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1.
Acta Chim Slov ; 68(4): 811-820, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34918774

RESUMO

This study reports electrochemical treatment of different therapeutic classes of pharmaceuticals (caffeine, prazosin, enalapril, carbamazepine, nifedipine, levonorgestrel, and simvastatin) in a mixture. The electrochemical process was investigated using graphite-PVC anode at different applied voltages (3, 5, and 12 V), initial concentrations of studied pharmaceuticals in aqueous solution (5 and 10 mg/L), and concentrations of sodium chloride (1 and 2 g/L). The % removal of pharmaceuticals increased with the applied voltage, and was found higher than 98% after 50 min of electrolysis at 5 V. Energy consumption ranged between 0.760 and 3.300 Wh/mg using 12 V being the highest value compared to 3 and 5 V. The formation of chlorinated by-products from four selected pharmaceuticals, simvastatin (C11H13Cl3O5, and C10H12Cl4O3), prazosin (C13H12Cl3N5O3 and C10H11Cl4N2O2), carbamazepine and caffeine (C15H11N2O2Cl and C8H9N4O2Cl) was identified and elucidated using liquid chromatography-time of flight mass spectrometry (LC-TOF/MS).


Assuntos
Técnicas Eletroquímicas/métodos , Grafite/química , Preparações Farmacêuticas/química , Cloreto de Polivinila/química , Cafeína/análise , Cafeína/química , Cafeína/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Técnicas Eletroquímicas/instrumentação , Eletrodos , Oxirredução , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/isolamento & purificação , Prazosina/análise , Prazosina/química , Prazosina/isolamento & purificação , Sinvastatina/análise , Sinvastatina/química , Sinvastatina/isolamento & purificação , Cloreto de Sódio/química , Extração em Fase Sólida , Espectrometria de Massas por Ionização por Electrospray , Água/química
2.
J Pharm Biomed Anal ; 187: 113371, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32460215

RESUMO

This work was motivated by the demand of European Directorate for the Quality of Medicines and HealthCare (EDQM). A new liquid chromatographic (LC) method was developed for terazosin impurity profiling to replace the old European Pharmacopoeia (Ph. Eur.) method. This new method is published as part of the new Ph. Eur. monograph proposal of terazosin in Pharmeuropa issue 32.2. The aim of the method renewal was to cut the analysis time from 90 min (2 × 45 min) down to below 20 min. The Ph. Eur. monograph method is based on two different chromatographic separations to analyze the specified impurities of terazosin. The reason for the two methods is that two of the impurities are not sufficiently retained in reversed phase (RP) conditions, not even with 100% water as eluent. Therefore, next to RP, an ion-pair (IP) chromatographic method has to be applied to analyze those two impurities. With our new proposed method it was possible to appropriately increase the retention of the two critical compounds using alternative stationary phases (instead of a C18 phase which is suggested by the Ph. Eur. method). Applying a pentafluoro-phenyl (PFP) stationary phase, it was feasible to separate and adequately retain all the impurities. The detection wavelength was also changed compared to the Ph. Eur. method and is now appropriate for the detection and quantification of all impurities using perchloric acid in the mobile phase at low pH. Another goal of the present study was to develop a generic workflow and to evaluate the chromatographic resolution in a wide range of method variables and suggest some replacement columns for terazosin impurity profiling. Retention modeling was applied to study the chromatographic behavior of the compounds of interest and visualize resolution for the different columns, where a given criterion is fulfilled. A zone (set of chromatographic conditions) of a robust space could be then quickly identified by the overlay of the individual response surfaces (resolution maps). It was also demonstrated that two columns from different providers (Kinetex F5 and SpeedCore PFP) can be used as replacement columns, providing sufficient resolution at the same working point and a high degree of robustness.


