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1.
The formation of the complex between captopril and palladium(II) chloride in Britton-Robinson buffer solution was studied. It has been established that captopril reacts with palladium(II) chloride in the pH range 2.14–9.10 to form a yellow water — soluble 2:1 complex with maximum absorbance at 380 nm. By applying different spectrophotometric methods, the conditional stability constant of the complex at the optimum pH of 4.03 and ionic strength μ = 0.5 M was found to be 108.25. The molar absorptivity was 1.875 × 103 l mol−1 cm−1. Beer's law was obeyed in concentrations up to 5 × 10−4 M captopril. The detection limit was 2.17 μg ml−1 and the relative standard deviation varied from 1.24 to 1.68%. The proposed method was found to be suitable for the accurate and reproducible analysis of captopril in water and in tablets.  相似文献   

2.
A systematic spectrophotometric study on the ion-pair formation of Bi(III)–iodide with amineptine hydrochloride, piribedil and trimebutine maleate is carried out. The optimal experimental conditions pH, concentration of Bi(III) nitrate, potassium iodide; and the nature and amount of organic solvent have been studied. The ion pairs are soluble in 1,2-dichloroethane and the optimum pH range is 2.0–2.8. By application of the methods of Sommer and Job involving non-equimolar solutions, the conditional stability constant (log K′) of the Bi(III)–piridedil ion pair (1:1) at the optimum pH of 2.4 and an ionic strength (μ) 0.1 M, was found to be 5.436. The validity of Beer's law has been tested in the concentration range 5–50 μg ml−1 in the organic layer, the relative standard deviation is less than 1%. The method is applied to the determination of these drugs in tablets without interference.  相似文献   

3.
A new method has been devised for the determination of diclofenac sodium in bulk and in pharmaceutical preparations using Eu3+ ions as the Fluorescent probe. The technique was built around the hypersensitive property of the transitions of the fluorescent probe ion, Eu3+, at 616 nm. This is normally a forbidden transition, but the interaction with diclofenac sodium, which contains a carboxylic group, makes the transition allowed and enhances the intensity of its fluorescence emission. The Eu3+ fluorescence emission at 592 nm comes from a non-hypersensitive transition and is not affected by ligation. The intensity ratio, R, defined as I592/I616, was used as a measure of the percentage of bound probe ions. Diclofenac and Eu(III) forms a (1:1) molar complex.The relative stability constant of the complex was found to be 105. A linear relationship between bound Eu3+ and the concentration of diclofenac sodium was found for concentrations from 10 to 200 μg ml−1, with a recovery percentage of 100.22 ± 2.27. The method shows a good agreement with a spectrophotometric method.  相似文献   

4.
A new stir bar sorptive extraction (SBSE) technique coupled with HPLC-UV method for quantification of diclofenac in pharmaceutical formulations has been developed and validated as a proof of concept study. Commercially available polydimethylsiloxane stir bars (Twister™) were used for method development and SBSE extraction (pH, phase ratio, stirring speed, temperature, ionic strength and time) and liquid desorption (solvents, desorption method, stirring time etc) procedures were optimised. The method was validated as per ICH guidelines and was successfully applied for the estimation of diclofenac from three liquid formulations viz. Voltarol® Optha single dose eye drops, Voltarol® Ophtha multidose eye drops and Voltarol® ampoules. The developed method was found to be linear (r = 0.9999) over 100–2000 ng/ml concentration range with acceptable accuracy and precision (tested over three QC concentrations). The SBSE extraction recovery of the diclofenac was found to be 70% and the LOD and LOQ of the validated method were found to be 16.06 and 48.68 ng/ml, respectively. Furthermore, a forced degradation study of a diclofenac formulation leading to the formation of structurally similar cyclic impurity (indolinone) was carried out. The developed extraction method showed comparable results to that of the reference method, i.e. method was capable of selectively extracting the indolinone and diclofenac from the liquid matrix. Data on inter and intra stir bar accuracy and precision further confirmed robustness of the method, supporting the multiple re-use of the stir bars.  相似文献   

