Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MS<sup>E</sup>

Calcipotriol, a synthetic vitamin D<sub>3</sub> analogue widely used in psoriasis treatment, requires a detailed stability assessment due to its topical application and potential exposure to UV radiation. As a drug applied directly to the skin, calcipotriol is particularly susceptible to...

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Main Authors: Małgorzata Król, Paweł Żmudzki, Adam Bucki, Agata Kryczyk-Poprawa
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Applied Sciences
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Online Access:https://www.mdpi.com/2076-3417/15/15/8124
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author Małgorzata Król
Paweł Żmudzki
Adam Bucki
Agata Kryczyk-Poprawa
author_facet Małgorzata Król
Paweł Żmudzki
Adam Bucki
Agata Kryczyk-Poprawa
author_sort Małgorzata Król
collection DOAJ
description Calcipotriol, a synthetic vitamin D<sub>3</sub> analogue widely used in psoriasis treatment, requires a detailed stability assessment due to its topical application and potential exposure to UV radiation. As a drug applied directly to the skin, calcipotriol is particularly susceptible to photodegradation, which may affect its therapeutic efficacy and safety profile. The present study focuses on the analysis of calcipotriol photostability. An advanced UHPLC/MS<sup>E</sup> method was employed for the precise determination of calcipotriol and its degradation products. Particular attention was given to the effects of commonly used organic UV filters—approved for use in cosmetic products in both Europe and the USA (benzophenone-3, dioxybenzone, meradimate, sulisobenzone, homosalate, and avobenzone)—on the stability of calcipotriol. Unexpected degradation of calcipotriol was observed in the presence of sulisobenzone. Importantly, this effect was consistently detected in methanolic solution and in the pharmaceutical formulation containing calcipotriol and betamethasone, which is particularly significant from a practical perspective. This finding underscores the necessity of evaluating photostability under real-life conditions, as cosmetic ingredients, when co-applied with topical drugs on the skin, may substantially influence the stability profile of the pharmaceutical active ingredient. The research resulted in the first-time characterization of four degradation products of calcipotriol. The degradation process was found to primarily affect the <i>E</i>-4-cyclopropyl-4-hydroxy-1-methylbut-2-en-1-yl moiety, causing its isomerization to the <i>Z</i> isomer and the formation of diastereomers with either the R or S configuration. Computational analyses using the OSIRIS Property Explorer indicated that none of the five degradation products exhibit a toxicity effect, whereas molecular docking studies suggested possible binding of two of the five degradation products of calcipotriol with the VDR.
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institution Kabale University
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spelling doaj-art-25a0f774459d4e259316f2536ef5e5e12025-08-20T03:36:34ZengMDPI AGApplied Sciences2076-34172025-07-011515812410.3390/app15158124Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MS<sup>E</sup>Małgorzata Król0Paweł Żmudzki1Adam Bucki2Agata Kryczyk-Poprawa3Department of Inorganic Chemistry and Pharmaceutical Analytics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, PolandDepartment of Inorganic Chemistry and Pharmaceutical Analytics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, PolandCalcipotriol, a synthetic vitamin D<sub>3</sub> analogue widely used in psoriasis treatment, requires a detailed stability assessment due to its topical application and potential exposure to UV radiation. As a drug applied directly to the skin, calcipotriol is particularly susceptible to photodegradation, which may affect its therapeutic efficacy and safety profile. The present study focuses on the analysis of calcipotriol photostability. An advanced UHPLC/MS<sup>E</sup> method was employed for the precise determination of calcipotriol and its degradation products. Particular attention was given to the effects of commonly used organic UV filters—approved for use in cosmetic products in both Europe and the USA (benzophenone-3, dioxybenzone, meradimate, sulisobenzone, homosalate, and avobenzone)—on the stability of calcipotriol. Unexpected degradation of calcipotriol was observed in the presence of sulisobenzone. Importantly, this effect was consistently detected in methanolic solution and in the pharmaceutical formulation containing calcipotriol and betamethasone, which is particularly significant from a practical perspective. This finding underscores the necessity of evaluating photostability under real-life conditions, as cosmetic ingredients, when co-applied with topical drugs on the skin, may substantially influence the stability profile of the pharmaceutical active ingredient. The research resulted in the first-time characterization of four degradation products of calcipotriol. The degradation process was found to primarily affect the <i>E</i>-4-cyclopropyl-4-hydroxy-1-methylbut-2-en-1-yl moiety, causing its isomerization to the <i>Z</i> isomer and the formation of diastereomers with either the R or S configuration. Computational analyses using the OSIRIS Property Explorer indicated that none of the five degradation products exhibit a toxicity effect, whereas molecular docking studies suggested possible binding of two of the five degradation products of calcipotriol with the VDR.https://www.mdpi.com/2076-3417/15/15/8124calcipotriol calcipotrienedrugs photostabilityUV absorbersvitamin D analogspsoriasis
spellingShingle Małgorzata Król
Paweł Żmudzki
Adam Bucki
Agata Kryczyk-Poprawa
Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MS<sup>E</sup>
Applied Sciences
calcipotriol calcipotriene
drugs photostability
UV absorbers
vitamin D analogs
psoriasis
title Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MS<sup>E</sup>
title_full Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MS<sup>E</sup>
title_fullStr Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MS<sup>E</sup>
title_full_unstemmed Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MS<sup>E</sup>
title_short Photodegradation Assessment of Calcipotriol in the Presence of UV Absorbers by UHPLC/MS<sup>E</sup>
title_sort photodegradation assessment of calcipotriol in the presence of uv absorbers by uhplc ms sup e sup
topic calcipotriol calcipotriene
drugs photostability
UV absorbers
vitamin D analogs
psoriasis
url https://www.mdpi.com/2076-3417/15/15/8124
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AT pawełzmudzki photodegradationassessmentofcalcipotriolinthepresenceofuvabsorbersbyuhplcmssupesup
AT adambucki photodegradationassessmentofcalcipotriolinthepresenceofuvabsorbersbyuhplcmssupesup
AT agatakryczykpoprawa photodegradationassessmentofcalcipotriolinthepresenceofuvabsorbersbyuhplcmssupesup