Adehin Ayorinde, Tan Keai Sinn, Tan Wen
Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
Curr Ther Res Clin Exp. 2019 Jun 22;91:1-4. doi: 10.1016/j.curtheres.2019.06.003. eCollection 2019.
Isosteviol is a synthetic derivative of steviol glycosides with promising pharmacological properties and might find future use as a cardioprotective agent.
A simple LC-MS/MS technique was developed and validated for the bioanalysis of isosteviol in plasma and erythrocytes. This method was subsequently utilized for the in vitro assessment of isosteviol's partitioning into blood compartments of humans and rats.
Fresh blood samples from healthy humans and Wistar rats were equilibrated with 1, 10, and 30 µM isosteviol at 37 °C in a shaking dry-bath. The levels of isosteviol in plasma and erythrocytes partitions were determined in these samples, after separation, at intervals over a 60-minute period. The data derived was used to estimate erythrocyte-to-plasma and blood-to-plasma coefficients.
Mean erythrocyte-to-plasma partition coefficients (SD) after 60 minutes of equilibration were observed to be 0.039 (0.002) and 0.040 (0.003) in humans and rats, respectively. Derived values for the blood-to-plasma ratio (SD) were 0.576 (0.001) in humans and 0.543 (0.007) in rats, whereas plasma component binding was estimated to be more than 96%.
The findings suggest that isosteviol preferentially partitions into plasma compartments in humans and rats. The significance of this profile for the efficacy, tissue uptake, and retention of isosteviol will have to be further studied.
异甜菊醇是甜菊糖苷的一种合成衍生物，具有良好的药理特性，未来可能用作心脏保护剂。
开发并验证一种简单的液相色谱-串联质谱（LC-MS/MS）技术，用于血浆和红细胞中异甜菊醇的生物分析。随后，该方法被用于体外评估异甜菊醇在人和大鼠血液各组分中的分配情况。
将来自健康人和Wistar大鼠的新鲜血液样本在37°C的振荡干浴中与1、10和30 μM的异甜菊醇平衡。在分离后，于60分钟内每隔一段时间测定这些样本中血浆和红细胞组分中异甜菊醇的水平。所得数据用于估算红细胞与血浆以及血液与血浆的系数。
平衡60分钟后，观察到人和大鼠的平均红细胞与血浆分配系数（标准差）分别为0.039（0.002）和0.040（0.003）。计算得出的血液与血浆比值（标准差）在人中为0.576（0.001），在大鼠中为0.543（0.007），而血浆成分结合率估计超过96%。
研究结果表明，异甜菊醇在人和大鼠中优先分配到血浆组分中。这种分布情况对异甜菊醇的疗效、组织摄取和滞留的意义还有待进一步研究。
