RESUMEN
A rodent model of malaria, Plasmodium berghei was used to assess the antimalarial potential of dinitroaniline herbicides. Trifluralin, pendimethalin, oryzalin, and benfluralin were all active against P. berghei in vitro at, or close to, submicromolar concentrations, with a rank order of potency similar to that against other protozoa. The dinitroanilines did not elicit a cytotoxic effect against a mammalian cell line at concentrations 100-fold higher than those for activity against P. berghei. Neither trifluralin nor oryzalin exhibited any antimalarial activity in vivo after oral administration at the maximum dose tolerated by the host. In a pharmacokinetic study, it was found that the lack of in vivo antimalarial activity was due to poor absorption. Other DNs which have better absorption characteristics than either trifluralin or oryzalin may offer more scope for antimalarial activity in vivo.
Asunto(s)
Malaria/tratamiento farmacológico , Plasmodium berghei/efectos de los fármacos , Sulfanilamidas , Trifluralina/farmacología , Trifluralina/uso terapéutico , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Células Cultivadas , Cloroquina/farmacología , Cloroquina/uso terapéutico , Dinitrobencenos/farmacología , Dinitrobencenos/uso terapéutico , Modelos Animales de Enfermedad , Eritrocitos/parasitología , Malaria/parasitología , Pruebas de Sensibilidad Parasitaria/métodos , Plasmodium berghei/crecimiento & desarrollo , Ratas , Ratas Endogámicas LewRESUMEN
The route of formation and identification of the principal degradation products of thimerosal (thiomersal) has been undertaken. The initial oxidation to dithiosalicylic acid is followed by cleavage of the disulphide bond of the dithiosalicylic acid by the ethylmercuric ion to reform 1.5 mol of thimerosal with concurrent oxidation to form 0.5 mol of 2-sulfinobenzoic acid for each mole of dithiosalicylic acid. In the presence of copper ions 2-sulfobenzoic acid was also formed. A mechanism has been proposed which accounts for the stoichiometry of the cleavage reaction observed and the significance of the reaction is discussed.
Asunto(s)
Antiinfecciosos Locales/química , Compuestos de Etilmercurio/química , Fungicidas Industriales/química , Salicilatos/química , Timerosal/química , Cobre , Estabilidad de Medicamentos , Ácido Edético , Oxidación-ReducciónRESUMEN
The kinetics of the reaction of sulfamethoxazole (SMX) in 5% w/v glucose to form the corresponding alpha- and beta-glucosylamines over the pH range of 0.80-6.88 at 37 degrees C has been investigated. The identity of the glucosylamines was determined by 1H-nuclear magnetic resonance spectroscopy of an authentic sample of the alpha-glucosylamine (USP) and the reaction products, and by interconversion of this compound to the corresponding beta-anomer. The reaction followed pseudo first-order reversible kinetics and involved specific acid and general acid-base catalysis. The pH-rate profile demonstrated that over the pH range of 0.80-2.90 and 5.50-6. 88 the reactions were dependent on H(+) concentration but pH independent between pH 3.00-5.45, which reflects the influence of ionization of SMX and the glucosylamines on the reversible reaction. Interpretation of the data with respect to kinetic models and rate equations for the formation and hydrolysis of the glucosylamines was investigated. Temperature dependence studies followed the Arrhenius equation with an Ea of 49.28 kJ mol(-1) for the forward and 63.46 kJ mol(-1) for the reverse reaction at pH 2.89 respectively.
Asunto(s)
Antiinfecciosos/química , Glucosamina/química , Glucosa/química , Sulfametoxazol/química , Tampones (Química) , Concentración de Iones de Hidrógeno , TemperaturaRESUMEN
A stability-indicating high-performance liquid-chromatographic (HPLC) assay has been developed for amphotericin B (AmB) in a paste, containing AmB, tobramycin (or gentamicin) sulphate, colistin sulphate, liquid paraffin and Orabase. Extraction of AmB was performed by partitioning the antibiotic between N,N-dimethylformamide (DMF) and cyclohexane, which led to precipitation of the polymeric materials and extraction of the liquid paraffin into the cyclohexane and AmB into the DMF. Analysis by HPLC of the latter layer gave a linear relationship between concentration and peak area response for the AmB over the range 5.0 x 10(-4) to 7.5 x 10(-3)% (w/v) (r = 0.9995) with a relative standard deviation of +/- 1.46% (n = 8). The efficiency of extraction was 1006 +/- 2.4% (n = 5).
