Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mikrochim Acta ; 188(3): 103, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646401

RESUMO

Molybdenum disulfide (MoS2) surface functionalization was performed with a catechol-containing polymer sodium alginate (SA) and dopamine (DA) through simultaneous MoS2 exfoliation and self-polymerization of DA. The MoS2/SA-PDA nanocomposite was characterized using spectroscopic, microscopic, and electroanalytical techniques to evaluate its electrocatalytic performance. The electrocatalytic behavior of the MoS2/SA-PDA nanocomposite modified electrode for the detection of acebutolol (ACE), a cardio-selective ß-blocker drug was explored  through cyclic voltammetric and differential pulse voltammetric techniques. The influence of scan rate, concentration, and pH value on the oxidation peak current of ACE was investigated  to optimize the deducting condition. The electrochemical activity of the MoS2/SA-PDA nanocomposite electrode was attributed to the existence of reactive functional groups being contributed from SA, PDA, and MoS2 exhibiting a synergic effect. The MoS2/SA-PDA nanocomposite modified electrode exhibits admirable electrocatalytic activity with a wide linear response range (0.009 to 520 µM), low detection limit (5 nM), and high sensitivity (0.354 µA µM-1 cm-2) also in the presence of similar (potentially interfering) compounds. The fabricated MoS2/SA-PDA nanocomposite modified electrode can be useful for the detection of ACE in pharmaceutical analysis.


Assuntos
Acebutolol/análise , Antagonistas de Receptores Adrenérgicos beta 1/análise , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Nanocompostos/química , Acebutolol/sangue , Acebutolol/química , Acebutolol/urina , Antagonistas de Receptores Adrenérgicos beta 1/sangue , Antagonistas de Receptores Adrenérgicos beta 1/química , Antagonistas de Receptores Adrenérgicos beta 1/urina , Alginatos/química , Técnicas Biossensoriais/métodos , Dissulfetos/química , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Indóis/química , Limite de Detecção , Molibdênio/química , Oxirredução , Polímeros/química , Reprodutibilidade dos Testes
2.
Biochem Pharmacol ; 171: 113731, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783011

RESUMO

Stereoselectivity is well described for receptor binding and enzyme catalysis, but so far has only been scarcely investigated in carrier-mediated membrane transport. We thus studied transport kinetics of racemic (anti)adrenergic drugs by the organic cation transporters OCT1 (wild-type and allelic variants), OCT2, OCT3, MATE1, and MATE2-K with a focus on stereospecificity. OCT1 showed stereoselective uptake with up to 2-fold higher vmax over their corresponding counterpart enantiomers for (R,R)-fenoterol, (R,R)-formoterol, (S)-salbutamol, (S)-acebutolol, and (S)-atenolol. Orciprenaline and etilefrine were also transported stereoselectively. The Km was 2.1-fold and 1.5-fold lower for the (S,S)-enantiomers of fenoterol and formoterol, while no significant difference in Km was seen for the other aforementioned drugs. Common OCT1 variants showed similar enantiopreference to wild-type OCT1, with a few notable exceptions (e.g. a switch in enantiospecificity for fenoterol in OCT1*2 compared to the wild-type). Other cation transporters showed strong differences to OCT1 in stereoselectivity and transport activity: The closely related OCT2 displayed a 20-fold higher vmax for (S,S)-fenoterol compared to (R,R)-fenoterol and OCT2 and OCT3 showed 3.5-fold and 4.6-fold higher vmax for the pharmacologically active (R)-salbutamol over (S)-salbutamol. MATE1 and MATE2-K generally mediated transport with a higher capacity but lower affinity compared to OCT1, with moderate stereoselectivity. Our kinetic studies showed that significant stereoselectivity exists in solute carrier-mediated membrane transport of racemic beta-adrenergic drugs with surprising, and in some instances even opposing, preferences between closely related organic cation transporters. This may be relevant for drug therapy, given the strong involvement of these transporters in hepatic and renal drug elimination.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos/farmacologia , Proteínas de Transporte de Cátions Orgânicos/agonistas , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Acebutolol/química , Acebutolol/metabolismo , Acebutolol/farmacologia , Agonistas Adrenérgicos/química , Agonistas Adrenérgicos/metabolismo , Antagonistas Adrenérgicos/química , Antagonistas Adrenérgicos/metabolismo , Atenolol/química , Atenolol/farmacologia , Transporte Biológico , Fenoterol/química , Fenoterol/metabolismo , Fenoterol/farmacologia , Fumarato de Formoterol/química , Fumarato de Formoterol/metabolismo , Fumarato de Formoterol/farmacologia , Células HEK293 , Humanos , Cinética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 1 de Cátions Orgânicos/agonistas , Transportador 1 de Cátions Orgânicos/antagonistas & inibidores , Transportador 1 de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico/agonistas , Transportador 2 de Cátion Orgânico/antagonistas & inibidores , Transportador 2 de Cátion Orgânico/metabolismo , Estereoisomerismo
3.
Molecules ; 24(20)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614604

