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A Highly Sensitive Liquid Chromatography–Electrospray Ionization–Time of Flight/Mass Spectrometric Assay for the Quantitation of 4-Beta-Hydroxycholesterol and Its Application to in vivo Cytochrome P450 3a Induction by AGM-130.
- Source :
-
Journal of Liquid Chromatography & Related Technologies . 2015, Vol. 38 Issue 18, p1675-1680. 6p. 2 Diagrams, 2 Charts, 2 Graphs. - Publication Year :
- 2015
-
Abstract
- A liquid chromatography–electrospray ionization-time-of-flight/mass spectrometry (LC–ESI-TOF/MS) method was developed for the determination of 4-beta-hydroxycholesterol (4β-HC) in rat plasma, to evaluate cytochrome P450 3A (CYP3A) induction liability of a novel cyclin dependent kinases (CDKs) inhibitor, AGM-130. The method consisted of sample preparation without derivatization reagents for high sensitivity such as picolinyl ester, which could be labor-intensive and time consuming. The 4% bovine serum albumin in phosphate-buffered saline as a surrogate matrix was used in the calibration curve and quality control samples for the determination of 4β-HC. Stable isotope-labeled (SIL) 4β-HC (d7-4β-HC) was used as an internal standard. A quadratic regression (weighted 1/concentration), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range of 3.01–2220 ng/mL for 4β-HC. For quality control samples at 15.0, 165, and 1820 ng/mL from the qualification experiment, the within-run accuracy ranged from 95% to 105% with precision values ≤10% for 4β-HC. This novel LC–ESI-TOF/MS method was successfully applied to evaluate the potential of CYP3A induction by 5′-hydroxy-5-nitro-indirubin oxime (AGM-130) in rat. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10826076
- Volume :
- 38
- Issue :
- 18
- Database :
- Academic Search Index
- Journal :
- Journal of Liquid Chromatography & Related Technologies
- Publication Type :
- Academic Journal
- Accession number :
- 110931716
- Full Text :
- https://doi.org/10.1080/10826076.2015.1091009