5.
Capillary electrophoresis has been employed in order to determine the stability constant for the inclusion complex between β-cyclodextrin (β-CD) and nicotine. The investigation has been performed in aqueous solution at 25 and 37°C and 100 mM ionic strength in a pH interval (5.7≤pH≤9.6) relevant for systemic delivery of drugs via the oral mucosa. It has been shown that neutral nicotine binds considerably stronger than charged monoprotonated nicotine to β-CD: K1=22±12 M−1, K2=242±11 M−1 (25°C) and K1=22±12 M−1, K2=194±10 M−1 (37°C) (K1 and K2 refer to complexation by monoprotonated and neutral nicotine, respectively). Oral nicotine absorption from a sublingual tablet containing β-CD-bound nicotine is briefly discussed in connection with the use of this tablet in smoking cessation therapy.  相似文献   

6.
A simple spectrophotometric method for the determination of timonacic is presented. The procedure is based on the chelate formation with palladium(II) chloride in buffered medium. The optimum conditions for the complex formation were ascertained and the method was developed for the determination of timonacic in the concentration range of 28–48 μg ml−1. The emperical formula of the formed complex was determined, by applying different spectrophotometric methods, at optimum pH of 4.8 and an ionic strength of μ=0.5. The stoichiometric ratio was found to be 2:1 (timonacic/palladium) as calculated by the mole ratio, continuous variations and Asmus methods. The continuous variations and Nash methods were applied for the determination of the conditional stability constant of the formed yellow-water soluble complex and was found to be 3.27×107. The proposed methods was found to be suitable for the determination of timonacic in bulk and in its pharmaceutical tablets.  相似文献   

7.
Several studies highlight the presence of aluminum and diclofenac in water bodies around the world and their ability to induce oxidative stress and a negative effect on biomolecules in several aquatic species. However, studies evaluating the toxic effect of mixtures of these contaminants are scarce. The objective of this work was to determine the genotoxic, cytotoxic and embryotoxic effect of the mixture of aluminum and diclofenac at environmentally relevant concentrations on Cyprinus carpio.Juveniles of Cyprinus carpio were exposed to 0.31 μg L−1 of diclofenac, 24.45 mg L-1 of aluminum, and a mixture of both contaminants at the same concentrations for 12, 24, 48, 72 and 96 h. After the exposure time the liver, gills and blood were extracted and the following biomarkers were evaluated: micronucleus frequency, comet assay, caspase activity and TUNEL test. On the other hand, Cyprinus carpio embryos were exposed to diclofenac (0.31 μg L−1), aluminum (0.06 mg L−1) and their mixture at the same concentrations and exposure time. Microscopic observation was performed to evaluate embryonic development at 12, 24, 48, 72 and 96 h.Diclofenac (0.31 μg L−1) induces significant increases in micronucleus frequency with respect to control (p < 0.05), in all tissues. Aluminum (24.45 mg L−1) significantly increases DNA damage index in liver and blood cells with respect to control (p < 0.05). All treatments increase caspases activity in all tissues with respect to control (p < 0.05). Diclofenac increases the percentage of TUNEL-positive cells in liver and blood; while aluminum and the mixture increases it significantly in gills and blood with respect to the control (p < 0.05). The mixture significantly delays embryonic development, while aluminum and the mixture significantly increase teratogenic index with respect to control (p < 0.05). In conclusion, exposure to environmental concentrations of aluminium, diclofenac and their mixture induces genotoxic damage, cell death by apoptosis and negative effects on the development of Cyprinus carpio and the toxic response is modified by the interaction of the xenobiotics.  相似文献   

8.
The dissociation constant, Ka, of naproxen, a nonsteroidal antiinflammatory drug of the family of arylpropionic acids, has been determined in aqueous solutions at 25°C by using a potentiometric and a conductimetric techniques. The solubility limit of the drug in water, a controversial point in the literature, has been found to be less than 3×10−5 M. The interaction of naproxen with hydroxypropyl-β-cyclodextrin (HPBCD), in terms of the binding constants of the complexes formed by the CD and the nonionic (HNAP) and ionic (NAP) species of the drug, has been evaluated at 25°C as well by means of steady-state fluorescence enhancement studies. A discussion of the results, KHPBCD:HNAP=6500±400 M−1 and KHPBCD:NAP−=1400±80 M−1, emphasizing the crucial importance of the choice of the pH at a value that pH≥pKa +2 or pH≤pKa −2, is also included.  相似文献   