RESUMO

A wooden stick coated with a novel graphene-based nanocomposite (Graphene oxide/polyethylene glycol (GO/PEG)) is introduced and investigated for its efficacy in solid phase microextraction techniques. The GO/PEG-stick was prepared and subsequently applied for the extraction of ß-blockers, acebutolol, and metoprolol in human oral fluid samples, which were subsequently detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). Experimental parameters affecting the extraction protocol including sample pH, extraction time, desorption time, appropriate desorption solvent, and salt addition were optimized. Method validation for the detection from oral fluid samples was performed following FDA (Food and Drug Administration) guidelines on bioanalytical method validation. Calibration curves ranging from 5.0 to 2000 nmol L-1 for acebutolol and 25.0 to 2000 nmol L-1 for metoprolol were used. The values for the coefficient of determination (R2) were found to be 0.998 and 0.996 (n = 3) for acebutolol and metoprolol, respectively. The recovery of analytes during extraction was 80.0% for acebutolol and 62.0% for metoprolol, respectively. The limit of detections (LODs) were 1.25, 8.00 nmol L-1 for acebutolol and metoprolol and the lower limit of quantifications (LLOQ) were 5.00 nmol L-1 for acebutolol and 25.0 nmol L-1 for metoprolol. Validation experiments conducted with quality control (QC) samples demonstrated method accuracy between 80.0% to 97.0% for acebutolol and from 95.0% to 109.0% for metoprolol. The inter-day precision for QC samples ranged from 3.6% to 12.9% for acebutolol and 9.5% to 11.3% for metoprolol. Additionally, the GO/PEG-stick was demonstrated to be reusable, with the same stick observed to be viable for more than 10 extractions from oral fluid samples.


Assuntos
Acebutolol/isolamento & purificação , Antagonistas Adrenérgicos beta/isolamento & purificação , Metoprolol/isolamento & purificação , Microextração em Fase Sólida/métodos , Acebutolol/química , Antagonistas Adrenérgicos beta/química , Líquidos Corporais/química , Cromatografia Líquida , Grafite/química , Humanos , Limite de Detecção , Metoprolol/química , Boca/química , Nanocompostos/química , Polietilenoglicóis/química , Espectrometria de Massas em Tandem
4.
J Sep Sci ; 42(5): 1077-1087, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30659744

