RESUMO
The Vilsmeier and the Arndt-Eistert reactions have been employed for the synthesis of 1-phenyl-2-chloroindole-3-acetic acid (4). The antiinflammatory activity of 2-chloroindole-3-carboxylic acid (1), 1- methyl-2-chloroindole-3-carboxylic acid (2), 1-phenyl-2-chloroindole-3-carboxylic acid (3), and 4 was compared with the activity of indomethacin in the carrageenin rat edema. The best results are given by compounds 1 and 2 bearing H or CH3 at position 1 and COOH at position 3.
Assuntos
Anti-Inflamatórios/síntese química , Indóis/síntese química , Animais , Anti-Inflamatórios/toxicidade , Indóis/farmacologia , Indóis/toxicidade , Dose Letal Mediana , Masculino , Camundongos , Ratos , Fatores de TempoRESUMO
The antimitotic properties associated with the bis (2-chloroethyl) amino group are well known, a number of compounds bearing this group being of therapeutic interest. The choice of a suitable supporting moiety for this group is important. Our experiments on a butyrophenone derivative, ketocaine, which possesses local anesthetic activity, showed that this drug is able to modify the oxygen consumption by tissues with prevailing anaerobic metabolism and to inhibit the mitotic activity of human lymphocytes in culture stimulated by phytohemagglutinin. These observations prompted us to prepare compounds by the general formula reported in Tables I and II. All compounds were tested in mice implanted i.p. with 10(6) Ehrlich ascites tumour cells. After 24 h the animals were treated with a single dose of the compound. The antitumor activity was correlated with: position (2, 4) and length (n = 0-2) of the chain with carbonyl group; presence (R' = H, ND2) and position (2, 4) of nitro group; monofunzional or bifunzional compound. Some of these show a potent antitumor activity.
Assuntos
Alquilantes/farmacologia , Antineoplásicos/farmacologia , Butirofenonas/farmacologia , Animais , Feminino , Camundongos , Relação Estrutura-AtividadeRESUMO
The synthesis of two nitrogen mustard derivatives (VIII and IX) related to the well-known local anesthetic ketocaine (III) is reported. These compounds were tested in mice implanted with Ehrlich ascites tumor cells, and the antitumor activity was compared with that of two previously synthesized analogues (I and II) lacking the nitro group and with that of doxorubicin. The monofunctional compound IX was inactive, but the bifunctional compound VIII showed potent antitumor activity (%T/C greater than 254 at 20 mg/kg).
Assuntos
Antineoplásicos/síntese química , Butirofenonas/síntese química , Compostos de Mostarda Nitrogenada , Compostos de Mostarda Nitrogenada/síntese química , Animais , Antineoplásicos/farmacologia , Butirofenonas/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/metabolismo , Células Cultivadas , Fenômenos Químicos , Química , Feminino , Camundongos , Neoplasias/metabolismo , Compostos de Mostarda Nitrogenada/farmacologia , Consumo de OxigênioRESUMO
A reversed-phase HPLC method is proposed for the separation of five liquorice triterpenoids, 18 beta glycyrrhetic acid (beta GA), 18 alpha glycyrrhetic acid (alpha GA), 24-hydroxy-18 beta-glycyrrhetic acid (24-OH-beta GA), alpha and beta liquiritic acid (alpha and beta LA), with potentially different biological activities. The method has been developed by studying the influence of the type of stationary phase, pH, amine modifier and organic modifier on the resolution of the five compounds. The optimized chromatographic conditions were then successfully applied to the analysis of alpha- and beta-GA in pharmaceutical preparations (toothpaste and creams) on a reversed-phase Phenomenex Ultracarb 5 ODS (30) column (150 x 4.6 mm i.d.), using as the mobile phase acetonitrile-THF-0.010 M dioctylammonium phosphate buffer (pH 6.5) (25:20:55, v/v/v) at a flow-rate of 0.8 ml min-1. SPE methods with diolic and C18 sorbents were developed to isolate and concentrate the analytes and to enhance the sensitivity for the determination of alpha-GA as an impurity in the beta-GA preparations. The method was found to be reliable and suitable for the quality control of beta-GA preparations.