9.
Point and interval hypothesis tests performed to validate two simple and economical, kinetic spectrophotometric methods for the assay of lansoprazole are described. The methods are based on the formation of chelate complex of the drug with Fe(III) and Zn(II). The reaction is followed spectrophotometrically by measuring the rate of change of absorbance of coloured chelates of the drug with Fe(III) and Zn(II) at 445 and 510 nm, respectively. The stoichiometric ratio of lansoprazole to Fe(III) and Zn(II) complexes were found to be 1:1 and 2:1, respectively. The initial‐rate and fixed‐time methods are adopted for determination of drug concentrations. The calibration graphs are linear in the range 50–200 µg ml−1 (initial‐rate method), 20–180 µg ml−1 (fixed‐time method) for lansoprazole‐Fe(III) complex and 120–300 (initial‐rate method), and 90–210 µg ml−1 (fixed‐time method) for lansoprazole‐Zn(II) complex. The inter‐day and intra‐day precision data showed good accuracy and precision of the proposed procedure for analysis of lansoprazole. The point and interval hypothesis tests indicate that the proposed procedures are not biased. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

10.
The present study evaluated neurotoxic, biotransformation, genotoxic and antioxidant responses to relevant environmental concentrations of diclofenac (0.4 μg L−1) and caffeine (27.5 μg L−1), separate and combined, in adult males of the freshwater fish Astyanax altiparanae after a subchronic exposure (14 days). Fish exposed to diclofenac and caffeine, both separate and combined, revealed a neurotoxic effect through the inhibition of acetylcholinesterase activity in the muscle, while diclofenac alone and in combination caused cyclooxygenase inhibition. Caffeine alone produces genotoxicity on this species but, when combined with diclofenac, it potentiates hepatic lipoperoxidation and the inhibition of oxidative stress enzymes, while diclofenac alone or in combination produces a general inhibition of important enzymes. This study suggests that aquatic contamination produced by these pharmaceuticals has the potential to affect homeostasis and locomotion in A. altiparanae and compromise their immune system and general health.  相似文献   

11.
A direct, extraction-free spectrophotometric method was developed for the determination of benzalkonium chloride (BAC) in various eye-drops. The procedure is based on ion-pair formation between BAC and 2′,4′,5′,7′-tetrabromofluorescein (eosin-Y) which decreases the absorbance and induces a bathochromic shift of the maximum in the eosin-Y spectrum. The effects of pH, excess of reagent and ionic strength on the ion-pair formation have been studied in detail. At pH 4.40 and 9.62, the working curve is linear in the 1.98×10−6 to 2.40×10−5 M (0.7–8.5 μg cm−3) concentration range; however, the sensitivity drops to about one third in the basic solution. At pH 4.40, the analytical signal is stable for more than 60 min, while at pH 9.62 the signal changes in time and reaches the maximum value 3 min after mixing the reagent and the sample. When the active substance is β-5-isopropyl-2′deoxyuridine and the sample contains typical additives, the reproducibility of the analytical signal at pH 4.40 is R.S.D.=2.36% (n=81). In the case of such samples, the linearity of the method is somewhat dependent on the composition, but generally acceptable at the 50–150% concentration levels. Eye-drops containing tobramycin, an aminoglycoside-type antibiotic, as the active substance were analyzed at pH 9.62. This was necessary to avoid strong interference from the analyte in acidic solution. In this case the linearity of the method is limited to a narrower concentration range; however, the recovery is still acceptable at the 100% level.  相似文献   

12.
The potentiometric response characteristics of diclofenac selective electrodes based on Fe(III) tetraphenylporphyrin-chloride (Fe(III)TPP-Cl) and Fe(III) tetrakis(pentafluorophenyl)porphyrin-chloride (Fe(III)TPFPP-Cl) in different mediator solvents and ionic additives are compared. The sensitivity, working range, detection limit, response mechanism, and selectivity of the membrane sensor show a significant dependence on the type of carrier substituent and on the pH value of the sample solution. Studies performed with different amounts of cationic additive (tetra-n-octylammoniumbromide (TOABr)) and anionic additive (sodium tetraphenylborate (NaTPB)) in the membranes allowed the determination of the potentiometric mechanism of action of the used metalloporphyrins. For the analysis of real samples, Fe(III)TPFPP-Cl (type G), prepared in o-NPOE, incorporating 10 mol% of TOABr, was used. This potentiometric unit presented a linear response towards diclofenac concentrations between 10−5 and 10−2 mol l−1 ( I = 0.1 mol l−1) and slopes of about −59 mV dec−1, exhibiting a response time of 10 s in a buffered solution of ammonia–ammonium sulphate with pH 9.9. The potentiometric analysis of sodium diclofenac in pharmaceutical formulations was carried out by direct potentiometry and the obtained results were compared to those provided by HPLC, presenting relative errors inferior to 1.0%.  相似文献   

