RESUMO
Nordihydroguaiaretic acid (NDGA) occurs naturally in chaparral (Larrea tridentate Coville), a plant which commonly grows in the Southwest United States and has been used for medicinal purposes by Native Americans indigenous to that region. In addition to its traditional use as a tea, manufacturers of dietary supplements have marketed chaparral-containing products in a variety of formulations. Because of the hepatotoxicity of NDGA, and its occurrence in regulated products, we have developed a method for the determination of NDGA in dietary supplements and have tested this method in several dietary supplement formulations. Products were extracted with 80% methanol, filtered, and analyzed by high-performance liquid chromatography. NDGA was detected and determined with both a diode array detector and negative-ion electrospray. Fragmentation in the triple-quadrupole mass spectrometer was obtained by collisional activation of the [M-H](-) ion. Collisional activation produced sufficient fragmentation to provide unambiguous identification. Lack of a stable isotope labeled internal standard has led us to compare quantitations based on UV detection with quantitations based on tandem mass spectrometry (MS/MS). Presence of NDGA was confirmed in several dietary supplement products. Quantitative results from the 2 detection methods were comparable for most products. The limit of quantitation using MS/MS was lower and fewer interferences were observed, although UV detection provided better linearity.
Assuntos
Suplementos Nutricionais/análise , Análise de Alimentos/métodos , Larrea/química , Masoprocol/análise , Cromatografia Líquida de Alta Pressão/métodos , Suplementos Nutricionais/normas , Análise de Alimentos/normas , Indicadores e Reagentes , Masoprocol/normas , Padrões de Referência , Reprodutibilidade dos Testes , Soluções , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrofotometria Ultravioleta , Espectrometria de Massas em Tandem/métodosRESUMO
Nordihydroguaiaretic acid (NDGA) has been shown to inhibit both 5-lipoxygenase and ornithine decarboxylase and is active against several cancer cell lines and at least one mouse tumor model. Despite these findings, there have been no reports on the pharmacokinetics of NDGA. A reverse-phase high-performance liquid chromatography (HPLC) method was developed to detect NDGA in mouse plasma. The limit of detection of this method was 0.5 microg/ml. Administration of NDGA (50 mg/kg, i.v.) to mice resulted in a peak plasma concentration of 14.7 microg/ml. The terminal half-life of NDGA was 135.0 min with a clearance of 201.9 ml/min x kg.
