Liquid chromatography-tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma$
10.1016/j.jpha.2015.11.006
- Author:
Huan LU
;
Chong SU
;
Lei YIN
;
Liqiang GU
;
Jingkai GU
;
Xiaohui CHEN
- Publication Type:Journal Article
- Keywords:
Liquid chromatography-tandem mass spectrometry;
Valproic acid;
2-enevalproic acid;
4-enevalproic acid
- From:
Journal of Pharmaceutical Analysis
2016;6(2):112-116
- CountryChina
- Language:Chinese
-
Abstract:
A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography–tandem mass spectrometry. Probenecid was used as in-ternal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C18 column (50 mm ? 4.6 mm i.d., 2.7μm) by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 min. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0-143.0 for valproic acid, m/z 140.9-140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9-239.9 for probenecid. The results showed good linearity of valproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges. The correlation coefficients were more than 0.998. The intra- and inter-day precision of the assay was less than 11.0%and the accuracy ranged from 2%to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring.