RESUMO

In order to have deep insights into the mechanisms of enantiomer affinity pattern in both aqueous and non-aqueous systems, an approach combining capillary electrophoresis and molecular modeling was undertaken. A chiral ß-blocker; acebutolol, was enantioseparated in aqueous capillary electrophoresis and non-aqueous capillary electrophoresis using two anionic ß-cyclodextrin derivatives. The enantiomer affinity pattern of acebutolol was found to be opposite when an aqueous background electrolyte was replaced with non-aqueous background electrolyte in the presence of heptakis(2,3-di-O-acetyl-6-sulfo)-ß-cyclodextrin but remained the same in the presence of heptakis(2,3-di-O-methyl-6-sulfo)-ß-cyclodextrin. Molecular docking of acebutolol into two ß-cyclodextrin derivatives indicated two distinct binding modes called 'up' and 'down' conformations. After structure optimization by molecular dynamics and energy minimization, both enantiomers of acebutolol were preferred to the 'up' conformation with heptakis(2,3-di-O-methyl-6-sulfo)-ß-cyclodextrin while 'down' conformation with heptakis(2,3-di-O-acetyl-6-sulfo)-ß-cyclodextrin. The further calculation of the complex energy with solvent effect indicated that heptakis(2,3-di-O-acetyl-6-sulfo)-ß-cyclodextrin had higher affinity to S-acebutolol than R-acebutolol in non-aqueous capillary electrophoresis while it showed better binding to R-acebutolol in aqueous capillary electrophoresis. However, the heptakis(2,3-di-O-methyl-6-sulfo)-ß-cyclodextrin bound better to R-acebutolol in both aqueous and non-aqueous capillary electrophoresis, implying that the binding mode played more important role in chiral separation of heptakis(2,3-di-O-methyl-6-sulfo)-ß-cyclodextrin while the solvent effect had prevailing impact on heptakis(2,3-di-O-acetyl-6-sulfo)-ß-cyclodextrin.


Assuntos
Acebutolol/química , Antagonistas Adrenérgicos beta/química , Ciclodextrinas/química , Metanol/química , Água/química , Acebutolol/isolamento & purificação , Antagonistas Adrenérgicos beta/isolamento & purificação , Ânions/química , Ânions/isolamento & purificação , Ciclodextrinas/isolamento & purificação , Eletrólitos/química , Eletroforese Capilar , Modelos Moleculares , Conformação Molecular , Estereoisomerismo
5.
Environ Sci Pollut Res Int ; 23(3): 2521-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26423291

RESUMO

This study investigated the reaction kinetics and the transformation by-products of acebutolol during aqueous chlorination. Acebutolol is one of the commonly used ß-blockers for the treatment of cardiovascular diseases. It has been frequently detected in the aquatic environment. In the kinetics study, the second-order rate constant for the reaction between acebutolol and chlorine (k app) was determined at 25 ± 0.1 °C. The degradation of acebutolol by free available chlorine was highly pH dependence. When the pH increased from 6 to 8, it was found that the k app for the reaction between acebutolol and free available chlorine was increased from 1.68 to 11.2 M(-1) min(-1). By comparing with the reported k app values, the reactivity of acebutolol toward free available chlorine was found to be higher than atenolol and metoprolol but lower than nadolol and propranolol. Characterization of the transformation by-products formed during the chlorination of acebutolol was carried out using liquid chromatography-quadrupole time-of-flight high-resolution mass spectrometry. Seven major transformation by-products were identified. These transformation by-products were mainly formed through dealkylation, hydroxylation, chlorination, and oxidation reactions.


Assuntos
Acebutolol/química , Antagonistas de Receptores Adrenérgicos beta 1/química , Anti-Hipertensivos/química , Poluentes Químicos da Água/química , Purificação da Água , Antagonistas Adrenérgicos beta/química , Atenolol/química , Cloro/química , Cromatografia Líquida , Halogenação , Cinética , Espectrometria de Massas , Oxirredução , Propranolol/química , Água/química
6.
J AOAC Int ; 98(1): 46-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25857877

RESUMO

Two therapeutically active compounds from the group of ß-blockers, acebutolol (AC) and alprenolol (AL), in solid form were subjected to ionizing radiation emitted by a beam of high energy electrons from an accelerator with a standard sterilization dose of 25 kGy and in higher doses of 50-400 kGy. The effects of irradiation were detected by chromatographic methods (TLC, HPLC) and a hyphenated method (HPLC/MS/MS). No significant changes in the physicochemical properties of both compounds studied irradiated with 25 kGy were noted, but upon irradiation with the highest dose (400 kGy) the loss of AC and AL content determined by HPLC was 2.79 and 9.12%, respectively. The product of AC decomposition and the two products of AL decomposition were separated and identified by HPLC/MS/MS. It has been established that radiodegradation of AC and AL takes place by oxidation, leading to formation of the products of radiolysis, most probably alcohol derivatives of the ß-blockers studied. The additional product that appears on radiodegradation of AL is probably formed as a result of two simultaneous reactions: oxidation and CH2 group elimination.


