The retention and lipophilicity characteristics of four oral antidiabetic drugs namely; Metformin (MET), Linagliptin (LIN), Empagliflozin (EMP), and Dapagliflozin (DAP) were evaluated by a facile TLC-spectrodensitometric method. The developed method was validated and employed for simultaneous determination of the investigated drugs in their synthetic quaternary mixture, single- and multi-component tablets, and human plasma. The separation of the cited drugs was achieved using silica gel G 60F₂₅₄-TLC plates and a mobile system consisting of n-butanol: water: glacial acetic acid (7: 3: 1, v/v/v). After scanning at 234 nm, good linearities (10.0–2000.0 ng/band for each drug) and correlation coefficients (r = 0.99882–0.99972) with lower limits of detection and quantitation (2.17–3.58 and 6.57–10.85 ng/band, respectively) were statistically calculated. The obtained recoveries (98.35–101.38%) proved the wide applicability of the established method for concurrent estimation of the studied antidiabetics in fixed-dose combination tablets and human plasma. Besides, the present work was extended to estimate the lipophilicity parameters of the targeted drugs. Molecular lipophilicity (R_M), relative lipophilicity (R_M0), and lipophilic descriptor (C₀) were calculated for MET, LIN, EMP, and DAP. Good correlations (r = 0.8729–0.9933) between the chromatographic retention data and molecular descriptors of the studied drugs were attained. The obtained results confirmed the poor lipophilicity of MET and LIN compared to EMP and DAP. Lastly, understanding the lipophilicity of the cited drugs may be promising for the future design of safer and more effective formulations for diabetes mellitus, cancer, and Alzheimer’s disease. Over and above, this work may be further applied to QSAR studies.

四种口服降糖药的滞留​​性和亲脂性特点；二甲双胍 (MET)、利格列汀 (LIN)、恩格列净 (EMP) 和达格列净 (DAP) 通过简便的 TLC 分光光密度法进行评估。所开发的方法经过验证并用于同时测定合成四元混合物、单组分和多组分片剂以及人血浆中的研究药物。使用硅胶 G 60F _{254实现了引用药物的分离}-TLC 板和由正丁醇组成的移动系统：水：冰醋酸（7:3:1，v/v/v）。在 234 nm 扫描后，良好的线性（每种药物为 10.0-2000.0 ng/波段）和相关系数（r = 0.99882-0.99972）具有较低的检测限和定量限（分别为 2.17-3.58 和 6.57-10.85 ng/波段）进行了统计计算。获得的回收率 (98.35–101.38%) 证明了所建立的方法在同时估计固定剂量复方片剂和人血浆中研究的抗糖尿病药物的广泛适用性。此外，目前的工作扩展到估计靶向药物的亲脂性参数。分子亲油性 (R _M )、相对亲油性 (R _M0 ) 和亲油性描述符 (C ₀) 计算 MET、LIN、EMP 和 DAP。在色谱保留数据和所研究药物的分子描述符之间获得了良好的相关性（r = 0.8729–0.9933）。所得结果证实与 EMP 和 DAP 相比，MET 和 LIN 的亲脂性较差。最后，了解所引用药物的亲脂性可能有助于未来设计更安全、更有效的糖尿病、癌症和阿尔茨海默病制剂。除此之外，这项工作可能会进一步应用于 QSAR 研究。