# Photodegradation Assessment of Calicotriol in the Presence of UV Absorbers by UHPLC/MSE
## 1 Introduction  
Calcipotriol (Calcipotriene) is a vitamin D analogue used topically for psoriasis treatment. Psoriasis is a chronic disease characterized by autoimmune and genetic origins, resulting in excessive proliferation of keratinocytes and impaired differentiation [1]. In psoriasis, increased T lymphocyte activity and elevated levels of IL-23 and IL-17 cause inflammation and epidermal hyperplasia [2]. Subclinical inflammation can persist evenafter skin lesions have healed completely, potentially leading to exacerbations of the disease [3]. Psoriasis affects around 2% of the global population and primarily presents as chronic plaque psoriasis in 90% of cases [1]. Typically, the disease manifests with mild symptoms and localized skin lesions, making topical therapy the preferred treatment option [4]. Psoriasis is an incurable condition, and treatment focuses on managing symptoms and improving quality of life [5]. In addition to skin symptoms, psoriasis can cause thick, ridged, or pitted nails. Severe forms of psoriasis, such as generalized pustular psoriasis, may also lead to systemic symptoms like fever, malaise, and fatigue. In addition to cutaneous manifestations, psoriasis is associated with several comorbidities, including psoriatic arthritis (joint pain, stiffness, and swelling), cardiovascular disease, and metabolic syndrome. Early diagnosis and effective management are crucial to reduce disease burden and improve patient outcomes. Psoriasis significantly reduces patients' quality of life, as its unpleasant symptoms and widespread social stigma often lead to emotional distress and feelings of marginalization [6; 7]. For mild to moderate conditions, first-line treatment includes topical corticosteroids, vitamin D analogues, and retinoids. For patients with severe conditions, topical medications are used alongside systemic therapy options such as methotrexate, cyclosporine, and dimethyl fumarate [2]. Corticosteroids are the most common topical treatment for psoriasis; however, the prolonged use of corticosteroids may cause side effects, including corticosteroid-induced skin atrophy, telangiectasia, and tachyphylaxis. The therapeutic efficacy of corticosteroids can be enhanced by the combination with a vitamin D analogue [2; 5]. Medicinal products typically contain calcipotriol (50 \(\upmu\)g/g) and betamethasone dipropionate (0.5 mg/g), which act synergistically. Calcipotriol induces keratinocyte differentiation and inhibits their proliferation. Betamethasone dipropionate exhibits local anti-inflammatory, antipruritic, immunosuppressive, and vasoconstr constrictive properties [2]. In randomized, double-blind clinical trials conducted by [PERSON] et al., a combination of these two substances was shown to be superior to monotherapy with either betamethasone dipropionate or calcipotriol in treating psoriasis vulgaris, demonstrating a faster onset of action [8]. Furthermore, calcipotriol counteracts skin atrophy induced by betamethasone dipropionate [9]. Topical medications containing calcipotriol and betamethasone dipropionate are available in the European Union as gel, ointment, and foam formulations. Among these, the foam formulation is considered particularly innovative due to its enhanced efficacy, improved skin penetration, and greater patient acceptability compared to traditional ointment and gel forms. After applying the foam, the propellants evaporate, leaving a stable, supersaturated solution of calcipotriol and betamethasone without forming crystals [10; 11]. Applying medicinal products to the skin for a local effect facilitates safe use of the drug and reduces the risk of adverse effects. The success of local therapy is determined by reaching the necessary concentration of the active pharmaceutical ingredient at the target location. Medications applied topically are exposed to ultraviolet radiation, which can result in photodegradation of the drug. This process can lead to a reduction in the active substance and the generation of by-products with unknown effects [12; 13].