Assuntos
Cromatografia Líquida/métodos , Cromatografia de Fase Reversa/métodos , Contaminação de Medicamentos , Prazosina/análogos & derivados , Europa (Continente) , Concentração de Íons de Hidrogênio , Farmacopeias como Assunto , Prazosina/análise , Prazosina/normas , Fatores de Tempo
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 236: 118349, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32305835

RESUMO

Counterfeit drugs have adverse effects on public health; chromatographic methods can be used but they are costly. In this study, we developed cost-effective and environmentally friendly methodology for the analysis of terazosin HCl (TZ) in the presence prazosin hydrochloride (PZ) using UV spectroscopy in conjunction with machine learning (ML) models. Variable selection algorithms were applied to select most informative spectral variables. Thirty-five ML models were assessed and their performances were compared. The models covered a wide range of prediction mechanisms, such as tree-based, linear, self-organizing maps, neural network, Gaussian process, boosting, bagging, Bayesian models, kernel methods, and quantile regression. The values of the root mean square error (RMSE), coefficient of determination (R2), and absolute mean error (MAE) were obtained for the evaluation of the developed models. According to the results of these performance indices, linear model showed the highest prediction capacity among all other models. RMSE, R2 and MAE values of (0.159, 0.997 and 0.131) and (0.196, 0.99 and 0.161) were obtained for train and test datasets, respectively. The predictive models in this study can be useful for the researchers who are interested to work on the determination of active ingredients in pharmaceutical dosage forms in the presence of interference using UV spectroscopy; therefore, it was used to determine TZ without interference of PZ.


Assuntos
Medicamentos Falsificados/análise , Aprendizado de Máquina , Prazosina/análogos & derivados , Prazosina/análise , Espectrofotometria Ultravioleta/métodos , Algoritmos , Teorema de Bayes , Química Verde , Redes Neurais de Computação , Espectrofotometria Ultravioleta/estatística & dados numéricos , Comprimidos/análise
4.
Mikrochim Acta ; 186(12): 801, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741056

RESUMO

A surface-enhanced Raman scattering (SERS) method is described for the determination of prazosin (PRH) and losartan (LOS). Silver nanoparticles modified with ß-cyclodextrin (CD-S-Ag NPs) were prepared and serve as a sensitive SERS substrate. ß-CD is both a reductant for silver ions and a host molecule that binds the analytes which leads to strong SERS enhancement. The method has distinct features: (a) The linear response extends from 0.1 to 60 µM for PRH, and from 1.0 to 100 µM for LOS; (b) the respective limits of detection are as low as 15 nM and 0.92 µM; and (c) the specific SERS bands of PRH and LOS are located at 703 and 1298 cm-1 respectively. The method was successfully applied to the determination of PRH and LOS illegally added to healthcare products. The recovery of PRH and LOS from spiked samples ranges between 91.3 and 109.3%, and from 87.4 to 105.2%, respectively, both with relative standard deviation of <5%. Graphical abstractSchematic representation of a SERS method involving ß-CD-S-Ag nanoparticles for determination of prazosin and losartan via formation of an inclusion complex.


Assuntos
Anti-Hipertensivos/análise , Losartan/análise , Nanopartículas Metálicas/química , Prazosina/análise , Prata/química , beta-Ciclodextrinas/química , Tamanho da Partícula , Análise Espectral Raman , Propriedades de Superfície
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 195: 215-222, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29414581

RESUMO

A new, selective and sensitive spectrofluorimetric method was designed for the quantitation of doxazosin (DOX), terazosin (TER) and alfuzosin (ALF) in their dosage forms and human plasma. The method adopts efficient derivatization of the studied drugs with ortho-phthalaldehyde (OPA), in the presence of 2-mercaptoethanol in borate buffer (pH9.7) to generate a highly fluorescent isoindole derivatives, which can strongly enhance the fluorescence intensities of the studied drugs, allowing their sensitive determination at 430nm after excitation at 337nm. The fluorescence-concentration plots were rectilinear over the ranges (10.0-400.0) ng/mL. Detection and quantification limits were found to be (0.52-3.88) and (1.59-11.76) ng/mL, respectively. The proposed method was validated according to ICH guidelines, and successfully applied for the determination of pharmaceutical preparations of the studied drugs. Moreover, the high sensitivity of the proposed method permits its successful application to the analysis of the studied drugs in spiked human plasma with % recovery (96.12±1.34-100.66±0.57, n=3). A proposal for the reaction mechanism was presented.


