Determination of 7α-OH cholesterol by LC–MS/MS: Application in assessing the activity of CYP7A1 in cholestatic minipigs
- Source:
- Journal of chromatography 2016 v.1025 pp. 76-82
- ISSN:
- 1570-0232
- Subject:
- acetonitrile, cholesterol, chromatography, formic acid, liver, liver microsomes, miniature swine
- Abstract:
- An LC–MS/MS method was developed and validated to determine 7α-OH cholesterol in liver microsome. This method was convenient and fast with high specificity and sensitivity. Briefly, a gradient elution was performed on a Synergi polar-C18 column (50×4.6mm i.d., 3μm). The mobile phase (consisting of 0.1% HCOOH solution and acetonitrile) eluted in gradient at a flow rate of 1ml/min. MS detection was operated on APCI (+) mode; the MRM transitions for 7α-OH cholesterol and D7-cholesterol (I.S.) were 385.1≥159.1 and 376.4≥266.3, respectively. The linear response range of 7α-OH cholesterol was covered from 1.563 to 100.0ng/ml. All of the validation items meet the requirement of FDA guidance for bioanalytical method validation. This method was applied to enzymatic studies for determination of cholesterol 7alpha-hydroxylation activity catalyzed by CYP7A1 in the cholestatic minipigs liver microsomes.
- Agid:
- 62878
- Handle:
- 10113/62878
- https://doi.org/10.1016/j.jchromb.2016.05.005