Assuntos
Acebutolol/química , Alprenolol/química , Cromatografia Líquida de Alta Pressão/métodos , Radiação Ionizante , Espectrometria de Massas em Tandem/métodos
7.
Eur J Pharm Biopharm ; 84(1): 183-91, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23291047

RESUMO

The interaction of propranolol and acebutolol with biological membranes was assessed in the present work by using a range of biophysical techniques and liposomes, as membrane mimetic models. Liposomes were made of zwitterionic phosphatidylcholines and experiments were performed at physiologic pH and at various membrane physical states (gel, ripple and fluid phases). Fluorescence techniques were used to study the partition coefficient of ß-blockers, the influence of drugs on membrane fluidity and the drugs-membrane binding. Moreover, small and wide angle X-ray scattering techniques were used to evaluate the ß-blockers effect on long range bilayer order and hydrocarbon chain packing. The gathered results highlighted the importance of electrostatic interactions between propranolol and acebutolol with membranes. Furthermore, both ß-blockers exhibited a membrane-fluidizing effect and the capacity to disturb the membrane organization. In general, propranolol unveiled a more pronounced effect on membrane fluidity and structure than acebutolol. In the current study, the obtained results were also correlated with the cardioprotective properties of the ß-blockers studied.


Assuntos
Acebutolol/metabolismo , Antagonistas Adrenérgicos beta/metabolismo , Membranas Artificiais , Propranolol/metabolismo , Acebutolol/química , Antagonistas Adrenérgicos beta/química , Fenômenos Biofísicos/efeitos dos fármacos , Fenômenos Biofísicos/fisiologia , Membrana Celular , Lipossomos , Propranolol/química , Difração de Raios X
8.
Eur J Pharm Sci ; 48(1-2): 291-300, 2013 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-23178441

RESUMO

The solubility vs. pH profiles of five ionizable drugs of different nature (a monoprotic acid, a monoprotic base, a diprotic base and two amphoteric compounds showing a zwitterionic species each one) have been determined through two different methodologies: the classical shake-flask (S-F) and the potentiometric Cheqsol methods using in both instances the appropriate Henderson-Hasselbalch (H-H) or derived relationships. The results obtained independently from both approaches are consistent. A critical revision about the influence of the electrolyte used as buffering agent in the S-F method on the obtained solubility values is also performed. Thus, some deviations of the experimental points with respect the H-H profiles can be attributed to specific interactions between the buffering electrolyte and the drug due to the hydrotrophic character of citric and lactic acids. In other cases, the observed deviations are independent of the buffers used since they are caused by the formation of new species such as drug aggregates (cefadroxil) or the precipitation of a salt from a cationic species of the analyzed compound (quetiapine).


Assuntos
Acebutolol/química , Cefadroxila/química , Dibenzotiazepinas/química , Parabenos/química , Sulfadimetoxina/química , Soluções Tampão , Concentração de Íons de Hidrogênio , Preparações Farmacêuticas/química , Potenciometria , Fumarato de Quetiapina , Solubilidade
9.
J Mol Model ; 18(9): 4491-501, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22643977

RESUMO

The aim of this study is to investigate the active components of representative drugs for blood pressure regulation by applying quantum mechanical computer codes and comparison of the same for the sake of obtaining knowledge about the properties associated with the electronic structure of given molecules. The study included three well-known, but not theoretically investigated enough, active components of ß-blockers: acebutolol, metoprolol and atenolol. The results are in agreement with the experimental data and were used for initial assumptions concerning the degradation of these compounds.


