## 1 Introduction  
Polyphenols are substances with numerous useful nutritional and pharmaceutical properties [1]. Quercetin (Q) or 3,3\({}^{\prime}\)A\({}^{\prime}\),5,7-pentahydroflavone is one of the most abundant plant flavonoids in nature and has been the focus of numerous biomedical studies in the last decade for its anti-inflammatory, anticancer, protective and preventive therapeutic properties for heart health, and low systemic toxicity [2, 3, 4, 5]. It has also recently been shown to have inhibitory activity against SARS-CoV [6]. Resveratrol (R), or 3,5,4-trihydroxystilbene,is a non-flavonoid phenol, naturally produced by various plants to protect against stressful situations, such as fungal or bacterial infections, injury, and exposure to ultraviolet rays [7; 8; 9]. Resveratrol may exert a protective effect on the central nervous system and is associated with a reduced risk of cardiovascular disease, diabetes, and Alzheimer's disease and it has anti-aging effects [7; 10; 11; 12]. In addition, it may play an important role in the inhibition, promotion, and progression of multistage carcinogenesis [7; 10; 11]. Q and R have been proposed, alone and in combination, as components of formulations for important therapeutic applications, such as in the treatment of colorectal cancer [13; 14; 15; 16]. However, a serious obstacle to their pharmacological use [16] is represented by their rapid metabolism in humans. Slow-release nano-formulations have been recommended to improve their pharmacokinetics and prolong their benefits in the treatment of neoplasms [16]. Grapes, particularly their skins, and grape-derived products such as wine, are among the most significant dietary sources of R [1; 8]. Similarly, Q is abundantly found in fruits and vegetables, with notable concentrations in apples, grapes, medicinal herbs, and various fruit waste materials [17; 18; 19; 20]. These compounds are recognized as potent antioxidants, making grape and wine waste a valuable resource for extracting both Q and R.  
Given the importance of these natural antioxidants in food supplements and pharmaceutical applications, numerous analytical methods have been developed for their determination in various matrices, including grapes, wine, and winemaking by-products. Among these, liquid chromatography (LC) coupled with ultraviolet (UV) detection is the most widely used technique due to its affordability and accessibility for most laboratories [20; 21; 22; 23; 24]. Additionally, fluorescence detection (FLD) and mass spectrometry (MS) have been successfully employed for the quantification of Q and R in food samples, offering higher sensitivity and selectivity [23; 24; 25; 26]. Other techniques, such as thin-layer chromatography (TLC), gas chromatography (GC), capillary electrophoresis (CE), and electrochemical methods, have also been utilized for their determination, though to a lesser extent [23; 24; 27]. For the extraction of Q and R from winemaking waste, solid-liquid extraction (SLE) and supercritical fluid extraction (SFE) are commonly employed. However, these methods are often labor-intensive, costly, and require significant amounts of organic solvents, which can limit their practicality and sustainability [20; 23; 24]. As a result, there is a growing interest in developing more efficient and environmentally friendly extraction techniques to optimize the recovery of these valuable antioxidants. Solid phase microextraction (SPME) is a fast and sensitive sample preparation technology that uses a fiber coated with a suitable polymer extraction phase to concentrate different analytes present in a liquid, solid, or gaseous sample [28]. The most typical uses include environmental, food, forensic and toxicological analyses for the search for contaminants, aromas, odors, and drugs, even at the trace level in aqueous or gaseous matrices [29], as well as pharmacokinetic studies, therapeutic drug monitoring, biomarker discovery, and targeted and untargeted metabolomics [30; 31; 32; 33].