Mitragynine is a promising candidate for pain relief and opiate replacement but the investigations for drug delivery are lacking. This study aims to investigate the potential of mitragynine to be delivered through the skin with an emphasis on developing and validating a gradient HPLC-UV analytical method to determine mitragynine in the samples collected during in vitro skin permeation studies. The optimised method involves a gradient elution using a C₁₈ column with a mobile phase comprising acetonitrile and 0.1 %v/v of formic acid (0–1 min: 30:70 to 70:30 (v/v) and hold up to 4 min; 4–6 min: return to 30:70 (v/v) and hold up to 10 min) at a flow rate of 1.2 mL/min. This method was validated based on the standards set by the International Council on Harmonisation guidelines. The method showed mitragynine elution at ∼ 4 min with adequate linearity (R² ≥ 0.999 for concentration ranges of 0.5–10 and 10–175 μg/mL) and acceptable limits of detection and quantification at 0.47 and 1.43 μg/mL, respectively. The analytical performance is robust with excellent precision and accuracy. This method was used to evaluate the in vitro skin permeation of mitragynine (5 %w/v) from simple solvent systems over 48 hr. The results showed a cumulative amount of mitragynine permeated at ∼ 11 μg/cm² for dimethyl sulfoxide and ∼ 4 μg/cm² for propylene glycol. The study not only addressed the issues of the currently available HPLC-UV methods that limit the direct application but also affirmed the potential of mitragynine to be delivered through the skin.

Mitragynine 是缓解疼痛和替代阿片类药物的有希望的候选药物，但缺乏对药物输送的研究。本研究旨在调查米特拉甘宁通过皮肤传递的潜力，重点是开发和验证梯度 HPLC-UV 分析方法，以确定体外皮肤渗透研究期间收集的样品中的米特拉甘宁。优化的方法包括使用 C _{18进行梯度洗脱}流动相由乙腈和 0.1 %v/v 甲酸组成的色谱柱（0-1 分钟：30:70 至 70:30 (v/v) 并保持 4 分钟；4-6 分钟：返回 30： 70 (v/v) 并保持 10 分钟），流速为 1.2 mL/min。该方法已根据国际协调委员会指南制定的标准进行了验证。该方法显示 mitragynine 在约 4 分钟时洗脱，具有足够的线性（R ²  ≥ 0.999，浓度范围为 0.5-10 和 10-175 μg/mL），可接受的检测限和定量限分别为 0.47 和 1.43 μg/mL。分析性能稳健，具有出色的精密度和准确度。该方法用于体外评价米特拉甘宁 (5%w/v) 从简单溶剂系统中的皮肤渗透超过 48 小时。结果表明，二甲基亚砜的渗透量为 ～ 11 μg/cm ²，丙二醇的渗透量为 ～ 4 μg/cm ^{2 。}该研究不仅解决了目前可用的 HPLC-UV 方法限制直接应用的问题，而且肯定了米特拉甘宁通过皮肤传递的潜力。