Assuntos
Glycyrrhiza/química , Plantas Medicinais , Triterpenos/análise , Anti-Infecciosos/análise , Cromatografia Líquida de Alta Pressão , Ácido Glicirretínico/análise , Concentração de Íons de Hidrogênio , Controle de Qualidade , Saponinas/isolamento & purificação , SolubilidadeRESUMO
Solid-phase extraction (SPE) using C-18, diol and ion-exchange sorbents followed by UV spectrophotometric (conventional and derivative mode) assay was applied to the analysis of basic, acidic and neutral drugs commercially available in creams. A representative set of drugs (promethazine, chlorhexidine, benzydamine, ketoprofen, ibuprofen, fentiazac, piroxicam, fluorouracil, crotamiton and hydrocortisone acetate) was selected, and for each drug the appropriate SPE conditions (adsorption, washing and elution) were investigated to obtain a practical and reliable sample clean-up. It was shown that the developed SPE procedures were capable of removing interfering cream components (excipients including preservatives) allowing accurate spectrophotometric analyses to be performed. In some applications, derivative spectrophotometry was advantageous over the conventional absorption mode with respect to higher selectivity and versatility.
Assuntos
Preparações Farmacêuticas/análise , Preparações Farmacêuticas/isolamento & purificação , Espectrofotometria UltravioletaRESUMO
A simple second-order derivative spectrophotometric method was developed for the selective determination of flucytosine (an antimycotic drug) in the presence of 5-fluorouracil (a cytotoxic agent), its synthetic precursor and degradation product. Traces of 5-fluorouracil in flucytosine were also determined by derivative UV spectroscopy; flucytosine was removed by a selective solid-phase extraction (SPE) procedure using a strong cation-exchange sorbent. The spectrophotometric methods were applied successfully to the quality control of commercial dosage forms of flucytosine and the results were compared with those obtained by a HPLC procedure (cyano column) developed as a reference method.
Assuntos
Flucitosina/análise , Fluoruracila/análise , Cromatografia Líquida de Alta Pressão , Formas de Dosagem , Controle de Qualidade , Espectrofotometria UltravioletaRESUMO
The use of 2-chloro-6,7-dimethoxy-3-quinolinecarboxaldehyde as a fluorogenic labelling reagent in pre-column derivatization for the HPLC separation of chlorophenols has been investigated. The compound reacts (50 min at 110 degrees C) with 2- and 4-chlorophenols to give fluorescent ethers that can be separated by reversed-phase HPLC and detected at lambda exc = 360 nm, lambda em = 500 nm. The experimental conditions for derivatization and chromatographic separation are discussed. Applications for the determination of chlorocresol (4-chloro-3-cresol) and chloroxylenol (4-chloro-3,5-xylenol) in pharmaceutical formulations (creams, ointments) are described.
Assuntos
Cresóis/análise , Xilenos/análise , Calibragem , Cromatografia Líquida de Alta Pressão , Corantes Fluorescentes , Espectroscopia de Ressonância Magnética , Pomadas , Quinolinas , Espectrometria de Fluorescência , Espectrofotometria InfravermelhoRESUMO
Derivative UV spectroscopy and high performance liquid chromatography (HPLC) were applied to the determination of angiotensin-converting enzyme (ACE) inhibitors in their pharmaceutical dosage forms. For spectrophotometric determinations, the more appropriate derivative order was selected for each drug: ramipril (third-order), benazepril (second-order), enalapril maleate (second-order), lisinopril (first- and second-order) and quinapril (first-order). Reverse phase HPLC procedures (ODS column) were developed able to provide a single, symmetric peak for each drug; mixtures A-B, where A is 20 mM sodium heptansulphonate (pH 2.5) and B is acetonitrile-THF (95:5 v/v), proved to be suitable mobile phases to obtain selective separations of the cited ACE inhibitors. At ambient temperature, a low pH value (2.5) was found to be critical to avoid peak splitting and band broadening.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/análise , Calibragem , Cápsulas , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Espectrofotometria Ultravioleta , ComprimidosRESUMO
A supercritical fluid extraction (SFE) method was developed for the isolation of imidazole antimycotic drugs (miconazole, econazole, clotrimazole and bifonazole) from cream preparations. The SFE process involved static (1 min) and dynamic (4 min) extraction steps using pure and 10% methanol modified carbon dioxide. The SFE step was then followed by derivative UV spectrophotometric analysis. The method proved to be suitable for quality control assays of the examined antimycotics in commercial cream formulations.