13.
Derivative spectrophotometric, colorimetric and high performance liquid chromatographic methods, for the determination of the antihistaminic cetirizine dihydrochloride in tablet form were described. Spectrophotometrically, cetirizine was determined by the measurement of its first (1D) and second (2D) derivative amplitudes at 239 (peak) and 243–233 nm (peak-to-trough), respectively. The aqueous solutions obeyed Beer's law in the concentration ranges of 1.2–10.0 and 0.8–10.0 μg ml−1 for 1D and 2D measurements, respectively. The colorimetric procedure was based on measuring the absorbency of the coloured chromogen resulted from the reaction between cetirizine sodium salt in polar solvent (DMF) and chloranil at 556 nm. The relation with concentrations was linear over 120–250 μg ml−1. Optimization of the reaction conditions was studied. At the same time, investigation of the complex formed was made with respect to its composition and the associated constant. A simple liquid chromatographic assay has been developed for the determination of cetirizine dihydrochloride in the presence of one of its synthesis precursor (hydroxyzine hydrochloride). A Bondapak-C18 column was used with a mobile phase consisting of acetonitrile/0.01 M ammonium dihydrogen phosphate (32:68, v/v) containing 0.1% w/v tetrabutyl ammonium hydrogen sulphate adjusted to pH 3 with phosphoric acid at a flow rate of 2 ml min−1. With salicylic acid as internal standard, quantitation was achieved with UV detection at 230 nm based on the peak height ratios. Beer's law was obeyed in a concentration range of 3–35 μg ml−1 and the regression line equation was derived with a correlation coefficient of 0.9999. The validity of the methods was further confirmed using the standard addition method. The proposed procedures were successfully applied to the determination of cetirizine in bulk and tablet form, with high percentage of recovery, good accuracy and precision.  相似文献   

14.
Zhang J  Li P  Guo HF  Liu L  Liu XD 《Acta pharmacologica Sinica》2012,33(11):1372-1378

Aim:

To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund''s complete adjuvant (FCA)-induced arthritic rats using prostaglandin E2 (PGE2) as a biomarker.

Methods:

The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats. PGE2 level in the rats was measured using an enzyme immunoassay. A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production. The inhibition of diclofenac on lipopolysaccharide (LPS)-induced PGE2 production in blood cells was investigated in vitro.

Results:

Similar pharmacokinetic behavior of diclofenac was found both in normal and FCA-induced arthritic rats. Diclofenac significantly decreased the plasma levels of PGE2 in both normal and arthritic rats. The inhibitory effect on PGE2 levels in the plasma was in proportion to the plasma concentration of diclofenac. No delay in the onset of inhibition was observed, suggesting that the effect compartment was located in the central compartment. An inhibitory effect sigmoid Imax model was selected to characterize the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production in vivo. The Imax model was also used to illustrate the inhibition of diclofenac on LPS-induced PGE2 production in blood cells in vitro.

Conclusion:

Arthritis induced by FCA does not alter the pharmacokinetic behaviors of diclofenac in rats, but the pharmacodynamics of diclofenac is slightly affected. A PK-PD model characterizing an inhibitory effect sigmoid Imax can be used to fit the relationship between the plasma PGE2 and diclofenac levels in both normal rats and FCA-induced arthritic rats.  相似文献   

15.
The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10−5 cm/h, licorice: 4.68·10−6 cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10−5 cm/h, licorice: 24.0·10−6 cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1142–1148, 2014  相似文献   

16.
The pH-rate profile of the pseudo-first-order rate constants for the rearrangement and hydrolysis of Ezetimibe giving (2R,3R,6S)-N,6-bis(4-fluorophenyl)-2-(4-hydroxyphenyl)-3,4,5,6-tetrahydro-2H-pyran-3-carboxamide (2) as the main product at pH of less than 12.5 and the mixture of 2 and 5-(4-fluorophenyl)-5-hydroxy-2-[(4-fluorophenylamino)-(4-hydroxyphenyl)methyl]-pentanoic acid (3) at pH of more than 12.5 in aqueous tertiary amine buffers and in sodium hydroxide solutions at ionic strength I = 0.1 mol L−1 (KCl) and at 39°C is reported. No buffer catalysis was observed and only specific base catalysis is involved. The pH-rate profile is more complex than the pH-rate profiles for the hydrolysis of simple β-lactams and it contains several breaks. Up to pH 9, the log kobs linearly increases with pH, but between pH 9 and 11 a distinct break downwards occurs and the values of log kobs slightly decrease with increasing pH of the medium. At pH of approximately 13, another break upwards occurs that corresponds to the formation of compound 3 that is slowly converted to (2R,3R,6S)-6-(4-fluorophenyl)-2-(4-hydroxyphenyl)-3,4,5,6-tetrahydro-2H-pyran-3-carboxylic acid (4). The kinetics of base-catalyzed hydrolysis of structurally similar azetidinone is also discussed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2240–2247, 2014  相似文献   

