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Modification of gradient HPLC method for determination of small molecules' affinity to human serum albumin under column safety conditions: Robustness and chemometrics study
Abstrakt
In the early stages of drug discovery, beyond the biological activity screening, determining the physicochemical properties that affect the distribution of molecules in the human body is an essential step. Plasma protein binding (PPB) is one of the most important investigated endpoints. Nevertheless, the methodology for measuring %PPB is significantly less popular and standardized than other physicochemical properties, like lipophilicity. Here, we proposed how to modify protocols presented by Valko into column safety conditions and evaluated their robustness using fractional factorial design. For robustness testing, four factors were selected: column temperature, mobile phase flow rate, maximum isopropanol concentration in the mobile phase, and buffer pH. Elaborate methods have been applied for the analysis of HSA affinity for three groups of antibiotic-oriented substances that vary in chemical structure: fluoroquinolones, sulfonamides, and tetrazole derivatives. Furthermore, based on the reversed-phase chromatography the workflow of pilot studies was proposed to select molecules that have high affinity to HSA and can not be eluted from the HSA column using the concentration of organic modifier recommended by the column manufacturer
Cytowania
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4
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Autorzy (10)
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Mateusz Woziński
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Katarzyna Greber
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Monika Pastewska
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Piotr Kolasiński
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Beata Żołnowska
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Jarosław Sławiński
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Daniel Szulczyk
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Wiesław Sawicki
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Krzesimir Ciura
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Informacje szczegółowe
- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuły w czasopismach
- Opublikowano w:
-
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
nr 239,
ISSN: 0731-7085 - Język:
- angielski
- Rok wydania:
- 2024
- Opis bibliograficzny:
- Woziński M., Greber K., Pastewska M., Kolasiński P., Hewelt-Belka W., Żołnowska B., Sławiński J., Szulczyk D., Sawicki W., Ciura K.: Modification of gradient HPLC method for determination of small molecules' affinity to human serum albumin under column safety conditions: Robustness and chemometrics study// JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS -Vol. 239, (2024), s.115916-
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1016/j.jpba.2023.115916
- Źródła finansowania:
-
- Publikacja bezkosztowa
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 75 razy
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