Assuntos
Antifúngicos/análise , Imidazóis/análise , Pomadas/química , Miconazol , Pressão , Solubilidade , Espectrofotometria Ultravioleta , Temperatura , Fatores de TempoRESUMO
Ethacrynic acid and its methyl ester are proposed as useful pre-chromatographic derivatization reagents for the HPLC analysis (UV detection) of reduced glutathione (GSH) and L-cysteine. The optimum experimental conditions for the thiol derivatization, the removal of the excess reagent by liquid-liquid or solid-phase extraction and the reversed-phase chromatographic separations of the thiol adducts were investigated. The method was applied to the HPLC determination of GSH and L-cysteine in commercial formulations and proved to be suitable for the HPLC determination of oxidized glutathione (GSSG) after reduction to GSH using dithiothreitol (DTT).
Assuntos
Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão , Cisteína/análise , Ácido Etacrínico/química , Glutationa/análise , Calibragem , Ditiotreitol/química , Oxirredução , Pós , Estereoisomerismo , ComprimidosRESUMO
A reversed phase liquid chromatographic (HPLC) method is proposed for the determination of sodium fusidate, a steroid antibiotic, in a commercial ointment using three different detectors: a) fluorescence detector, after a preliminary derivatization with 2-bromoacetyl-6-methoxynaphthalene (Br-AMN), b) UV detection and c) evaporative light scattering detector (ELSD). Fluorescent derivatization was applied directly to the diluted sample, without any purification, whilst UV and ELSD detectors involved a preliminary liquid-liquid extraction procedure to obtain accurate analysis data.
Assuntos
Antibacterianos/análise , Ácido Fusídico/análise , Cromatografia Líquida de Alta Pressão , Fluorescência , Luz , Espalhamento de Radiação , Raios UltravioletaRESUMO
A simple difference spectrophotometric method has been developed for the selective and rapid determination of minoxidil in pharmaceutical formulations. The method is based on the characteristic modifications of the minoxidil UV spectrum induced by pH changes; a difference spectrum can be obtained and the absorbance A282.8 or the absorbance difference delta A = (A282.8-A259.2) can be used for the selective drug quantitation. As an alternative, a derivative second-order spectrophotometric method was also developed. The spectrophotometric methods were applied to the quality control of commercial minoxidil dosage forms and the results were comparable with those obtained by a reference HPLC procedure.
Assuntos
Minoxidil/análise , Cromatografia Líquida de Alta Pressão , Soluções , Espectrofotometria Ultravioleta , ComprimidosRESUMO
Derivative and difference spectrophotometric methods are described for the direct simultaneous analysis of combinations of Trimethoprim with sulfonamide drugs (sulfadiazine, sulfamethoxazole, sulfamethoxypyridazine) in commercial dosage forms. The more advantageous approach (derivative and difference mode) is suggested for each binary mixture. The assay results are compared with those obtained by a new chromatographic (HPLC) method, involving a C-18 column and a mobile phase (pH 6.5) containing 1.8 diaminooctane as amine modifier and sodium heptansulfonate as ion pairing agent.
Assuntos
Sulfadiazina/análise , Sulfametoxazol/análise , Sulfametoxipiridazina/análise , Trimetoprima/análise , Cápsulas , Cromatografia Líquida de Alta Pressão/métodos , Combinação de Medicamentos , Concentração de Íons de Hidrogênio , Espectrofotometria Ultravioleta/métodos , ComprimidosRESUMO
The authors synthesized the title compounds as analogues of previously prepared potential antiphlogistic agents. Starting from appropriate carbonyl compound and alpha-metallated phenylacetic acid the diastereomeric racemate pairs were obtained; they were separated, attributed to erythro/threo-configuration by NMR and finally resolved. The potassium salts of the enantiomers were tested for analgesic and antiinflammatory activity, as well as for acute toxicity. Their action in the carrageenan test has been found to be stereoselective, but relatively poor or of briefly lastening.