Assuntos
Antagonistas Adrenérgicos beta/química , Antagonistas Adrenérgicos beta/farmacologia , Simulação por Computador , Acebutolol/química , Acebutolol/farmacologia , Atenolol/química , Atenolol/farmacologia , Dureza , Humanos , Hidrocarbonetos Aromáticos/química , Espectroscopia de Ressonância Magnética , Metoprolol/química , Metoprolol/farmacologia , Modelos Moleculares , Conformação Molecular , Eletricidade Estática
10.
Magn Reson Chem ; 49(5): 284-90, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21491484

RESUMO

The ß-blockers are important drugs and decades of clinical experience proved their high medical status. However, to the best of our knowledge, there is no complete assignment of (1)H and (13)C NMR resonances of popular representatives: acebutolol, alpenolol, pindolol, timolol and propranolol and the published NMR data on carvedilol and atenolol are incorrect. Therefore, (1)H and (13)C NMR spectroscopy was applied for the characterization of a series of ß-adrenolytics: carvedilol (1), pindolol (2), alprenolol (3), acebutolol (4), atenolol (5), propranolol (6) and timolol (7). Two-dimensional NMR experiments (COSY, HMQC, HMBC, NOESY) allowed the unequivocal assignment of (1)H and (13)C spectra for solution (DMSO-d(6) ). Salts and bases can be easily distinguished based on (13)C chemical shifts which are within 65.0-65.5 ppm (OC2) and 46.9-47.0 (NC3) for hydrochlorides and larger, ca. 68.4 ppm (OC2) and 50.3-52.6 (NC3) for bases. NMR data of 1-7 should be included in pharmacopoeias.


Assuntos
Antagonistas Adrenérgicos beta/análise , Isótopos de Carbono/análise , Prótons , Acebutolol/análise , Acebutolol/química , Ácidos/química , Antagonistas Adrenérgicos beta/química , Álcalis/química , Alprenolol/análise , Alprenolol/química , Atenolol/análise , Atenolol/química , Carbazóis/análise , Carbazóis/química , Isótopos de Carbono/química , Carvedilol , Ressonância Magnética Nuclear Biomolecular , Pindolol/análise , Pindolol/química , Propanolaminas/análise , Propanolaminas/química , Propranolol/análise , Propranolol/química , Timolol/análise , Timolol/química
11.
Colloids Surf B Biointerfaces ; 82(2): 581-7, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-21071185

RESUMO

The complex formed due to the interaction of the amphiphilic betablocker acebutolol with fibrinogen in a buffer solution (50mN glycine, pH of 8.5) has been investigated using a multipronged physicochemical approach. Differential scanning calorimetry measurements of the complexes have shown no reversibility of thermal denaturation as indicated by the three observed peaks and the opposite role that acebutolol plays in the folding different domains of the fibrinogen molecule and the stability of such domains. While circular dichroism measurements have revealed that interaction of acebutolol with fibrinogen affects the protein secondary structure to a different extent depending on the temperature and drug concentration, dynamic light scattering analysis showed evidence for protein aggregation mainly to tetramers and dimers.


Assuntos
Acebutolol/química , Varredura Diferencial de Calorimetria/métodos , Dicroísmo Circular/métodos , Fibrinogênio/química , Animais , Soluções Tampão , Bovinos , Físico-Química/métodos , Dimerização , Glicina/química , Concentração de Íons de Hidrogênio , Luz , Modelos Químicos , Dobramento de Proteína , Espalhamento de Radiação
12.
J AOAC Int ; 91(2): 322-31, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18476343

RESUMO

The stability of atenolol, acebutolol, and propranolol was investigated in sodium hydroxide solutions at concentrations of 0.1, 0.3, 0.5, and 1 M at 3 temperatures ranging from 37 to 95 degrees C. The degradation processes that occurred in drugs under investigation were described with kinetic parameters (k, t0.1, and t0.5) and energy of activation (Ea). It was found that the stability of the drugs increased toward lipophilic propranolol in the assumed experimental model. The rate constants k decreased, contrary to t0.1, t0.5, and Ea, which varied comparably to log P (partition coefficient), thus increasing from the most hydrophilic atenolol, through acebutolol of lower polarity, to the most lipophilic propranolol. The identification of degradation products was performed with the application of proton nuclear magnetic resonance spectrometry and thin-layer chromatography-densitometry and data from the literature.


