Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma
Aim: to adapt the HPLC-MS/MS technique to determining valproic acid and its metabolites in blood plasma for drug therapy monitoring.Materials and Methods: The chromatographic assay was run using an Agilent 1260 Infinity II chromatograph with a Phenomenex synergi Fusion analytical column 4 μm-C18 2×5...
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| Format: | Article |
| Language: | Russian |
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IRBIS LLC
2018-08-01
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| Series: | Эпилепсия и пароксизмальные состояния |
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| Online Access: | https://www.epilepsia.su/jour/article/view/407 |
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| author | A. S. Malygin N. S. Popov M. A. Demidova M. N. Kudrayshova |
| author_facet | A. S. Malygin N. S. Popov M. A. Demidova M. N. Kudrayshova |
| author_sort | A. S. Malygin |
| collection | DOAJ |
| description | Aim: to adapt the HPLC-MS/MS technique to determining valproic acid and its metabolites in blood plasma for drug therapy monitoring.Materials and Methods: The chromatographic assay was run using an Agilent 1260 Infinity II chromatograph with a Phenomenex synergi Fusion analytical column 4 μm-C18 2×50 mm. The mobile phase consisted of 0.1% ammonium acetate in distilled water and 0.1% ammonium acetate in methanol (10:90 v/v, 0.5 ml/min). The multiple ions monitoring (MIM) mode was used for mass- spectrometric detection of valproic acid at m/z = 143.1, with the negative ion mode. The method was found applicable over the range from 1 mcg/ml to 200 mcg/ml of valproic acid. For the mass spectroscopy detection of valproic acid metabolites, the multiple reaction monitoring (MRM mode) was used. MS identifications of 2-propyl-4-pentanoil-β-О-glucuronide; 2-propyl-4-pentenoic acid, 3-hydroxy-2- propylpentanoic acid, 4-hydroxy-2-propylpentanoic acid, 2-propylglutaric acid and 3- oxo-2-propylpentanoic acid in the negative ion mode were carried out at m/z 319.2→143.2; m/z 140.1→140.1; m/z 159.1→101; m/z 159.1→123.1; m/z 173→129.1 and m/z 157.05→11, respectively. The method was sensitive over the range from 10 ng/ml to 500 ng/ml of the tested compounds.Results: The developed technique allows for determining valproic acid and its metabolites in a single sample; thus, the preliminary stage of separate sample preparation can be omitted, which increases the informative value of the assay without increasing its cost.Conclusion: This innovative methodology for the quantification of valproic acid and its metabolites in the blood plasma is expected to facilitate the individual approach to the treatment of patients with epilepsy, thereby increasing the efficacy and safety of the pharmacotherapy. |
| format | Article |
| id | doaj-art-9bf68a6915df4ff382eb9781edba8383 |
| institution | DOAJ |
| issn | 2077-8333 2311-4088 |
| language | Russian |
| publishDate | 2018-08-01 |
| publisher | IRBIS LLC |
| record_format | Article |
| series | Эпилепсия и пароксизмальные состояния |
| spelling | doaj-art-9bf68a6915df4ff382eb9781edba83832025-08-20T02:54:04ZrusIRBIS LLCЭпилепсия и пароксизмальные состояния2077-83332311-40882018-08-01102354210.17749/2077-8333.2018.10.2.035-042394Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasmaA. S. Malygin0N. S. Popov1M. A. Demidova2M. N. Kudrayshova3Tver State Medical UniversityTver State Medical UniversityTver State Medical UniversityTver State Medical UniversityAim: to adapt the HPLC-MS/MS technique to determining valproic acid and its metabolites in blood plasma for drug therapy monitoring.Materials and Methods: The chromatographic assay was run using an Agilent 1260 Infinity II chromatograph with a Phenomenex synergi Fusion analytical column 4 μm-C18 2×50 mm. The mobile phase consisted of 0.1% ammonium acetate in distilled water and 0.1% ammonium acetate in methanol (10:90 v/v, 0.5 ml/min). The multiple ions monitoring (MIM) mode was used for mass- spectrometric detection of valproic acid at m/z = 143.1, with the negative ion mode. The method was found applicable over the range from 1 mcg/ml to 200 mcg/ml of valproic acid. For the mass spectroscopy detection of valproic acid metabolites, the multiple reaction monitoring (MRM mode) was used. MS identifications of 2-propyl-4-pentanoil-β-О-glucuronide; 2-propyl-4-pentenoic acid, 3-hydroxy-2- propylpentanoic acid, 4-hydroxy-2-propylpentanoic acid, 2-propylglutaric acid and 3- oxo-2-propylpentanoic acid in the negative ion mode were carried out at m/z 319.2→143.2; m/z 140.1→140.1; m/z 159.1→101; m/z 159.1→123.1; m/z 173→129.1 and m/z 157.05→11, respectively. The method was sensitive over the range from 10 ng/ml to 500 ng/ml of the tested compounds.Results: The developed technique allows for determining valproic acid and its metabolites in a single sample; thus, the preliminary stage of separate sample preparation can be omitted, which increases the informative value of the assay without increasing its cost.Conclusion: This innovative methodology for the quantification of valproic acid and its metabolites in the blood plasma is expected to facilitate the individual approach to the treatment of patients with epilepsy, thereby increasing the efficacy and safety of the pharmacotherapy.https://www.epilepsia.su/jour/article/view/407hplc-ms/msantiepileptic drugsvalproic acidmetabolitesdrug therapy monitoring. |
| spellingShingle | A. S. Malygin N. S. Popov M. A. Demidova M. N. Kudrayshova Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma Эпилепсия и пароксизмальные состояния hplc-ms/ms antiepileptic drugs valproic acid metabolites drug therapy monitoring. |
| title | Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma |
| title_full | Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma |
| title_fullStr | Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma |
| title_full_unstemmed | Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma |
| title_short | Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma |
| title_sort | chromatography tandem mass spectrometry hplc ms ms for the detection of valproic acid and its metabolites in blood plasma |
| topic | hplc-ms/ms antiepileptic drugs valproic acid metabolites drug therapy monitoring. |
| url | https://www.epilepsia.su/jour/article/view/407 |
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