Centre for Drug Research, Universiti Sains Malaysia, 11800, Penang, Malaysia.
Anal Bioanal Chem. 2010 Jul;397(5):2023-30. doi: 10.1007/s00216-010-3707-7. Epub 2010 May 8.
A new solid phase extraction method for rapid high performance liquid chromatography-UV determination of mitragynine in plasma has been developed. Optimal separation was achieved with an isocratic mobile phase consisting of acetonitrile-ammonium acetate buffer, 50 mM at pH 5.0 (50:50, v/v). The method had limits of detection and quantification of 0.025 and 0.050 microg/mL, respectively. The method was accurate and precise for the quantitative analysis of mitragynine in human and rat plasma with within-day and between-day accuracies between 84.0 and 109.6%, and their precision values were between 1.7 and 16.8%. Additional advantages over known methods are related to the solid phase extraction technique for sample preparation which yields a clean chromatogram, a short total analysis time, requires a smaller amount of plasma samples and has good assay sensitivity for bioanalytical application. The method was successfully applied in pharmacokinetic and stability studies of mitragynine. In the present study, mitragynine was found to be fairly stable during storage and sample preparation. The present study showed for the first time the detailed pharmacokinetic profiles of mitragynine. Following intravenous administration, mitragynine demonstrated a biphasic elimination from plasma. Oral absorption of the drug was slow, prolonged and was incomplete, with a calculated absolute oral bioavailability value of 3.03%. The variations observed in previous pharmacokinetic studies after oral administration of mitragynine could be attributed to its poor bioavailability rather than to the differences in assay method, metabolic saturation or mitragynine dose.
已开发出一种新的固相萃取方法，用于快速高效液相色谱-紫外法测定血浆中的帽柱草碱。采用等度流动相，由乙腈-乙酸铵缓冲液（50 mM，pH 5.0，50:50，v/v）组成，可实现最佳分离。该方法的检测限和定量限分别为 0.025 和 0.050 μg/mL。该方法准确、精密，可用于人及大鼠血浆中帽柱草碱的定量分析，日内和日间准确度在 84.0%至 109.6%之间，精密度值在 1.7%至 16.8%之间。与已知方法相比，该方法的优点还在于固相萃取技术用于样品制备，可得到干净的色谱图，总分析时间短，所需血浆样品量少，且具有良好的生物分析应用检测灵敏度。该方法成功应用于帽柱草碱的药代动力学和稳定性研究。在本研究中，发现帽柱草碱在储存和样品制备过程中相当稳定。本研究首次详细描述了帽柱草碱的药代动力学特征。静脉注射后，帽柱草碱从血浆中呈双相消除。药物口服吸收缓慢、延长且不完全，绝对口服生物利用度值为 3.03%。口服给予帽柱草碱后，先前药代动力学研究中观察到的变化可能归因于其较差的生物利用度，而不是检测方法、代谢饱和或帽柱草碱剂量的差异。
