increase in DPPH-scavenging activity. The present study provides a simple and feasible process for encapsulation of astaxanthin to increase its UV-light and storage stabilities, suggesting great potential applications of this process in the food industry.

A study of probable alpha-ternary fission fragments of 257Fm

The probable α-accompanied cold ternary fission fragments of 257Fm are studied using six types of nuclear proximity potentials. We have studied the driving potential, probability, relative yield and half-lives of possible alpha ternary fission fragments. It is clear from present study that the alpha accompanied cold ternary fission reactions of 257Fm having minimum driving potential, maximum fission yield and small fission half lives for 48Ca + 205Pt + 4He. Hence this combination is recognized as most probable alpha ternary fission fragments of 257Fm due to the presence of doubly magic nucleus 48Ca. This study finds important in the experiments on alpha ternary fission of 257Fm.

Astaxanthin from Jerusalem artichoke: Production by fed-batch fermentation using Phaffia rhodozyma and application in cosmetics

Abstract Jerusalem artichoke extract or powder was used for astaxanthin production using Phaffia rhodozyma without acidic or enzymatic inulin hydrolysis. The culture medium containing Jerusalem artichoke as carbon source was optimized, and feeding strategies, including constant, exponential, pH-stat, and substrate feedback fed-batch fermentations, were also compared for enhancing the cell biomass and astaxanthin synthesis by P. rhodozyma. Substrate-feedback fed-batch fermentation resulted in the highest dry cell weight of 83.60 g/L, with a carotenoid concentration and yield of 982.50 mg/L and 13.30 mg/g, respectively, under optimized medium components using Jerusalem artichoke extract as carbon source in a 3-L stirred-tank bioreactor. Moreover, 482.50 mg/L of carotenoids and 253.10 mg/L of astaxanthin were obtained by continuous feeding of Jerusalem artichoke powder, which was used as carbon source. Astaxanthin essence with high DPPH-scavenging activity was obtained from the extracted astaxanthin, and the DPPH free radical scavenging rate of 40 ppm astaxanthin essence reached 76.29%. When stored at 4 °C, astaxanthin essence showed the highest stability, with a minimum k value of 0.0099 week−1 and maximum half-life (t1/2) value of 70 weeks.

Expression and characterization of an enhanced recombinant heparinase I with chitin binding domain

Heparinase I (Hep I) can efficiently depolymerize heparin and heparin sulfate to oligosaccharides or unsaturated disaccharides, which resulted in loss of physiological function such as blood coagulation. In order to realize the immobilization of Hep I on chitin carriers, we cloned Hep I with the chitin binding domain (ChBD) as a chitin-affinity tag, and the Small Ubiquitin-like MOdifier (SUMO) linker as a solvation enhancer in different fusion sequence. DNA and protein gels suggested that 4 kinds of recombinants were successfully constructed and expressed in Escherichia coli (E. coli). And the triple functional heparinases isolated from cell lysate could be efficiently purified by chitin beads. After optimizing fermentation conditions, it gave the specific enzyme activities of 1.88±0.11, 3.69±0.45, 3.44±0.38, and 2.73±0.29IU/mg total proteins for ChBD-Hep I, ChBD-SUMO-Hep I, SUMO-ChBD-Hep I, and ChBD-Hep I-SUMO, respectively, with unfractionated heparin as substrate. The optimal reaction temperature and pH were determined to be 30°C and 7.0 for all the fusion enzymes. ChBD-SUMO-Hep I exhibited the maximum half-life (48min) at 30°C and best thermo-stability under 15–50°C. All the fusion enzymes showed broad pH-stability in the range of 5.4–9.0.

