Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma
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 inte...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-04-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177915300174 |
| _version_ | 1818728359842021376 |
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| author | Huan Lu Chong Su Lei Yin Liqiang Gu Jingkai Gu Xiaohui Chen |
| author_facet | Huan Lu Chong Su Lei Yin Liqiang Gu Jingkai Gu Xiaohui Chen |
| author_sort | Huan Lu |
| collection | DOAJ |
| description | 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 internal 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., 2.7 μm) 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. |
| first_indexed | 2024-12-17T22:28:45Z |
| format | Article |
| id | doaj.art-efaf0d119143423dad9799596a1fd02e |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-12-17T22:28:45Z |
| publishDate | 2016-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-efaf0d119143423dad9799596a1fd02e2022-12-21T21:30:16ZengElsevierJournal of Pharmaceutical Analysis2095-17792016-04-016211211610.1016/j.jpha.2015.11.006Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasmaHuan Lu0Chong Su1Lei Yin2Liqiang Gu3Jingkai Gu4Xiaohui Chen5School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaResearch Center for Drug Metabolism, College of Life Science, Jilin University, Qianjin Street, Changchun 130012, ChinaResearch Center for Drug Metabolism, College of Life Science, Jilin University, Qianjin Street, Changchun 130012, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaResearch Center for Drug Metabolism, College of Life Science, Jilin University, Qianjin Street, Changchun 130012, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaA 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 internal 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., 2.7 μm) 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.http://www.sciencedirect.com/science/article/pii/S2095177915300174Liquid chromatography–tandem mass spectrometryValproic acid2-enevalproic acid4-enevalproic acid |
| spellingShingle | Huan Lu Chong Su Lei Yin Liqiang Gu Jingkai Gu Xiaohui Chen Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma Journal of Pharmaceutical Analysis Liquid chromatography–tandem mass spectrometry Valproic acid 2-enevalproic acid 4-enevalproic acid |
| title | Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma |
| title_full | Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma |
| title_fullStr | Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma |
| title_full_unstemmed | Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma |
| title_short | Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma |
| title_sort | liquid chromatography tandem mass spectrometry method for simultaneous determination of valproic acid and its ene metabolites in epilepsy patient plasma |
| topic | Liquid chromatography–tandem mass spectrometry Valproic acid 2-enevalproic acid 4-enevalproic acid |
| url | http://www.sciencedirect.com/science/article/pii/S2095177915300174 |
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