Assuntos
Doxazossina/análise , Plasma/metabolismo , Prazosina/análogos & derivados , Quinazolinas/análise , Espectrometria de Fluorescência/métodos , o-Ftalaldeído/química , Doxazossina/química , Fluorescência , Humanos , Limite de Detecção , Plasma/química , Prazosina/análise , Prazosina/química , Quinazolinas/química
6.
Braz. J. Pharm. Sci. (Online) ; 54(4): e17228, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001591

RESUMO

In the current work, a sustained drug delivery system of flutamide (FLT) was developed using Poly(D,L-lactide-co-glycolide) (PLGA) decorated bypoly(ethylene glycol) (PEG) grafted prazosin (PLGA-PEG-Praz) as a targeting moiety. In a multi-step reaction, PLGA was linked to PEG and prazosin. The structure of the synthesized polymers was confirmed by FTIR and 1H-NMR. Flutamide-loaded nanoparticles were prepared by quasi-emulsion solvent diffusion technique. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency, and release properties. Also, the physicochemical properties of the nanoparticles were analyzed using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry, and Powder X-Ray Diffractometry (XRD). The particle size of nanoparticles was ranged between 191 and 249 nm. Loading efficiency of nanoparticles was about 43%-69%. Results showed a steady release rate for nanoparticles compared to that of a pure drug powder. SEM characterization confirmed that particles were in nanosize range. DSC and XRPD results verified a decrease in drug crystallinity in the prepared formulations. In conclusion, the results of this study showed that PLGA-PEG-Praz nanoparticles could be a good choice to improve the physicochemical properties of the drug and these formulations can increase Flutamide efficacy.


Assuntos
Prazosina/análise , Nanopartículas , Flutamida/uso terapêutico , Neoplasias da Próstata/fisiopatologia , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentação
7.
Mater Sci Eng C Mater Biol Appl ; 75: 368-374, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28415474

RESUMO

In this approach, palladium nanoparticle film was simply fabricated on the surface of carbon paste electrode by electrochemical deposition method. The film was characterized using scanning electron microscopy, electrochemical impedance spectroscopy and cyclic voltammetry. The prepared electrode exhibited an excellent electrocatalytic activity toward detection of trace amounts of terazosin, which is an antihypertensive drug. Under the optimum experimental conditions, a linear range of 1.0×10-8-1.0×10-3molL-1 with a detection limit of 1.9×10-9molL-1 was obtained for determination of terazosin using differential pulse voltammetry as a sensitive method. The efficiency of palladium nanoparticle film on the surface of carbon paste electrode successfully proved for determination of terazosin in pharmaceutical sample and human serum sample with promising recovery results. The effect of some foreign species has been studied.


Assuntos
Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Paládio/química , Prazosina/análogos & derivados , Humanos , Prazosina/análise , Prazosina/farmacocinética
8.
Luminescence ; 32(6): 1066-1071, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28303653

RESUMO

A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm. Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over a concentration range of 70-900 ng ml-1 , with quantitation limits 27.1 and 32.2 ng ml-1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied to the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/análise , Prazosina/análogos & derivados , Quinazolinas/análise , Espectrometria de Fluorescência/métodos , Antagonistas de Receptores Adrenérgicos alfa 1/sangue , Formas de Dosagem , Humanos , Plasma/química , Prazosina/análise , Prazosina/sangue , Quinazolinas/sangue
9.
J Pharm Biomed Anal ; 135: 8-15, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-27987393