Assuntos
Antagonistas Adrenérgicos beta/química , Acebutolol/química , Atenolol/química , Cromatografia em Camada Fina , Densitometria , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética , Propranolol/química
13.
J Chromatogr A ; 1138(1-2): 190-202, 2007 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-17097093

RESUMO

The use of chromatographic descriptors in QSAR was evaluated. Therefore, retentions were measured on an immobilized artificial membrane system, 2 micellar liquid chromatography systems and 17 orthogonal or disimilar reversed-phase liquid chromatographic systems. It was investigated whether it was possible to model gastro-intestinal absorption as a function of chromatographic retentions applying two linear and one non-linear multivariate modeling technique. In a second step it was evaluated if models built with theoretical descriptors could be improved by adding the measured retention factors to the data set of descriptive variables. It was seen that gastro-intestinal absorption could be modelled in function of chromatographic retention using the non-linear modeling technique multivariate adaptive regression splines (MARS). The best models were obtained using a combination of theoretical and chromatographic descriptors with MARS as modeling technique.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Absorção Intestinal , Preparações Farmacêuticas/metabolismo , Farmacocinética , Acebutolol/química , Acebutolol/farmacocinética , Algoritmos , Modelos Teóricos , Análise Multivariada , Preparações Farmacêuticas/química , Relação Quantitativa Estrutura-Atividade , Solventes , Verapamil/química , Verapamil/farmacocinética
14.
Pharm Dev Technol ; 11(4): 409-16, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17101511

RESUMO

The main objective of this research was to investigate the relationship between the polarity of atenolol, acebutolol, and propranolol described by logP and kinetic and thermodynamic parameters characterizing their degradation process in acidic solution. Hydrolysis was carried out in hydrochloric acid at molal concentrations of 0.1 mol/L, 0.5 mol/L, and 1 mol/L for 2 hr at 40 degrees C, 60 degrees C, and 90 degrees C. Chromatographic-densitometric method was used for the determination of drugs under investigation. The identification of degradation products was carried out by using 1H NMR. The degradation processes that occurred in drugs under investigation are described with kinetic parameters (k, t0.1, and t0.5) and energy of activation (Ea). It has been found that the stability of drugs increases toward lipophilic propranolol in the assumed experimental model. The rate constants k decrease, contrary to t0.1, t0.5, and Ea, which vary comparably to logP, thus increasing from the most hydrophilic atenolol, through acebutolol, of lower polarity, to the most lipophilic propranolol. This study demonstrated that the stability of chosen beta-adrenergic blocking agents increases with their lipophilicity.


Assuntos
Antagonistas Adrenérgicos beta/química , Estabilidade de Medicamentos , Acebutolol/química , Atenolol/química , Ácido Clorídrico , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Propranolol/química , Eletricidade Estática , Temperatura , Termodinâmica
15.
Chem Pharm Bull (Tokyo) ; 54(7): 1026-9, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16819224

RESUMO

A spectrofluorimetric method was described for the determination of drugs containing active methylene groups adjacent to carbonyl groups. The method was applied successfully to the determination of three life saving cardiovascular drugs, with narrow therapeutic indices: pentoxifylline (I), propafenone hydrochloride (II) and acebutolol hydrochloride (III), in laboratory-prepared mixtures, in commercial tablets and in plasma samples. The method involved the reaction of each of the tested drugs with N1-methyl nicotinamide chloride (NMNCl) in the presence of alkali, followed by addition of formic acid, where highly fluorescent reaction products were produced. The produced fluorescence were measured quantitatively at 472 nm (lambdaex 352 nm), 409 nm (lambdaex 310 nm) and 451 nm (lambdaex 266 nm) for (I), (II), and (III) respectively. The method was linear over concentration ranges of 10-1000 microg/ml , 0.2-12 microg/ml and 0.08-10 microg/ml in standard solutions for (I), (II), and (III) respectively. In spiked human plasma samples, calibration graphs were linear over concentration ranges of 20-1000 microg/ml, 0.2-15 microg/ml and 0.08-10 microg/ml for (I), (II), and (III) respectively. The method showed good accuracy, specificity and precision in both laboratory-prepared mixtures and spiked human plasma samples. The proposed method is simple, with low instrumentation requirements, suitable for quality control application, bioavailability and bioequivalency studies.