17.
A capillary gas-liquid chromatographic method suitable for the assay of the atypical neuroleptic drug zotepine in human serum or plasma was developed. A liquid-liquid extraction with three subsequent extraction steps was applied for sample preparation. The minimum detectable concentration was 1.0 ng ml−1. The within-day relative standard deviation (RSD) (n = 6) was 5.3% at 5 ng ml−1, 3.6% at 10 ng ml−1 and 6.1% at 100 ng ml−1. The day-to-day RSD (n = 6) was 9.3% at 10 ng ml−1 and 5.1% at 100 ng ml−1. Steady-state serum levels of four schizophrenic patients were measured.  相似文献   

18.
The structure of lidocaine hydrochloride (LidHCl) in propylene glycol (PG), a solvent known to enhance transdermal delivery of drugs, and the mobilities of the different kinds of ionic species appearing in this system was investigated at 25.0°C by precision conductometry. The molar conductivity was determined at several concentration between 0.4 and 10 mM and the data analysed using the conductance equation of Fuoss-Hsia and Fernandez-Prini (FHFP equation). For concentrations of up to ≈1.2 mM no higher aggregates that LidH+ were found. Using a two-parameter analysis of the equilibrium, LidH+⇔Lid+H+, we obtained the acid dissociation constant, Ka(LidH+)=2.5·10−7 (molar scale); pKa=6.60, and the limiting molar conductivity, λ0(LidH+)=0.2675 cm2/Ω per mol. For concentrations above 1.2 mM there is strong evidence of formation of ion-pairs, LidH+Cl. The ion-pair association constant was estimated to Kp≈40 indicating that about 15% of the electrolyte is in the form of LidH+Cl at the highest concentration (10 mM) investigated.  相似文献   

19.
As a pharmaceutical pollutant, doxycycline causes contamination when enters into the environment. In this research MIL-53(Fe), and its magnetic hybrid MIL-53(Fe)/Fe3O4 were synthesized and employed for removal of doxycycline from aqueous solutions. The adsorbents were characterized by XRD, SEM, BET, FTIR, EDAX, VSM and TG-DTG technique. The effect of different variables such as DOC concentration, pH, contacting time, and adsorbent dose on the removal efficiency was studied and under optimized conditions the adsorption capacity of 322 mgg−1 was obtained. The adsorption process was kinetically fast and the equilibration was attained within 30 min. The used adsorbent was easily separated from the solution by applying external magnetic field. The regenerated adsorbent retained most of its initial capacity after six regeneration steps. The effect of ionic strength was studied and it was indicated that removal of doxycycline from salt-containing water with moderate ionic strengths was quite feasible. Langmuir, Freundlich, Tempkin and Dubinin–Redushkevich isotherms were employed to describe the nature of adsorption process. The sorption data was well interpreted by the Longmuir model.  相似文献   

20.
In the present study, nitrate, chloride and sulfate anion systems were used to investigate the presence of anions on the removal of Cr(III) by Chlorella miniata. Kinetic studies suggested that the equilibrium time of Cr(III) biosorption was not affected by the presence of different sodium salts, even at the concentration of 1.0 M, and all reached equilibrium after 24 h. Equilibrium experiments showed that the effects of different anions on Cr(III) biosorption varied, and the inhibitory order was SO4 2? > Cl? > NO3 ?. Langmuir isotherm indicated that the maximum sorption capacity of C. miniata increased with the increase of pH under different anion systems. The strongest inhibition effect of the sulfate system was attributed to the formation of Cr(OH)SO4 aq. and the decrease of Cr(OH)2+ and Cr3+ in solution, while the difference of inhibitory effect in the other two anion systems could be accounted by the formation of the inner-sphere surface complex in the nitrate system and the outer-sphere surface complex in the chloride system. The present study suggested that the presence of anions greatly affected the removal of Cr(III) on C. miniata and thereby their transport in the environment.  相似文献   

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