Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Chromatogr B Biomed Sci Appl ; 754(2): 527-31, 2001 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-11339297

RESUMO

This study describes an expedient assay for the analysis of the asthma medication, montelukast sodium (Singulair, MK-0476), in human plasma samples. After a simple extraction of the plasma, the drug and internal standard, quinine bisulfate, were measured by HPLC. The chromatographic system consisted of a single pump, a refrigerated autosampler, a C8 4-microm particle size radial compression cartridge at 40 degrees C and a fluorescence detector with the excitation and emission wavelengths set at 350 and 400 nm, respectively. The mobile phase which was delivered at 1.0 ml/min, was prepared by adding 200 ml of 0.025 M sodium acetate, pH adjusted to 4.0 with acetic acid, to 800 ml of acetonitrile, with 50 microl triethylamine. With a run time of only 10 min per sample, this assay had an overall recovery of >97% with a detection limit of 1 ng/ml. The inter- and intra-run relative standard deviations at 0.05, 0.2 and 1.0 microg/ml were all <9.2%, while the analytical recovery at the same concentrations were within 7.7% of the amount added.


Assuntos
Acetatos/sangue , Antiasmáticos/sangue , Asma/sangue , Cromatografia Líquida de Alta Pressão/métodos , Quinolinas/sangue , Ciclopropanos , Fluorescência , Humanos , Luz , Controle de Qualidade , Padrões de Referência , Sulfetos
2.
J Clin Pharmacol ; 39(11): 1136-42, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10579143

RESUMO

This study was undertaken to examine the pharmacokinetics of both enantiomers of AG--that is, (R-AG) and (S-AG) and respective acetyl metabolites, R-AcAG and S-AcAG--in breast cancer patients. Six patients received a single dose (500 mg) of the racemic drug, and serial plasma samples and urine were collected over a 48-hour period. R-AG, S-AG, R-AcAG, and S-AcAg were measured simultaneously by high-performance liquid chromatography using two serial chiral separation columns with ultraviolet detection. The plasma concentrations of R-AG were about 1.5 times higher than those of S-AG, and the data for both enantiomers exhibited the characteristics of the one-compartment open model. There were no significant differences between R- and S-AG in ka, tmax, V/F, and t1/2. The formation of R- and S-AcAG was rapid, and no correlation was found between the t1/2 values of the AG enantiomers with that of their acetylated metabolites. Overall, 41% of the dose was excreted in urine as AG (15% R-AG and 26% S-AG) and 5.1% as AcAG (2.9% R-AcAG and 2.2% S-AcAG). Renal clearance of S-AG was significantly greater (i.e., 2.3-fold) than that of R-AG and appears to be most likely the cause for the other pharmacokinetic differences observed. Both enantiomers had low renal extraction ratios, suggesting extensive tubular reabsorption of the compounds. However, based on the data obtained, it was concluded that the main factor contributing to the therapeutic effectiveness of racemic AG is the large potency difference between the R- and S- forms (R > S). The pharmacokinetic differences between R-AG and S-AG appear to contribute only marginally to the activity of this drug as an aromatase inhibitor.


Assuntos
Aminoglutetimida/farmacocinética , Antineoplásicos Hormonais/farmacocinética , Neoplasias da Mama/metabolismo , Adulto , Idoso , Aminoglutetimida/sangue , Aminoglutetimida/urina , Antineoplásicos Hormonais/sangue , Antineoplásicos Hormonais/urina , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pós-Menopausa , Estereoisomerismo , Fatores de Tempo
3.
Ther Drug Monit ; 17(5): 538-43, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8585120

RESUMO

An accurate and specific liquid chromatographic method for the separation and analysis of the R(+) and S(-) enantiomers of both aminoglutethimide (AG) and its acetylated metabolite (AcAG) in plasma, saliva, and urine is described. The separation was achieved by use of two serial Chiralcel OD columns [cellulose tris(3,5-dimethylphenyl carbamate)] with a mixture of hexane/isopropanol/methanol (65:17.5:17.5, per volume) as a mobile phase. The flow rate was 0.7 ml/min, and the compounds were detected in the effluent spectrophotometrically at 245 nm. The plasma, saliva, or urine sample (300 microliters) was extracted with dichloromethane after the addition of an equal volume of acetate buffer (pH 5.6) to the sample. The extraction recovery of the R(+) and S(-) enantiomers of AG and AcAG from plasma, saliva, and urine at different concentrations under these conditions was > 80.9%. No interference from any endogenous substance or concomitantly used drug was observed. The ratio of the peak area of R(+) and S(-) enantiomers of both AG and AcAG/internal standard was linearly (r > or = 0.995) related to concentration in the range 0.83-40.0 micrograms/ml, and the coefficient of variation (CV) at different concentrations was consistently < or = 13%. We are presently employing this method to study the pharmacokinetics of each of these enantiomers in breast cancer patients.


Assuntos
Aminoglutetimida/análogos & derivados , Aminoglutetimida/análise , Antineoplásicos Hormonais/análise , 1-Propanol/química , Acetilação , Aminoglutetimida/sangue , Aminoglutetimida/metabolismo , Aminoglutetimida/uso terapêutico , Aminoglutetimida/urina , Antineoplásicos Hormonais/sangue , Antineoplásicos Hormonais/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/urina , Neoplasias da Mama/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Feminino , Hexanos/química , Humanos , Concentração de Íons de Hidrogênio , Metanol/química , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Padrões de Referência , Reprodutibilidade dos Testes , Saliva/química , Saliva/metabolismo , Estereoisomerismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...