Use of 4β-hydroxycholesterol in animal and human plasma samples as a biomarker for CYP3A induction. (February 2016)

• Record Type: Journal Article
• Authors: Xue, Y-J; Hoffmann, Matthew; Tong, Zeen; Wu, Xinqun (Irene); Vallejo, Martha; Melo, Brian; Ye, Ying; Thomas, Michael; Liu, Yong; Weiss, Daniel; Surapaneni, Sekhar
• Is Part Of: Bioanalysis. Volume 8:Number 3(2016)
• Page Start: 215
• Page End: 228
• Publication Date: 2016-02
• Subjects: 4β-hydroxycholesterol -- chimeric or humanized mice -- cholesterol -- CYP3A induction -- drug–drug interaction study -- in vitro CYP induction study; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.15.241
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: 4β-hydroxycholesterol (4βHC) has recently been proposed as a potential endogenous biomarker for CYP3A activity. Developing bioanalytical assays for 4βHC is challenging for several reasons, including endogenous background levels in plasma; the presence of free and ester forms; the inherent lack of MS sensitivity; and the presence of multiple positional isomers.Results: Bioanalytical assays in mouse, rat, dog and human plasma were adapted and modified from a previous published human plasma assay for 4βHC by using alkaline de-esterification, picolinic derivatization, a surrogate analyte ( d 7-4βHC) in authentic matrices and chromatographic conditions that showed good separation from isobaric, positional isomers.Conclusion: These assays were applied to multiple studies and demonstrated potential applications of 4βHC as a CYP3A biomarker across preclinical and clinical settings.