Summary: | 碩士 === 中國文化大學 === 應用化學研究所 === 92 === Rutaecarpine, a main quinazolinocarboline alkaloid isolated from Evodia rutaecarpa, showed a variety pharmacological effects including antithrombotic and vasorelaxant effects. In previous studies, rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes. Four rutaecarpine oxidative metabolites (10-hydroxyrutaecarpine (1), 11-hydroxyrutaecarpine (2), 12-hydroxyrutaecarpine (3), 3-hydroxyrutaecarpine (4)) were characterized by comparison their 1H-NMR spectrum than that of authentic samples.
In order to establish a rapid and efficient analytical method to simultaneously identify four rutaecarpine metabolites, a liquid chromatography-eletrospray mass spectrometry (LC-MS) method was developed. A C18 column and a gradient elution were employed for the separation. Selective ion monitoring [M+H]+ (m/z = 304 for hydroxyrutaecarpines) was utilized for quantitative measurement and 4-methoxyrutaecarpine was used as internal standard. The standards calibration curves were linear (R2 > 0.9824) over the concentration range of 0.25-40.0 ppm. The relative standard deviations of hydroxyrutaecarpines ranged between 1.55~11.76 % (intraday); 2.09~9.80 % (interday). The limit of detection of the method is 0.05 ppm for 1, 0.05 ppm for 2, 0.1 ppm for 3, and 0.1 ppm for 4 per injection, respectively. When this LC/MS method was applied to four metabolites of rutaecarpine were 1.72 ppm for 1; 1.87 ppm for 2; 0.43 ppm for 3; 2.55 ppm for 4, respectively.
|