RESUMO

An older method for terazosin was reworked in order to reduce the analysis time from 90min (2×45min) to below 5min. The method in European Pharmacopoeia (Ph.Eur.) investigates the specified impurities separately. The reason of the different methods is that the retention of two impurities is not adequate in reversed phase, not even with 100% water. Therefore ion-pair-chromatography has to be applied and since that two impurities absorb at low UV-wavelength they had to be analyzed by different method than the other specified impurities. In our new method we could improve the retention with pH elevation using a new type of stationary phases available for high pH applications. Also a detection wavelength could be selected that is appropriate for the detection and quantification of all impurities. The method development is the bottleneck of liquid chromatography even today, when more and more fast chromatographic systems are used. Expert knowledge with intelligent programs is available to reduce the time of method development and offer extra information about the robustness of the separation. Design of Experiments (DoE) for simultaneous optimization of gradient time (tG), temperature (T) and ternary eluent composition (tC) requires 12 experiments. A good alternative way to identify a certain peak in different chromatograms is the molecular mass of the compound, due to its high specificity. Liquid Chromatography-Mass Spectrometry (LC-MS) is now a routine technique and increasingly available in laboratories. In our experiment for the resolution- and retention modeling the DryLab4 method development software (Version 4.2) was used. In recent versions of the software the use of (m/z)-MS-data is possible along the UV-peak-area-tracking technology. The modelled and measured chromatograms showed excellent correlations. The average retention time deviations were ca. 0.5s and there was no difference between the predicted and measured Rs,crit -values.


Assuntos
Modelos Moleculares , Farmacopeias como Assunto , Prazosina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Europa (Continente) , Espectrometria de Massas/métodos , Espectrometria de Massas/normas , Farmacopeias como Assunto/normas , Prazosina/análise , Prazosina/química , Espectrometria de Massas em Tandem/normas
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 147: 178-84, 2015 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-25840026

RESUMO

Herein, a Rayleigh light-scattering (RLS) detection method combined with high performance liquid chromatograph (HPLC) without any post-column probe was developed for the separation and determination of three α1-adrenoceptor antagonists. The quantitative analysis is benefiting from RLS signal enhancement upon addition of methanol which induced molecular aggregation to form an hydrophobic interface between aggregates and water that produce a sort of superficial enhanced scattering effect. A good chromatographic separation among the compounds was achieved using a Gemini 5u C18 reversed phase column (250 mm × 4.6 mm; 4 µm) with a mobile phase consisting of methanol and ammonium acetate-formic acid buffer solution (25 mM; pH=3.0) at the flow rate of 0.7 mL min(-1). The RLS signal was monitored at λex=λem=354 nm. A limit of detection (LOD) of 0.065-0.70 µg L(-1) was reached and a linear range was found between peak height and concentration in the range of 0.75-15 µg L(-1) for doxazosin mesylate (DOX), 0.075-3.0 µg L(-1) for prazosin hydrochloride (PRH), and 0.25-5 µg L(-1) for terazosin hydrochloride (TEH), with linear regression coefficients all above 0.999. Recoveries from spiked urine samples were 88.4-99.0% which is within acceptable limits. The proposed method is convenient, reliable and sensitive which has been used successfully in human urine samples.


Assuntos
Antagonistas Adrenérgicos alfa/urina , Cromatografia Líquida de Alta Pressão/métodos , Doxazossina/urina , Difusão Dinâmica da Luz/métodos , Prazosina/análogos & derivados , Prazosina/urina , Antagonistas Adrenérgicos alfa/análise , Dimerização , Doxazossina/análise , Humanos , Ligação de Hidrogênio , Limite de Detecção , Modelos Moleculares , Prazosina/análise
11.
Neurogastroenterol Motil ; 26(8): 1095-103, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24906134

