The Role of the Therapeutic Drug Monitoring When Using Antiepileptic Drugs

Yakunina, A. V.; Повереннова, И. Е.

doi:10.17749/2077-8333.2016.8.3.066-073

Cited by 2 publications

(1 citation statement)

References 2 publications

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“…Although dosing recommendations for many psychotropic medications, including VPA, are being developed based on PGx results, the valproates are prescribed to patients with psychiatric disorders who have not undergone predictive PGx and/or genetic screening [103,104]. TDM of plasma levels of VPA has been used in neurology and psychiatry for a long time [105]. This diagnostic method takes into account all factors of interindividual variability in the metabolism of VPA and other psychotropic drugs.…”

Section: Discussionmentioning

confidence: 99%

Ethnic Aspects of Valproic Acid P-Oxidation

Shnayder,

Grechkina,

Trefilova

et al. 2024

Biomedicines

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The safety of the use of psychotropic drugs, widely used in neurological and psychiatric practice, is an urgent problem in personalized medicine. This narrative review demonstrated the variability in allelic frequencies of low-functioning and non-functional single nucleotide variants in genes encoding key isoenzymes of valproic acid β-oxidation in the liver across different ethnic/racial groups. The sensitivity and specificity of pharmacogenetic testing panels for predicting the rate of metabolism of valproic acid by P-oxidation can be increased by prioritizing the inclusion of the most common risk allele characteristic of a particular population (country).

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Section: Discussionmentioning

confidence: 99%

Ethnic Aspects of Valproic Acid P-Oxidation

Shnayder,

Grechkina,

Trefilova

et al. 2024

Biomedicines

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Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma

Malygin¹,

Popov²,

Демидова³

et al. 2018

Èpilepsiâ paroksizmalʹnye sostoâ.

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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.

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The Role of the Therapeutic Drug Monitoring When Using Antiepileptic Drugs

Cited by 2 publications

References 2 publications

Ethnic Aspects of Valproic Acid P-Oxidation

Ethnic Aspects of Valproic Acid P-Oxidation

Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma

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