利用高效液相層析儀定量Xanthonolol在大白鼠體內血中濃度及其藥物動力學分析   全文下載

Determination of Xanthonolol by High Performance Liquid Chromatography for Pharmacokinetic Studies in Rats

本研究建立一個快速、簡便的高效液相層析方法以定量xanthonolol在大白鼠體內之血中濃度。血液檢品的處理採液相萃取方法，以phenazine為內部標準品，利用碳十八逆相層析管以固定比例之移動相進行分析，移動相之組成包括含有0.05%三乙胺之65% McIlvaine緩衝溶液以磷酸調整酸驗值為6.4，18% 氰甲烷及17% 甲醇，在紫外光源波長235 nm下進行檢測，最低可定量濃度為50ng／mL，並以此條件進行大白鼠體內藥物動力學之分析，由xanthonolol血中濃度對應時間之數據顯示，以具一階次排除過程之二室式開放模式為最適化之動力學模式。Xanthonolol分別以5、10及15 mg／kg三種不同之劑量經靜脈注射給予後，其擬似分佈體積、排除半衰期及出清率等參數在不同劑量下均無顯著性差異，且其血中濃度經時間曲線下面積在三種不同劑量下隨劑量上升呈比例增加，顯示xanthonolol在給予之劑量下於大白鼠體內呈現線性藥物動力學模式。

A rapid and simple HPLC method was developed for the determination of xanthonolol concentration in plasma. The sample preparation utilized liquid-liquid extraction before injection into the HPLC system. Phenazine was used as the internal standard. Separation was obtained using a reversed-phase column under isocratic conditions. The mobile phase consisted of a 65% McIlvaine buffer containing 0.05% triethylamine adjusted to pH 6.4 with phosphoric acid, 18% acetonitrile, and 17% methanol. Xanthonolol was detected at the ultraviolet wavelength 235 nm. The lower limit of quantization was 50 ng/mL. The assay was applied to a pharmacokinetic study in rats. The plasma concentration of xanthonolol versus time data were best fitted to a two-compartment open model with firstorder elimination processes. After the intravenous administration of xanthonolol at three different dosages of 5, 10 and 15 mg/kg, the respective pharmacokinetic parameters, such as apparent volume of distribution, half-life, and clearance, showed no significant difference at three different dosages. Also, the area under the plasma concentration time curves for three dosages increased proportionally with dose. Therefore, the pharmacokinetics of xanthonolol was found to be linear over the dose range studied. 本研究建立一個快速、簡便的高效液相層析方法以定量xanthonolol在大白鼠體內之血中濃度。血液檢品的處理採液相萃取方法，以phenazine為內部標準品，利用碳十八逆相層析管以固定比例之移動相進行分析，移動相之組成包括含有0.05%三乙胺之65% McIlvaine緩衝溶液以磷酸調整酸驗值為6.4，18% 氰甲烷及17% 甲醇，在紫外光源波長235 nm下進行檢測，最低可定量濃度為50ng／mL，並以此條件進行大白鼠體內藥物動力學之分析，由xanthonolol血中濃度對應時間之數據顯示，以具一階次排除過程之二室式開放模式為最適化之動力學模式。Xanthonolol分別以5、10及15 mg／kg三種不同之劑量經靜脈注射給予後，其擬似分佈體積、排除半衰期及出清率等參數在不同劑量下均無顯著性差異，且其血中濃度經時間曲線下面積在三種不同劑量下隨劑量上升呈比例增加，顯示xanthonolol在給予之劑量下於大白鼠體內呈現線性藥物動力學模式。