Asunto(s)
Anfotericina B/análisis , Antifúngicos/análisis , Cromatografía Líquida de Alta Presión/métodos , Pomadas/química , ColoidesRESUMEN
The chemical reaction between procainamide hydrochloride and glucose following admixture to glucose infusion has been investigated. Substantial amounts (10-15% after 10 h at room temperature) of the procainamide is lost with the formation of a mixture of the corresponding alpha- and beta-glucosylamines. The chemical identity of the latter compounds was confirmed by 13C and 1H nuclear magnetic resonance spectroscopy.
Asunto(s)
Glucosa/química , Procainamida/química , Cromatografía Líquida de Alta Presión , Deuterio , Interacciones Farmacológicas , Glucosamina/química , Glucosamina/metabolismo , Glucosa/administración & dosificación , Concentración de Iones de Hidrógeno , Hidrólisis , Infusiones Intravenosas , Espectroscopía de Resonancia Magnética , Procainamida/administración & dosificaciónRESUMEN
Analytical methods have been developed which enable phenylmercuric nitrate, mercuric ion and diphenylmercury to be measured in sulphacetamide drops. Application of these methods demonstrate that during heat sterilization of both 10 and 30% sulphacetamide drops containing phenylmercuric nitrate, together with disodium edetate and sodium metabisulphite, there is a 20-30% overall loss of phenylmercuric nitrate. This loss occurs mainly due to the phenylmercuric ion establishing an equilibrium with equimolar amounts of mercuric ion and diphenylmercury.
Asunto(s)
Fungicidas Industriales/química , Compuestos de Fenilmercurio/química , Sulfacetamida/química , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Calefacción , Mercurio/química , Soluciones Oftálmicas , EsterilizaciónAsunto(s)
Compuestos de Benzalconio/análisis , Celulosa/análogos & derivados , Metilcelulosa/análogos & derivados , Soluciones Oftálmicas/química , Pilocarpina/química , Alcohol Polivinílico/química , Celulosa/química , Combinación de Medicamentos , Derivados de la Hipromelosa , Estándares de Referencia , Espectrofotometría UltravioletaRESUMEN
The stability following heat sterilization (121 degrees C for 15 min) of phenylmercuric (PM) nitrate in the presence of disodium edetate at pH values 5-8 has been investigated by both high-performance liquid chromatography (HPLC) and atomic absorption spectroscopy (AAS). A stability-indicating HPLC method involving formation of the diethylamine-dithiocarbamate complexes of phenylmercuric and mercuric ions was found to suffer a pH-dependent interference from disodium edetate. A second method was therefore also employed involving selective extraction into diethylether of the phenylmercuric ion followed by HPLC of the piperidinedithiocarbamate complex with concomitant analysis of the unextracted mercuric ion by AAS using the cold-vapour technique. An HPLC method was also developed for benzene in the degraded mixtures. The application of these methods to autoclaved solutions containing PM nitrate and disodium edetate demonstrates that under the conditions of heat sterilization the phenylmercuric ion is degraded to mercuric ion and benzene to the extent of 15% at pH 8, 80% at pH 7 and completely degraded at pH 5 and 6.
Asunto(s)
Ácido Edético/química , Soluciones Oftálmicas , Compuestos de Fenilmercurio/química , Esterilización , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Calor , Humanos , Concentración de Iones de Hidrógeno , Espectrofotometría Atómica , Australia OccidentalRESUMEN
High-performance liquid chromatographic (HPLC) assays have been developed for phenylmercuric nitrate and mercuric ions in the presence of disodium edetate. Application of these methods to neomycin eye drops of the Pharmaceutical Codex and Australian Pharmaceutical Formulary, which contain both phenylmercuric nitrate and disodium edetate, show that edetate promotes approximately 20% decomposition of the phenylmercuric nitrate in the drops of the Pharmaceutical Codex but little in the drops of the Australian Pharmaceutical Formulary during sterilization by the recommended method. The reason for the stability of the organomercurial in the Australian product was determined as being due to the presence of sodium chloride in the formulation.
Asunto(s)
Ácido Edético/química , Neomicina/química , Compuestos de Fenilmercurio/química , Esterilización , Cromatografía Líquida de Alta Presión , Calor , Humanos , Soluciones OftálmicasRESUMEN
A high-performance liquid chromatographic assay for phenylmercuric nitrate in the presence of zinc ions has been developed. Application of the assay to zinc sulphate and zinc sulphate and adrenaline drops before and after autoclaving demonstrates that the phenylmercuric nitrate is chemically degraded in the zinc sulphate and adrenaline drops.