RESUMO

BACKGROUND: The role of α-adrenoceptors in promoting continence through modulation of sphincter tone has focused primarily on the effects of α1 -adrenoceptors. We have used three clinically available agents, which are selective for α2 -adrenoceptors, to investigate their role in contractile and neurogenic responses on the internal anal sphincter (IAS). METHODS: IAS strips, which had spontaneously generated tone, were used to investigate the contractile effect of lofexidine, brimonidine, and dexmedetomidine on muscle tone in the presence or absence of subtype selective antagonists. The effect of brimonidine on the magnitude and time course of neurogenic responses generated by electrical field stimulation (EFS) was also examined. The affinity of test compounds at α1 - and α2 -adrenoceptors was established by competition binding with [3H]-prazosin and [3H]-RX821002. KEY RESULTS: All agonists caused concentration-dependent contraction of the IAS and lofexidine demonstrated an enantiomeric difference in potency with a 10-fold difference between the (-) and (+) isomers. Responses to lofexidine and dexmedetomidine were inhibited in the presence of the α1 -adrenoceptor selective antagonist prazosin, but not in the presence of RX811059 (α2 -adrenoceptor selective antagonist); brimonidine responses were inhibited by RX811059 and, to a lesser extent, by prazosin. Brimonidine affected both magnitude and duration of neurogenic responses, which was reversed in the presence of RX811059. CONCLUSIONS & INFERENCES: We conclude that α2 -adrenoceptors can mediate contraction of IAS, although this effect is most evident with efficacious imidazoline agonists rather than the most selective ligand. In addition, this receptor subtype can directly inhibit noradrenergic contractile responses to EFS and, indirectly, enhance nitrergic relaxatory responses.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Canal Anal/efeitos dos fármacos , Canal Anal/fisiologia , Receptores Adrenérgicos alfa/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/metabolismo , Animais , Tartarato de Brimonidina , Clonidina/análogos & derivados , Clonidina/metabolismo , Clonidina/farmacologia , Dexmedetomidina/metabolismo , Dexmedetomidina/farmacologia , Contração Muscular/efeitos dos fármacos , Prazosina/análise , Prazosina/farmacologia , Quinoxalinas/metabolismo , Quinoxalinas/farmacologia , Ensaio Radioligante , Ovinos , Técnicas de Cultura de Tecidos
12.
ACS Comb Sci ; 16(4): 155-9, 2014 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-24628108

RESUMO

The performance of α1-adrenoceptor antagonists in living cells was assessed using quantum dots conjugated to a derivative of the α1-adrenoceptor antagonist prazosin. The optimum receptor binding condition and apparent Kd of prazosin-conjugated quantum dots was first determined, followed by application of these structures to drug screening. Total internal reflection fluorescence microscopy and flow cytometry were used to visually and quantitatively measure the affinity of five candidate drugs. The observed affinity order and the affinity coefficient Ki were consistent with previously reported values. These results suggest that this method is suitable for specific drug screening in living cells and is able to realize the displacement assay over the large ranges of dissociation constants.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/análise , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Pontos Quânticos , Sobrevivência Celular , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Prazosina/análise , Prazosina/farmacologia , Receptores Adrenérgicos alfa 1/metabolismo , Relação Estrutura-Atividade
13.
J Fluoresc ; 23(6): 1301-11, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23873207

RESUMO

A rapid, sensitive and selective flow injection analysis (FIA) method was developed for the determination of some selective α1-blockers including; terazosin (TER), doxazosin (DOX), prazosin (PRZ), and alfuzosin (ALF). The method was based on enhancement of the native fluorescence of the studied drugs in the presence of sodium dodecyl sulfate (SDS). The method was optimized for the buffer type, concentration and pH, surfactant type and concentration, flow rate and detection wavelengths in order to achieve the maximum sensitivity. The results showed that the best sensitivity was obtained by using SDS (10 mM) in phosphate buffer (20 mM, pH = 3), flow rate was 0.5 ml/min and the detector was set at λex = 250 and λem = 389. Under these optimum conditions there was a linear relationship between the concentration and the fluorescence intensity in the range from 5-400 ng ml(-) with correlation coefficient of more than 0.998. The detection and quantitation limits for the studied drugs by the proposed method were 3.2-11.9 ng ml(-1) and 10.8-39.7 ng ml(-1), respectively. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for intended applications. Moreover, the binding constants for α1-blockers -SDS system were determined using the adduct model. The proposed method has been applied successfully for the analysis of the pure forms for studied drugs and also their pharmaceutical formulations and the results were compared with official methods.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/análise , Análise de Injeção de Fluxo , Fluorescência , Internet , Doxazossina/análise , Micelas , Prazosina/análogos & derivados , Prazosina/análise , Quinazolinas/análise , Espectrometria de Fluorescência , Fatores de Tempo
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 878(26): 2415-20, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20732837

