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1.
J Ethnopharmacol ; 171: 154-60, 2015 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-26055342

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Isoboldine is one of the major bioactive constituents in the total alkaloids from Radix Linderae (TARL) which could effectively alleviate inflammation and joints destruction in mouse collagen-induced arthritis. To better understand its pharmacological activities, we need to determine its pharmacokinetic and metabolic profiles. MATERIALS AND METHODS: In this study, a sensitive and simple UPLC-MS/MS method was developed and validated for determination of isoboldine in rat plasma. Isoboldine in plasma was recovered by liquid-liquid extraction using 1 mL of methyl tert-butyl ether. Chromatographic separation was performed on a C18 column at 45°C, with a gradient elution consisting of acetonitrile and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The detection was performed on an electrospray triple-quadrupole MS/MS by positive ion multiple-reaction monitoring mode. This newly developed method was successfully applied to a pharmacokinetic study after oral and intravenous dosing in rats. For metabolites identification, isoboldine was orally administered to rats and the metabolite in plasma, bile, urine and feces were characterized by the established UPLC-MS/MS method. RESULTS: Good linearity (r(2)>0.9956) was achieved in a concentration range of 4.8-2400 ng/mL with a lower limit of quantification of 4.8 ng/mL for isoboldine. The intra- and inter-day precisions of the assay were 1.7-5.1% and 2.2-4.4% relative standard deviation with an accuracy of 91.3-102.3%. A total of five phase II metabolites in rat plasma, bile, urine and feces were characterized by comparing retention time in UPLC, and by molecular mass and fragmentation pattern of the metabolites by mass spectrometry with those of isoboldine. CONCLUSION: isoboldine has extremely low oral bioavailability due to the strong first-pass effect by the rats, and glucuronidation and sulfonation were involved in metabolic pathways of isoboldine in rats. These results have paved the way for further clarifying therapeutic ingredients and provided new knowledge regarding pharmacokinetic features of this category of isoquinoline alkaloids.


Assuntos
Alcaloides/farmacocinética , Lindera , Raízes de Plantas , Alcaloides/sangue , Alcaloides/urina , Animais , Bile/química , Cromatografia Líquida de Alta Pressão , Fezes/química , Masculino , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
2.
Biomed Chromatogr ; 29(3): 459-64, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25065486

RESUMO

Boldine is a potential anti-inflammatory agent found in several different plants. Published bioanalytical methods using HPLC with ultraviolet and fluorescent detection lacked enough sensitivity and required tedious sample preparation procedures. Herein, we describe the development of a novel ultra-high performance LC with MS/MS for determination of boldine in plasma. Boldine in plasma was recovered by liquid-liquid extraction using 1 mL of methyl tert-butyl ether. Chromatographic separation was performed on a C18 column at 45°C, with a gradient elution consisting of acetonitrile and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The detection was performed on an electrospray triple-quadrupole MS/MS by positive ion multiple reaction monitoring mode. Good linearity (r(2) > 0.9926) was achieved in a concentration range of 2.555-2555 ng/mL with a lower limit of quantification of 2.555 ng/mL for boldine. The intra- and inter-day precisions of the assay were 1.2-6.0 and 1.8-7.4% relative standard deviation with an accuracy of -6.0-8.0% relative error. This newly developed method was successfully applied to a single low-dose pharmacokinetic study in rats and was demonstrated to be simpler and more sensitive than the published methods, allowing boldine quantification in reduced plasma volume.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Aporfinas/sangue , Aporfinas/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/análise , Aporfinas/administração & dosagem , Calibragem , Cromatografia Líquida de Alta Pressão/instrumentação , Estabilidade de Medicamentos , Injeções Intravenosas , Limite de Detecção , Masculino , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos
3.
J Pharm Biomed Anal ; 95: 158-63, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24682015

RESUMO

Mifepristone (RU486) is a chemical abortifacient used by hundreds of millions of women world-wide. It has recently been used in clinical trials for psychotic depression and cancer chemotherapy. Metapristone is the most predominant biological active metabolite of mifepristone, and being developed as a novel cancer metastasis chemopreventive agent based on its unique pharmacological properties. In this study, a novel rapid and sensitive method using UPLC/MS/MS was developed and validated for quantitative analysis of metapristone in plasma, which used less plasma volume and was demonstrated to be more simple and low-cost than the published methods. Metapristone in plasma was recovered by liquid-liquid extraction using 1 mL of ethyl acetate and chromatographic separation was carried on a C18 column at 35 °C, with a gradient mobile phase consisting of methanol and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The mass spectrometric detection was carried out using a triple-quadrupole system via positive electrospray ionization. Multiple reaction monitoring was used for quantitation of m/z transitions from 416.3 to 119.9 for metapristone and from 313.1 to 109 for levonorgestrel (internal standard). Good linearity (r²> 0.9926) was achieved over a concentration range from 7.1 to 2840 ng/mL with a lower limit of quantification of 7.1 ng/mL for metapristone. The intra- and inter-day variations of the assay were 2.4-10.0% relative standard deviation with an accuracy of -5.6 to 8.6% relative error. This newly developed method was successfully applied to a pharmacokinetic study that revealed, for the first time, that there was a significant difference in pharmacokinetic profile between genders.


Assuntos
Anticarcinógenos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Mifepristona/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Animais , Feminino , Limite de Detecção , Masculino , Mifepristona/sangue , Ratos , Ratos Sprague-Dawley
4.
J Sep Sci ; 37(3): 308-13, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24375943

RESUMO

Indole alkaloids are the main bioactive/toxic components in Gelsemium elegans Benth. To determine the distribution and contents of indole alkaloids in its different medicinal parts, a novel and rapid method using ultra-high performance LC (UPLC) with MS/MS has been established and validated with an optimized ultrasound/microwave-assisted extraction method. Four constituents, namely, humantenidine, humantenmine, gelsemine, and koumine, were simultaneously determined in 6 min. Chromatographic separation was achieved on an ultra-high performance LC BEH C18 column with a gradient mobile phase consisting of methanol and water (containing 0.1% formic acid both in methanol and water) at a flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole electrospray MS/MS by positive ion multiple-reaction monitoring mode. All the analytes showed good linearity (r ≥ 0.9934) within a concentration range from 0.1-25 µg/mL with a LOQ of 25-50 ng/mL. The overall intra- and intervariations of four components were <4.7% with an accuracy of 97.3-101.3%. The analysis results showed that there were remarkable differences in the distribution and contents of four chemical markers in the roots, stems, and leaves of G. elegans Benth. The findings can provide necessary and meaningful information for the rational utilization of its resources.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Gelsemium/química , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Plantas Medicinais/química , Espectrometria de Massas em Tandem/métodos , Ultrassom/métodos , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/toxicidade , Alcaloides Indólicos/toxicidade , Micro-Ondas , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Espectrometria de Massas por Ionização por Electrospray/métodos
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