## 1 Introduction  
Resveratrol (_trans_-4,3',5'-trihydroxystilbene) is a natural compound found in grapes and in many other medicinal plants [1]. Resveratrol acts as phytoalexin protecting the plant against virus infections. The high concentration of this compound in red wine is attributed to its high concentration in the skin of red grapes [2]. Resveratrol (C\({}_{14}\)H\({}_{12}\)O\({}_{3}\)) is a whitish color powder with a molecular weight of 228.25 g/mol, its solubility varies from 0.03 g/L in water to 16 g/L in DMSO and 50 g/L in ethanol. Its melting point ranges from 253 to 255 \({}^{\circ}\)C, exhibiting a log P of 3.1 [3, 4]. Although poorly water soluble, resveratrol shows high membrane permeability and may be considered as a Class II of the Biopharmaceutics Classification System (BCS) [3, 5]. Besides its glycoside form, resveratrol occurs in the _cis_-(Z) and _trans_-(E) structural isomers, which exhibit distinct biological effects [6, 7]. Ultraviolet (UV) radiation induces partial conversion of _trans_-(E) isomer into _cis_-(Z), resulting in a mix of the two isomers (Figure 1) [8]. From the perspective of nutraceutical applications [9, 10, 11, 12, 13, 14, 15, 16, 17], research is being demonstrating that _trans_-resveratrol (tRES) offers many health benefits e.g., as it: (i) lowers the risk of cardiovascular complications [18, 19], (ii) protects the human body against retinal ischemia by downregulating matrix metalloproteinase-9 expression by nitric oxide and by upregulating heme oxygenase-1 [20]; (iii) improves cells sensitivity to insulin, reducing oxidative stress, and activating protein kinase B pathway in type 2 diabetic patients [21, 22, 23]; (iv) acts as a therapeutic agent for neurodegenerative diseases e.g., in Alzheimer's disease, Parkinson's disease, or multiple sclerosis [24, 25]; (v) modulates inflammatory arthritis by selectively suppressing key cellular and humoral responses required for disease settling [26]; (vi) inhibits platelet aggregation and synthesis of thromboxane B2 and hydroxyl heptadecatrienoate (HHT) [27]; (vii) exhibits antiherpetic activity [28] and (viii) chemopre properties [29]. Scientific literature describes the encapsulation of tRES in different types of lipid nanoparticles [4, 30, 31], which have demonstrated to be taken up by cells [32], and accumulated around nuclei. [PERSON] et al. [33] showed that tRES concentration was greatly increased in the target tissue when tRES-loaded nanoparticles were injected [33]. Moreover, tRES-loaded nanoparticles promoted greater tumor growth inhibition. [PERSON] et al. [34] demonstrated that tRES loaded in PEGylated polymeric nanoparticles based on polylactic acid cores (PEG-PLA, of MW 5000:5000) exhibited in vitro and in vivo antitumor effects such as the dose-dependent reduction of cell viability, the suppression of glucose metabolism, improved animal survival, and reduced tumor volume. Among the several types of nanoparticles, solid lipid nanoparticles (SLN) have been showing high physical stability, biodegradability, and biocompatibility for a set of administration routes [35, 36], the potential to modify the release kinetics of loaded drugs [37, 38], as well as potential for crossing the cellular membrane and to accumulate in the perinuclear region without toxic effect [39, 40]. Methods commonly used for the quantification of resveratrol when loaded in nanoparticles do not promote the separation of the isoforms (_trans_- and _cis_-) of the drug. Furthermore, a monograph of tRES in official compendia is not yet available. For this purpose, the validation of a suitable quantitative method for this drug becomes a demand, for which the first step is to identify the critical parameters and to establish the acceptance criteria [41].