title: Use of 4β-hydroxycholesterol in animal and human plasma samples as a biomarker for CYP3A induction.
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 (d7-4βHC) in authentic matrices and chromatographic conditions that showed good separation from isobaric, positional isomers.
  
  
  CONCLUSIONS
  These assays were applied to multiple studies and demonstrated potential applications of 4βHC as a CYP3A biomarker across preclinical and clinical settings.
authors.affiliation: Drug Metabolism & Pharmacokinetics Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Xue
authors.affiliation: Drug Metabolism & Pharmacokinetics Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Drug Metabolism & Pharmacokinetics Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Zeen
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Drug Metabolism & Pharmacokinetics Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Xinqun Irene
authors.initials: XI
authors.lastname: Wu
authors.affiliation: Drug Metabolism & Pharmacokinetics Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Vallejo
authors.affiliation: Drug Metabolism & Pharmacokinetics Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Melo
authors.affiliation: Clinical Pharmacology Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Clinical Pharmacology Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Clinical Pharmacology Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Clinical Pharmacology Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weiss
authors.affiliation: Drug Metabolism & Pharmacokinetics Department, Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Sekhar
authors.initials: S
authors.lastname: Surapaneni
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis*; D004285:Dogs; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D008297:Male; D051379:Mice; D008875:Middle Aged; D051381:Rats; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006888:Hydroxycholesterols; C099828:cholest-5-ene-3,4-diol; D051544:Cytochrome P-450 CYP3A
keywords: 4β-hydroxycholesterol; CYP3A induction; chimeric or humanized mice; cholesterol; drug–drug interaction study; in vitro CYP induction study