Determination of pKa and Degradation Products of the Mutated BRAF Inhibitor Vemurafenib and UPLC Assay in Human Urine
Senem Şanli *
Department of Chemistry, Faculty of Science and Arts, Uşak University, Uşak, Turkey.
Ayşe Özdemir
Division of Biochemisty, Faculty of Medicine, Uşak University, Uşak, Turkey.
Gülşen Güven
Department of Chemistry, Faculty of Science and Arts, Adnan Menderes University, Aydin, Turkey.
Süleyman Gökçe
Department of Chemistry, Faculty of Science and Arts, Uşak University, Uşak, Turkey.
*Author to whom correspondence should be addressed.
Abstract
In this study, the pKa value of vemurafenib was determined by the dependence of the retention factor on the pH of the mobile phase. The change of pKa in the different acetonitrile fraction ranging between 57.5 and 62.5% (v/v) was studied by using an LC-UV method. Additionally, a simple, reliable, and rapid UPLC method has been developed for the determination of vemurafenib in human urine. Efavirenz was used as an internal standart. For vemurafenib and efavirenz, selectivity factors were found as 1.204. The asymmetry and capacity factors were obtained as 1.100 and 7.532 for vemurafenib.
Vemurafenib was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were detected by LC/MS/MS method.
Keywords: Vemurafenib, UPLC, pKa, degradation products, urine.