RESUMO

An enantioselective and sensitive method was developed and validated for determination of doxazosin enantiomers in human plasma by liquid chromatography-tandem mass spectrometry. The enantiomers of doxazosin were extracted from plasma using ethyl ether/dichloromethane (3/2, v/v) under alkaline conditions. Baseline chiral separation was obtained within 9 min on an ovomucoid column using an isocratic mobile phase of methanol/5mM ammonium acetate/formic acid (20/80/0.016, v/v/v) at a flow rate of 0.60 mL/min. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode, using the transitions of m/z 452-->344 for doxazosin enantiomers, and m/z 384-->247 for prazosin (internal standard). The method was linear in the concentration range of 0.100-50.0 ng/mL for each enantiomer using 200 microL of plasma. The lower limit of quantification (LLOQ) for each enantiomer was 0.100 ng/mL. The intra- and inter-assay precision was 5.0-11.1% and 5.7-7.6% for R-(-)-doxazosin and S-(+)-doxazosin, respectively. The accuracy was 97.4-99.5% for R-(-)-doxazosin and 96.8-102.8% for S-(+)-doxazosin. No chiral inversion was observed during the plasma storage, preparation and analysis. The method proved adequate for enantioselective pharmacokinetic studies of doxazosin after oral administration of therapeutic doses of racemic doxazosin.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/sangue , Cromatografia Líquida/métodos , Doxazossina/sangue , Ovomucina/química , Espectrometria de Massas em Tandem/métodos , Antagonistas de Receptores Adrenérgicos alfa 1/química , Antagonistas de Receptores Adrenérgicos alfa 1/farmacocinética , Doxazossina/química , Doxazossina/farmacocinética , Estabilidade de Medicamentos , Humanos , Análise dos Mínimos Quadrados , Prazosina/análise , Prazosina/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estereoisomerismo
15.
Anal Chim Acta ; 650(1): 143-9, 2009 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-19720185

RESUMO

Two second-order calibration methods based on the parallel factor analysis (PARAFAC) and the alternating penalty trilinear decomposition (APTLD) method, have been utilized for the direct determination of terazosin hydrochloride (THD) in human plasma samples, coupled with the excitation-emission matrix fluorescence spectroscopy. Meanwhile, the two algorithms combing with the standard addition procedures have been applied for the determination of terazosin hydrochloride in tablets and the results were validated by the high-performance liquid chromatography with fluorescence detection. These second-order calibrations all adequately exploited the second-order advantages. For human plasma samples, the average recoveries by the PARAFAC and APTLD algorithms with the factor number of 2 (N=2) were 100.4+/-2.7% and 99.2+/-2.4%, respectively. The accuracy of two algorithms was also evaluated through elliptical joint confidence region (EJCR) tests and t-test. It was found that both algorithms could give accurate results, and only the performance of APTLD was slightly better than that of PARAFAC. Figures of merit, such as sensitivity (SEN), selectivity (SEL) and limit of detection (LOD) were also calculated to compare the performances of the two strategies. For tablets, the average concentrations of THD in tablet were 63.5 and 63.2 ng mL(-1) by using the PARAFAC and APTLD algorithms, respectively. The accuracy was evaluated by t-test and both algorithms could give accurate results, too.