Asunto(s)
Soluciones Oftálmicas/análisis , Compuestos de Fenilmercurio/química , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Epinefrina , Compuestos de Fenilmercurio/análisis , Sulfatos , Zinc , Sulfato de ZincRESUMEN
The degradation of phenylmercuric nitrate in the presence of sodium metabisulphite in eye drop formulations has been investigated using a stability-indicating high-performance liquid chromatographic (HPLC) method. HPLC methods have been developed for the quantitation of the principal degradation products (diphenyl-mercury, benzenesulphonic acid and benzenesulphinic acid) and a mechanism is proposed for their formation. The pharmaceutical significance of the interaction is briefly discussed.
Asunto(s)
Compuestos de Fenilmercurio/análisis , Sulfitos/análisis , Bencenosulfonatos/análisis , Fenómenos Químicos , Química , Cromatografía Líquida de Alta Presión , Calor , Cinética , Soluciones Oftálmicas , Espectrofotometría Ultravioleta , EsterilizaciónRESUMEN
Histamine acid phosphate (HAP) solutions are used in tests for asthma and also as positive controls in general allergenic testing. Previously these solutions have been sterilized, if at all, by filtration, thus limiting the shelf-life of the preparation and introducing some degree of uncertainty in their use. It is shown here that HAP solutions can be sterilized successfully by heating in an autoclave with little degradation and that subsequent storage of autoclaved solutions indicates a minimum shelf-life of 4 months.
Asunto(s)
Histamina/análogos & derivados , Esterilización , Fenómenos Químicos , Química Física , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Calor , Espectrofotometría Ultravioleta , Factores de TiempoRESUMEN
The British Pharmacopoeial test for assessing the solution rate of slow lithium carbonate tablets has been evaluated using 'controlled release' tablets containing 400 mg of lithium carbonate. No significant differences in lithium release were found when the volume of media used in the test was reduced from 250 ml to 200 ml, the final stage of the test in pH 6.8 phosphate buffer reduced from 5 to 3 h, the number of tablets in each thimble reduced from three to one, or the prescribed phosphate buffers replaced with phthalate and Tris, respectively. A four-fold increased concentration of phosphate in the phosphate buffers used resulted in a significant retardation in lithium solution rate. This was not attributable to an ionic strength effect but possibly to the formation of trilithium phosphate at the interface. Dissolution studies using the USP Basket Method showed a significantly slower release rate of one tablet into 900 ml of phosphate buffer compared with Tris buffer. This difference was markedly increased when three tablets were investigated in 200 ml of similar media. These differences were considered to be due to the formation of the much less soluble trilithium phosphate in the phosphate buffers.
Asunto(s)
Litio/análisis , Preparaciones de Acción Retardada , Concentración de Iones de Hidrógeno , Cinética , Carbonato de Litio , Farmacopeas como Asunto , Solubilidad , Soluciones , Reino UnidoRESUMEN
Intrinsic dissolution rate studies were carried out on lithium carbonate discs that were prepared with the disc in a component on the final support. This overcame the problem of further handling of the fragile discs. Dissolution media employed were similar to those used for the routine evaluation of lithium carbonate dosage forms. Linear dissolution rate profiles were found in simulated gastric fluid (SGF), Tris buffer and water. Data in SGF and water showed positive intercepts with the Levich model. The dissolution process of lithium carbonate was considered to be complex. Dissolution profiles in simulated intestinal fluid (SIF) containing phosphate showed a marked initial curvature and a subsequent reduced dissolution rate. This was due to the precipitation of trilithium phosphate onto the disc. Dissolution rate studies on lithium carbonate dosage forms could be invalidated where a phosphate buffer system has been used.
Asunto(s)
Litio , Química Farmacéutica , Carbonato de Litio , Solubilidad , Soluciones , Espectrofotometría InfrarrojaRESUMEN
The influence of a range of nine anti-inflammatory drugs on the octan-1-ol aqueous phosphate buffer pH 7.4 apparent partition coefficients of propranolol and oxprenolol has been examined. All produced a change in the apparent partition coefficient which can be explained in terms of partitioning of hydrophobic ion-pairs formed between the ionic anti-inflammatory compound and the protonated cationic drug.