Assuntos
Corantes Fluorescentes/química , Metano/análogos & derivados , Niacinamida/análogos & derivados , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Acebutolol/análise , Acebutolol/química , Metano/química , Niacinamida/química , Pentoxifilina/análise , Pentoxifilina/química , Propafenona/análise , Propafenona/química , Espectrometria de Fluorescência
16.
Chirality ; 11(4): 267-71, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10224653

RESUMO

A stereoselective direct liquid chromatographic method for assay of the enantiomers of the beta-adrenergic blocker acebutolol (AC) and its active metabolite, diacetolol (DC), in human serum was developed. The assay is based on extraction with ethyl acetate and separation of enantiomers on an amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase (Chiralpak AD) column. The method was validated and proved useful for the determination of the enantiomers in serum samples of patients suffering from hypertension and chronically treated with racemic AC. The results were compared and found similar with an indirect assay based on derivatization of the enantiomers with (+)-(S)-1-(1-naphthyl)ethyl isocyanate (NEIC).


Assuntos
Acebutolol/análogos & derivados , Acebutolol/sangue , Anti-Hipertensivos/sangue , Acebutolol/química , Acebutolol/uso terapêutico , Anti-Hipertensivos/química , Anti-Hipertensivos/uso terapêutico , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Indicadores e Reagentes , Análise de Regressão , Estereoisomerismo
17.
J Chromatogr A ; 800(2): 161-9, 1998 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-9561760

RESUMO

Chromatographic retention factors (k') of a series of eight beta-adrenoceptor antagonist compounds (beta-adrenolytic drugs) were determined employing an immobilized artificial membrane column (IAM.PC.DD). The influence of mobile phase pH, ionic strength, and organic modifier composition was studied in order to examine column performance. After the IAM.PC.DD columns were exposed to approximately 7000 column volumes of a 0.01 M PBS mobile phase, five out of six columns tested showed significant peak broadening and decreased k' values indicative of premature column failure. The data suggested that the immobilized phospholipids stationary phase was removed by the 0.01 M PBS mobile phase. The beta-adrenolytic drug's log k'IAM values obtained with an IAM.PC.DD column were compared to an esterIAM.PC.MG column for predicting drug membrane interactions. For the linear regression analysis between log k'IAM and the logarithm of the n-octanol-water partition coefficients (rIAM.PC.DD = 0.8710 vs. rIAM.PC.MG = 0.9538), the C18 HPLC retention factors (rIAM.PC.DD = 0.8408 vs. rIAM.PC.MG = 0.9380), the liposome partition coefficients (rIAM.PC.DD = 0.8887 vs. rIAM.PC.MG = 0.9187), and various pharmacokinetic parameters, significantly better correlations were obtained with the esterIAM.PC.MG column than the IAM.PC.DD column.


Assuntos
Antagonistas Adrenérgicos beta/análise , Cromatografia Líquida de Alta Pressão/métodos , Membranas Artificiais , Fosfatidilcolinas/química , Acebutolol/análise , Acebutolol/química , Acetonitrilas/química , Antagonistas Adrenérgicos beta/química , Alprenolol/análise , Alprenolol/química , Compostos de Anilina/análise , Compostos de Anilina/química , Atenolol/análise , Atenolol/química , Concentração de Íons de Hidrogênio , Metoprolol/análise , Metoprolol/química , Modelos Químicos , Concentração Osmolar , Oxprenolol/análise , Oxprenolol/química , Pindolol/análise , Pindolol/química , Propranolol/análise , Propranolol/química , Reprodutibilidade dos Testes , Timolol/análise , Timolol/química
18.
J Chromatogr B Biomed Appl ; 683(2): 231-6, 1996 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-8891920

