One of the most challenging goals in modern pharmaceutical research is to develop models that can predict drugs’ behavior, particularly permeability in human tissues. Since the permeability is closely related to the molecular properties, numerous characteristics are necessary in order to develop a reliable predictive tool. The present study attempts to decode the permeability by correlating the apparent permeability coefficient (P_app) of 33 steroids with their properties (physicochemical and structural). The P_app of the molecules was determined by in vitro experiments and the results were plotted as Y variable on a Partial Least Squares (PLS) model, while 37 pharmacokinetic and structural properties were used as X descriptors. The developed model was subjected to internal validation and it tends to be robust with good predictive potential (R²Y = 0.902, RMSEE = 0.00265379, Q²Y = 0.722, RMSEP = 0.0077). Based on the results specific properties (logS, logP, logD, PSA and VD_ss) were proved to be more important than others in terms of drugs P_app. The models can be utilized to predict the permeability of a new candidate drug avoiding needless animal experiments, as well as time and material consuming experiments.

The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the behaviors of vaginal drugs were the main objectives of this study. Franz vertical diffusion cells and different validated HPLC methods were used to measure the permeability of six vaginally administered drugs (econazole, miconazole, metronidazole, clindamycin, lidocaine, and nonoxynol-9). This study was performed (in vitro) on different membranes of polyvinylidene fluoride (PVDF), plain cellulose or cellulose impregnated with isopropyl myristate (IPM), and cellulose combined with PVDF or IPM. The results were compared with those obtained from cow vaginal tissue (ex vivo), where cellulose was proven to be the best simulant. According to the permeability profiles (P_app), the water solubility of the drugs was considered a necessary criterion for their transport in the membranes or in the tissue, while the size was important for their penetration. Furthermore, it was found that polar compounds show clear superiority when penetrating cellulose or tissue, while non-polar ones show superiority when penetrating the lipophilic PVDF membrane. Finally, a successful attempt was made to predict the P_app values (|P_app-predP_app| < 0.005) of the six drugs under study based on a PLS (Partial Least Squares) in silico simulation model.

In order to meet the analytical requirements of the European Medicines Agency (EMA), a new HPLC-FLD method was successfully developed using dansyl chloride for the derivatization and determination of the genotoxic impurities N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) in Lisinopril API and its final product. Samples’ pretreatment includes liquid–liquid microextraction, denitrosation, and derivatization steps. To optimize the process, the parameters contributing to high sensitivity and yielding reliable results were thoroughly studied and optimized using one-factor-at-a-time and experimental design approaches. The analytes were pre-column derivatized with Dansyl-Cl and analyzed by HPLC-fluorescence (λ_em/λ_em = 340/530) using a C₁₈ column and a mixture of phosphate buffer (pH = 2.8; 20 mM)/acetonitrile 55:45 v/v as the mobile phase. The six-level concentration calibration was shown to be linear, with R equal to 0.9995 for both analytes. The limit of detection (LOD) was satisfactory and equal to 4.7 and 0.04 ng/mL for NDMA and NDEA, respectively. Precision was less than 13.4% in all cases, and the average recoveries were equal to 109.2 and 98.1% for NDMA and NDEA, respectively. The proposed procedure is relatively easy, rapid, and suitable for the determination of the two nitrosamines in routine analysis tests.

Homotaurine (HOM) is considered a promising drug for the treatment of Alzheimer’s and other neurodegenerative diseases. In the present work, a new high-performance liquid chromatography with fluorescence detection (HPLC–FLD) (λex. = 340 nm and λem. = 455 nm) method was developed and validated for the study of substance permeability in the central nervous system (CNS). Analysis was performed on a RP-C18 column with a binary gradient elution system consisting of methanol–potassium phosphate buffer solution (pH = 7.0, 0.02 M) as mobile phase. Samples of homotaurine and histidine (internal standard) were initially derivatized with ortho-phthalaldehyde (OPA) (0.01 M), N-acetylcysteine (0.01 M) and borate buffer (pH = 10.5; 0.05 M). To ensure the stability and efficiency of the reaction, the presence of different nucleophilic reagents, namely (a) 2-mercaptoethanol (2-ME), (b) N-acetylcysteine (NAC), (c) tiopronin (Thiola), (d) 3-mercaptopropionic acid (3-MPA) and (e) captopril, was investigated. The method was validated (R² = 0.9999, intra-day repeatability %RSD < 3.22%, inter-day precision %RSD = 1.83%, limits of detection 5.75 ng/mL and limits of quantification 17.43 ng/mL, recovery of five different concentrations 99.75–101.58%) and successfully applied to investigate the in vitro permeability of homotaurine using Franz diffusion cells. The apparent permeability (P_app) of HOM was compared with that of memantine, which is considered a potential therapeutic drug for various CNSs. Our study demonstrates that homotaurine exhibits superior permeability through the simulated blood–brain barrier compared to memantine, offering promising insights for enhanced drug delivery strategies targeting neurological conditions.