Faculty of Pharmacy, Philadelphia University, Amman, Jordan.
School of Pharmacy, University of Jordan, Amman, Jordan.
PLoS One. 2021 Mar 17;16(3):e0247879. doi: 10.1371/journal.pone.0247879. eCollection 2021.
The focus of this research was to develop and validate a suitable HPLC method, which allows simultaneous determination of three proposed skin model penetrants to investigate the percutaneous diffusion behavior of their combination: caffeine, methyl paraben and butyl paraben. These penetrants were selected because they represent a wide range of lipophilicities. This model highlights the effect of combining penetrants of different molecular properties on their diffusion behavior through skin. The proposed method employed a gradient system that was systematically optimized for separation and quantification of the penetrants. The effect of the stationary phase (C18, C4 and cyano (CN)) was assessed with CN proven to be superior in terms of peak shape, retentivity and dynamic linear range. Significant differences in retention time, peak broadening, and quantifiability between different stationary phases could be demonstrated. The method was validated as per ICH guidelines Q2 (R1) with a satisfactory outcome. The method was successfully applied for real diffusion experiments, and revealed notable differences between the individual penetrants and their ternary mixture on transdermal permeation. The method could potentially be extended to determine these analytes in other related skin permeation investigations.
本研究的重点是开发和验证一种合适的 HPLC 方法，该方法能够同时测定三种拟议的皮肤模型渗透剂，以研究它们组合的经皮扩散行为：咖啡因、对羟基苯甲酸甲酯和对羟基苯甲酸丁酯。选择这些渗透剂是因为它们代表了广泛的亲脂性。该模型突出了不同分子特性的渗透剂组合对其通过皮肤扩散行为的影响。所提出的方法采用了梯度系统，该系统经过系统优化，可用于分离和定量渗透剂。评估了固定相（C18、C4 和氰基（CN））的效果，结果表明 CN 在峰形、保留性和动态线性范围方面具有优越性。可以证明不同固定相之间在保留时间、峰展宽和定量能力方面存在显著差异。该方法按照 ICH 指南 Q2（R1）进行了验证，结果令人满意。该方法成功应用于实际扩散实验，揭示了单个渗透剂及其三元混合物在透皮渗透方面的显著差异。该方法有可能扩展到其他相关皮肤渗透研究中测定这些分析物。
