Elhennawy Mai Gamal, Lin Hai-Shu
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Pharmaceutics. 2017 Dec 29;10(1):3. doi: 10.3390/pharmaceutics10010003.
Tangeretin (TAN) is a dietary polymethoxylated flavone that possesses a broad scope of pharmacological activities. A simple high-performance liquid chromatography (HPLC) method was developed and validated in this study to quantify TAN in plasma of Sprague-Dawley rats. The lower limit of quantification (LLOQ) was 15 ng/mL; the intra- and inter-day assay variations expressed in the form of relative standard deviation (RSD) were all less than 10%; and the assay accuracy was within 100 ± 15%. Subsequently, pharmacokinetic profiles of TAN were explored and established. Upon single intravenous administration (10 mg/kg), TAN had rapid clearance ( = 94.1 ± 20.2 mL/min/kg) and moderate terminal elimination half-life ( = 166 ± 42 min). When TAN was given as a suspension (50 mg/kg), poor but erratic absolute oral bioavailability (mean value < 3.05%) was observed; however, when TAN was given in a solution prepared with randomly methylated-β-cyclodextrin (50 mg/kg), its plasma exposure was at least doubled (mean bioavailability: 6.02%). It was obvious that aqueous solubility hindered the oral absorption of TAN and acted as a barrier to its oral bioavailability. This study will facilitate further investigations on the medicinal potentials of TAN.
陈皮素（TAN）是一种具有广泛药理活性的膳食多甲氧基黄酮。本研究建立并验证了一种简单的高效液相色谱（HPLC）方法，用于定量测定Sprague-Dawley大鼠血浆中的TAN。定量下限（LLOQ）为15 ng/mL；以相对标准偏差（RSD）表示的日内和日间测定变异均小于10%；测定准确度在100±15%以内。随后，探索并建立了TAN的药代动力学特征。单次静脉注射（10 mg/kg）后，TAN清除迅速（= 94.1±20.2 mL/min/kg），终末消除半衰期适中（= 166±42 min）。当给予TAN混悬液（50 mg/kg）时，观察到绝对口服生物利用度较差且不稳定（平均值< 3.05%）；然而，当给予随机甲基化-β-环糊精配制的溶液中的TAN（50 mg/kg）时，其血浆暴露量至少增加了一倍（平均生物利用度：6.02%）。很明显，水溶性阻碍了TAN的口服吸收，并成为其口服生物利用度的障碍。本研究将有助于进一步研究TAN的药用潜力。