Assuntos
Antagonistas Adrenérgicos alfa/análise , Prazosina/análogos & derivados , Espectrometria de Fluorescência/métodos , Antagonistas Adrenérgicos alfa/sangue , Algoritmos , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Análise Fatorial , Corantes Fluorescentes/química , Humanos , Prazosina/análise , Prazosina/sangue , Espectrometria de Fluorescência/normas , Comprimidos
16.
Rapid Commun Mass Spectrom ; 22(19): 3015-26, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18763271

RESUMO

Metabolite identification studies remain an integral part of pre-clinical and clinical drug development programs. Analysis of biological matrices, such as plasma, urine, feces and bile, pose challenges due to the large amounts of endogenous components that can mask a drug and its metabolites. Although direct infusion nanoelectrospray using capillaries has been used routinely for proteomic studies, metabolite identification has traditionally employed liquid chromatographic (LC) separation prior to analysis. A method is described here for rapid metabolite profiling in biological fluids that involves initial sample clean-up using pipette tips packed with reversed-phase material (i.e. ZipTips) to remove matrix components followed by direct infusion nanoelectrospray on an LTQ/Orbitrap mass spectrometer using a protonated polydimethylcyclosiloxane cluster ion for internal calibration. We re-examined samples collected from a prazosin metabolism study in the rat. Results are presented that demonstrate that sub parts-per-million accuracies can be achieved on molecular ions, facilitating identification of metabolites, and on product ions, facilitating structural assignments. The data also show that the high-resolution measurements (R = 100,000 at m/z 400) enable metabolites of interest to be resolved from endogenous components. The extended analysis times available with nanospray enables signal averaging for 1 min or more that is valuable when metabolites are present in low concentrations as encountered here in plasma and brain. Using this approach, the metabolic fate of a drug can be quickly obtained. A limitation of this approach is that metabolites that are structural isomers cannot be distinguished, although such information can be collected by LC/MS during follow-on experiments.


Assuntos
Líquidos Corporais/metabolismo , Microquímica/métodos , Nanotecnologia/métodos , Prazosina/farmacocinética , Manejo de Espécimes/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Anti-Hipertensivos/análise , Anti-Hipertensivos/farmacocinética , Líquidos Corporais/química , Masculino , Microquímica/instrumentação , Nanotecnologia/instrumentação , Prazosina/análise , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/instrumentação
17.
Rapid Commun Mass Spectrom ; 20(2): 284-90, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16345125

RESUMO

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry is generally considered to be a surface analysis technique. In this report, the profiling depth of imaging mass spectrometry was examined. MALDI matrix solution was found to be able to gain access to the tissue interior and extract analyte molecules to the tissue surface. As a consequence, prazosin, a small molecule pharmaceutical compound, located as deep as 40 microm away from the surface was readily detected after matrix application. Likewise, cytochrome c, a 12 kDa protein, was also detectable from the tissue interior. Moreover, for prazosin, not only the extent of matrix effect, but also the extraction efficiency of the matrix solvent appeared to be dependent on the type of tissue. These results indicated that experimental conditions that decrease the matrix solvent evaporation during matrix application may increase analyte extraction efficiency and hence sensitivity of the analysis. Furthermore, thin sections should be used to avoid differential extraction efficiency of matrix solvent in different tissues for whole-body analysis.


Assuntos
Encéfalo/metabolismo , Citocromos c/metabolismo , Fígado/metabolismo , Microscopia Confocal/métodos , Prazosina/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tomografia/métodos , Animais , Técnicas In Vitro , Fígado/citologia , Camundongos , Prazosina/análise , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual
18.
Mol Imaging ; 4(1): 40-52, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15967125