RESUMO

A method has been developed for the determination of total celiprolol (sum of enantiomers) or the enantiomers (R)-celiprolol and (S)-celiprolol in plasma by high-performance liquid chromatography with UV and fluorescence detection. After extraction from alkalinized plasma with methyl-tert.-butyl ether and back-extraction into 0.01 M HCl (for total celiprolol determination) or after evaporation of the organic phase and derivatisation with R(-)-1-(1-naphthyl)ethyl isocyanate (enantiomer determination), total celiprolol or its diastereomeric derivatives were chromatographed on a reversed-phase HPLC column with a mixture of acetonitrile and phosphate buffer pH 3.5 (+0.05% triethylamine). Acebutolol was used as internal standard. Linearity was obtained in the range of 5 to 2000 ng/ml for total and 2.5 to 500 ng/ml for enantiomer determination. Intra-day and inter-day variation was lower than 10%. The method can be applied for analysis of plasma samples obtained from patients treated with oral racemic celiprolol doses.


Assuntos
Antagonistas Adrenérgicos beta/sangue , Celiprolol/sangue , Cromatografia Líquida de Alta Pressão/métodos , Acebutolol/sangue , Acebutolol/química , Antagonistas Adrenérgicos beta/química , Celiprolol/química , Ritmo Circadiano , Humanos , Modelos Lineares , Padrões de Referência , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta , Estereoisomerismo
19.
Pharm Res ; 12(7): 1040-4, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7494799

RESUMO

PURPOSE: Poorly compressible crystals of acebutolol hydrochloride were agglomerated by the spherical crystallization technique with a two-solvent system to improve the compressibility for direct tabletting. The mechanism of improvements in static compression behaviors and tablettabilities of the spherically agglomerated crystals were investigated. METHODS: The improvement of static compression behaviors of the agglomerated crystals was determined by measuring the stress relaxations and elastic recoveries of compressed powder of original and agglomerated crystals. The improved tablettability of agglomerated crystals was evaluated by the pressure transmission ratio upon compression, the ejection pressure for releasing the tablet from the die and the tablet strength, i.e., tensile strength required for breaking. RESULTS: The higher relaxation pressure and the lower elastic recovery of the agglomerated crystals than of the original crystals were found. The pressure transmission ratio data showed that the friction pressures of the two crystals were similar during the compression period. The ejection pressure of the agglomerated crystals was lower than that of the original crystals. The tensile strength of the tablet of agglomerated crystals was greater than that of the original crystals. CONCLUSIONS: The compressibility and tablettability of the spherically agglomerated crystals prepared by the spherical crystallization technique were much improved due to their increased plastic property and reduced adhesive property compared to the original crystals.


Assuntos
Acebutolol/química , Química Farmacêutica/métodos , Comprimidos/química , Fenômenos Químicos , Físico-Química , Cristalização , Elasticidade , Pressão , Solventes/química , Resistência à Tração
20.
Pharm Res ; 12(3): 387-92, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7617526

RESUMO

A series of O-cyclopropane carboxylic acid ester prodrugs of various beta-blocking agents was synthesized. All prodrugs were hydrolyzed to give their parent compounds in aqueous phosphate buffer of pH 7.4 and in 80% human plasma. The half-lives in buffer solutions varied from 4 hours for the timolol prodrug to about 1 day for the prodrug of alprenolol. In human plasma the half-lives were shorter, ranging from 1 to 7 hours. The formation of the O-cyclopropane carboxylic acid ester derivatives significantly increased the lipophilicities of the beta-blockers as measured by the distribution coefficient between n-octanol and aqueous phosphate buffer of pH 7.4. To characterize the biomembrane permeability characteristics of the beta-blockers, transport properties across Caco-2 cell monolayers were investigated. An increase in lipophilicity resulted in a higher permeability of the prodrugs as compared to the parent compounds. Hence, acebutolol experienced an increment of a factor 17 on the apparent permeability coefficient, Papp, whereas Papp for the more lipophilic drug propranolol was increased by a factor of only 1.26. Some conversion of the prodrugs to their parent compounds was observed during the transport and appeared to be due to enzymatic intracellular metabolism.


Assuntos
Antagonistas Adrenérgicos beta/química , Sistemas de Liberação de Medicamentos , Ésteres/metabolismo , Acebutolol/química , Alprenolol/química , Células Cultivadas , Humanos , Hidrólise , Matemática , Permeabilidade , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...