###### Abstract
Taking into account that the five active ingredients work synergistically, meaning that their therapeutic, healing, and regenerative properties are either complementary or additive, it is recommended to combine them in cosmetic formulations in order to achieve the optimal result. Their suggested percentage composition in cosmetics is for ferulic acid 0.5-1% [20], for resveratrol up to 5%, for quercetin 0.1-3, up to 0.3% for retinol [21], and up to 5% [22] for vitamin E. Therefore, in the context of the present work, a new formulation was prepared and then evaluated, incorporating the five active ingredients. The formulation belongs to the cold cream category, i.e., it is a water-in-oil (\(w/o\)) emulsion with a greasy texture that ensures prolonged contact at the application surface, compared to other semi-solid forms. Cold cream helps restore moisture to dry skin by creating a feeling of coolness due to the evaporation of water. In addition, it is non-irritating, and when applied to the skin, it provides softness. From an analytical point of view, chromatography is considered the method of choice for the reliable determination and suitability of such formulations. Most analyses reporting individually to one of these active ingredients (ferulic acid, resveratrol, quercetin, retinol, andtocopherol) are performed with HPLC or high-performance thin-layer chromatography (HPTLC) or even gas chromatography [23; 24; 25; 26; 27; 28; 29]. Their separation conditions may vary depending on the study and the substrate. In HPLC, usually RP-C\({}_{18}\)[30; 31] or C\({}_{8}\)[32] columns are used as stationary phases, and water with organic solvents, such as acetonitrile and/or methanol and ethanol, is preferred as mobile phases [33; 34]. It is noteworthy that although the five active ingredients (APIs) are widely used in cosmetics, to the best of our knowledge, there is no literature report for their simultaneous determination, which makes the present study innovative. The only related mention is an HPLC-UV method suitable for the determination of QR, RTN, and \(\alpha\)-TOC in nanoemulsion [35]. Relevant analyses have also been described for their binary mixtures, such as that of quercetin with resveratrol [32], retinol with tocopherol [36], or tocopherol with quercetin [37]. Thus, in the present work, five active ingredients were determined in cold cream (\(w/o\)) using a new validated HPLC-DAD method. Due to the complex substrate, the processing of the samples was investigated by experimental design methodology (D-Optimal cross) [38; 39]. API's stability (at 45 \({}^{\circ}\)C and sonication) was also studied over a period of 80 min. Finally, the same analytical method was applied for the in vitro permeation study of the five drugs using Franz cells. Their behavior was compared after being incorporated into a simple suspension and a cream. Samples after lyophilization were reconstituted and analyzed. A new formulation with anti-aging properties is proposed to contribute to the scientific community's efforts to combat aging. For the analysis of its five active ingredients, an innovative, reliable, and flexible analytical method suitable for routine analysis is developed.