RESUMO

Fluorescent ligands provide the means of studying receptors in whole tissues using confocal laser scanning microscopy and have advantages over antibody- or non-fluorescence-based method. Confocal microscopy provides large volumes of images to be measured. Histogram analysis of 3-D image volumes is proposed as a method of graphically displaying large amounts of volumetric image data to be quickly analyzed and compared. The fluorescent ligand BODIFY FL-prazosin (QAPB) was used in mouse aorta. Histogram analysis reports the amount of ligand-receptor binding under different conditions and the technique is sensitive enough to detect changes in receptor availability after antagonist incubation or generic manipulations. QAPB binding was concentration dependent, causing concentration-related rightward shifts in histogram. In the presence of 10 microM phenoxybenzamine (blocking agent), the QAPB (50 nM) histogram overlaps the autofluorescence curve. The histogram obtained for the 1D knockout aorta lay to the left of that control and 1B knockout aorta, indicating a reduction in 1D receptors. We have shown, for the first time, that it is possible to graphically display binding of a fluorescent drug to a biological tissue. Although our application is specific to adrenergic receptors, the general method could be applied to any volumetric, fluorescence-image-based assay.


Assuntos
Corantes Fluorescentes/análise , Microscopia Confocal/métodos , Prazosina/metabolismo , Antagonistas Adrenérgicos alfa/análise , Antagonistas Adrenérgicos alfa/metabolismo , Animais , Anticorpos/farmacologia , Aorta/efeitos dos fármacos , Aorta/metabolismo , Compostos de Boro/análise , Compostos de Boro/metabolismo , Relação Dose-Resposta a Droga , Feminino , Corantes Fluorescentes/metabolismo , Imageamento Tridimensional/métodos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Knockout , Fenoxibenzamina/farmacologia , Prazosina/análise , Prazosina/química , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/imunologia , Receptores Adrenérgicos alfa 1/metabolismo
19.
J Pharm Biomed Anal ; 34(1): 19-26, 2004 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-14738915

RESUMO

The present paper describes development of stability-indicating high-performance liquid chromatographic (HPLC) assay methods for three alpha-adrenergic-blocker drug substances, namely, prazosin, terazosin and doxazosin, in the presence of degradation products generated from forced decomposition studies. Resolution of drugs from degradation products was obtained using a reversed-phase C-18 column using water/acetonitrile/methanol/glacial acetic acid/diethylamine (25:35:40:1:0.017) as mobile phase for prazosin and terazosin and acetonitrile/water/glacial acetic acid/diethylamine (65:35:1:0.02) for doxazosin. The detection was done at 254 nm. The methods were validated with respect to linearity, precision, accuracy, specificity and robustness.


Assuntos
Doxazossina/análise , Prazosina/análogos & derivados , Prazosina/análise , Cromatografia Líquida de Alta Pressão/métodos , Doxazossina/química , Prazosina/química , Reprodutibilidade dos Testes , Estresse Mecânico
20.
J Pharm Biomed Anal ; 34(1): 115-21, 2004 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-14738925

RESUMO

This report introduces a fully automated flow system for drug-dissolution studies based on the coupling of the sequential injection analysis (SIA) technique with a conventional dissolution apparatus. The methodology described was used for monitoring of dissolution profiles of prazosin hydrochloride (PRH) in pharmaceutical formulation. The very sensitive fluorimetric detection of PRH was performed at lambda(ex)=244 nm (lambda(em)>or=389 nm). Under the optimal conditions, the calibration curve was linear over the range 0.02-2.43 mg x l(-1) of PRH with R.S.D. 1.89, 1.23, and 1.80% (n=10) when determining 0.02, 1.22, and 2.43 mg x l(-1) of PRH in standard solutions, respectively. Equation of the calibration curve was calculated giving the following values: F=4.108 c-3.9 (n=6), r=0.9996. Detection limit was calculated 0.007 mg x l(-1) of PRH. The dissolution test of Deprazolin tablets was programmed for 60 min, with a continuous sampling rate of 70 h(-1) under conditions required by USP 26. Results obtained by SIA technique compared well with HPLC standard method.


Assuntos
Prazosina/análise , Prazosina/normas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Análise de Injeção de Fluxo/métodos , Análise de Injeção de Fluxo/normas , Prazosina/química , Controle de Qualidade , Solubilidade/efeitos dos fármacos , Espectrofotometria Ultravioleta/métodos , Espectrofotometria Ultravioleta/normas , Comprimidos
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