Serum Level Profile and Pharmacokinetic Parameters of Single Oral Dose of Metronidazole in Type II Diabetic Patients

&#x0D; Many pathophysiological processes can affect the pharmacokinetic properties of drugs in people with diabetes. The present study was deigned to evaluate the influence of diabetes mellitus (DM) on the pharmacokinetic parameters of metronidazole administered as single oral dose. Twelve healthy volunteers and twelve diabetic patients were enrolled in the present study. On day 1, a single oral dose of metronidazole 500 mg was administered orally to all participants at 9:00 am after a 10-hour fasting. Over the following 48 hours, blood samples were taken at frequent intervals and serum metronidazole concentrations were measured by a high-performance liquid chromatography method for assessment of pharmacokinetics of metronidazole. The data indicated that maximum serum concentration (Cmax) and Kelim were significantly decreased (P&lt;0.05) in diabetic patients compared with that reported in healthy subjects (25.73% and 31.51% respectively). Meanwhile, the values of time to reach maximum peak (Tmax), AUClast, AUCtotal, and half life (T½) were significantly increased (P&lt;0.05) compared with those reported in healthy subjects (20.69%, 33.65%, 30.13%, and 20.689% respectively). In conclusion, diabetes mellitus affects some of the pharmacokinetics values of orally administered metronidazole.&#x0D; Key words: Diabetes mellitus , Metronidazole, Pharmacokinetic, Serum Level

Optimization and validation of high performance liquid chromatography-ultra violet method for quantitation of metoprolol in rabbit plasma: application to pharmacokinetic studies

Purpose: To develop a sensitive, simple and validated high performance liquid chromatography (HPLC) analytical method for the determination of metoprolol tartrate in rabbit plasma. Methods: Mobile phase of methanol and 50 mM ammonium dihydrogen phosphate solution (50:50) at pH 3.05 was used for separation of metoprolol on BDS hypersil C18 column at a wavelength of 223 nm. Flow rate and retention time were 0.6 mL/min and 7.4 min, respectively. For pharmacokinetic study, rabbits were given an oral dose of 8 mg/kg of metoprolol in solution form. Blood samples were taken from jugular vein of the rabbits after drug administration and analysed by HPLC. Results: Separation of metoprolol was not interfered with other components in plasma. The calibration curve was linear in the range of 25 - 1000 ng/mL (r 2 = 0.997). Lower limits of detection (LLOD) and quantitation (LLOQ) were 8.87 and 25 ng/mL, respectively. Relative standard deviation (RSD) of intraday and inter-day precision was < 14.27 and 7.61 %, respectively. Relative error of accuracy was between 4.85 and 14.37 %. Maximum plasma concentration (C max ), time to maximum plasma concentration (T max ) and half-life (t½) after metoprolol oral administration in rabbits were 186.29 ng/mL, 0.50 h and 2.27 h, respectively. Conclusion: A simple, accurate and precise HPLC-UV method for metoprolol determination in rabbit plasma has been successfully developed and applied to a pharmacokinetic study. Keywords: HPLC-UV, Metoprolol, Pharmacokinetics, Rabbit plasma, Liquid-liquid extraction, Validation

Metabolic and Dynamic Profiling for Risk Assessment of Fluopyram, a Typical Phenylamide Fungicide Widely Applied in Vegetable Ecosystem.

Fluopyram, a typical phenylamide fungicide, was widely applied to protect fruit vegetables from fungal pathogens-responsible yield loss. Highly linked to the ecological and dietary risks, its residual and metabolic profiles in the fruit vegetable ecosystem still remained obscure. Here, an approach using modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) extraction combined with GC-MS/MS analysis was developed to investigate fluopyram fate in the typical fruit vegetables including tomato, cucumber, pepper under the greenhouse environment. Fluopyram dissipated in accordance with the first-order rate dynamics equation with the maximum half-life of 5.7 d. Cleveage of fluopyram into 2-trifluoromethyl benzamide and subsequent formation of 3-chloro-5-(trifluoromethyl) pyridine-2-acetic acid and 3-chloro-5-(trifluoromethyl) picolinic acid was elucidated to be its ubiquitous metabolic pathway. Moreover, the incurrence of fluopyram at the pre-harvest interval (PHI) of 7–21 d was between 0.0108 and 0.1603 mg/kg, and the Hazard Quotients (HQs) were calculated to be less than 1, indicating temporary safety on consumption of the fruit vegetables incurred with fluopyram, irrespective of the uncertain toxicity of the metabolites. Taken together, our findings reveal the residual essential of fluopyram in the typical agricultural ecosystem, and would advance the further insight into ecological risk posed by this fungicide associated with its metabolites.