Tag Archives: valproic acid

Protective effect of Vitamin C against valproic acid on liver: Histological and biochemical changes on local rabbits

Taghreed Hazem Al-Fakje, Faehaa A. Al-Mashhadane, Maha Khaled Yusuf, Faris Ghanim Al-Taee

Department of Dental Basic Sciences College of Dentistry, University of Mosul, Mosul, Iraq

DOI: 10.2478/amma-2025-0002

Objective: This research was designed to examine the impact of vitamin C on valproic acid-induced hepatotoxicity.
Methods: Male rabbits were separated into three groups, each with five animals. Control group: no treatment was provided. The valproic acid group received a dose of 400 mg/kg, while the valproic acid with vitamin C group received 400 mg/kg/day plus 10 mg/kg of vitamin C.
Results: The results showed the extent of the effect of valproic acid alone and with vitamin C alone on the levels of the liver enzymes AST (aspartate aminotransferase) and ALT (alanine aminotransferase) compared to the control group. The results of the AST levels showed a significant increase in the valproic acid group compared with the rest of the groups, while the group treated with vitamin C with valproic acid showed a significant decrease compared with the valproic acid group alone. Microscopic examination of liver tissue from the valproic group exhibited serious vacuolar degeneration with necrosis of hepatocytes, inflammatory cell infiltration in the portal area, recent thrombus, and congestion of the central vein. Liver samples from the valproic group displayed mild vacuolar degeneration of hepatocytes. Liver sections from the valproic + Vitamin C group showed a restoration of normal hepatocyte architecture.
Conclusion: Vitamin C can lessen the harmful oxidative effects of valproic acid in liver cells by acting as an antioxidant agent.

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Formulation and Evaluation of Valproic Acid Suppositories for Children

Tăurean Alexandrina1, Ciurba Adriana2, Todoran Nicoleta2, Cazacincu R3, Dogaru T. Maria4

1 Pharmacy no. 3, County Emergency Clinical Hospital, Tîrgu Mureş, Romania
2 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania
3 Department of Pharmaceutical Industry, Faculty of Pharmacy, ”Ovidius” University of Medicine and Pharmacy, Constanța, Romania
4 Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania

Introduction: Rectal suppositories of valproic acid were prepared using different lipophilic excipients: Suppocire NAI, Adeps solidus 50, Adeps solidus 3, Lipex 403, Cacao oleum. Each prepared suppository has been evaluated for various physical parameters like weight variation, disintegration and softening time and crushing (breaking) strength.
Methods: Suppositories were prepared by fusion method. The quantity of active drug (valproic acid) added to the suppositories was 200 mg, thus resulting 1.0 g suppositories. Prepared suppositories were visually inspected. Randomly selected suppositories were cut longitudinally and the surfaces were examined with naked eye. For determination of weight variation, 20 suppositories were weighed and the average weight was determined. Disintegration time, softening time and breaking strength of the prepared suppositories were determined according to the 5th European Pharmacopoeia.
Results: All the suppositories were free from pits, fissures and cracks. All formulas studied were disintegrated in less than 30 minutes. Valproic acid decreased the disintegration time of suppositories. The used excipient also influences the disintegration time, with a greater effect on the F1 formula (Suppocire NAI). After one month of preservation, the disintegration time of all formulas increased, but was less than 30 minutes. The softening time of the suppositories was the largest for the F1 formula (Suppocire NAI). The softening time decreases in the presence of valproic acid. The softening time and breaking strength increased for all formulas after one month.
Conclusions: The prepared suppositories were within the permissible range of physical parameters. The results obtained allow the selection of excipients in order to assure the optimum characteristics for prepared suppositories.

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Determination of Valproic Acid in Human Plasma by High-Performance Liquid Chromatography with Mass Spectrometry Detection

Vancea Szende1, Imre Silvia1, Vari C1, Dogaru Maria Titica1, Muntean Daniela-Lucia1, Căldăraru Carmen2, Dogaru G2, Donáth-Nagy Gabriella1

1 Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania
2 Faculty of Medicine, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Background: Free valproic acid is shows no characteristic absorption in the ultraviolet region (above 235 nm), therefore its direct quantification and also the quantification of the corresponding metabolites from human plasma has proven to be challenging. Aim: The aim of our study was to develop and validate an effective LC-MS method for the determination of valproic acid in human plasma without using solid phase extraction as sample preparation, with a short analysis time and high sensitivity.
Materials and methods: Valproic acid was analyzed on a reversed – phase column (Zorbax SB – C18, 100 mm x 3 mm I.D., 3.5 μm) under isocratic conditions using a mobile phase of a 40:60 (v/v) mixture of acetonitrile and 0.1% (v/v) acetic acid in water. The flow rate was 1 mL/min and the column temperature 45 ºC. In these chromatographic conditions, the retention time was 2.3 minute for valproic acid. The detection of the analyte was in single ion monitoring mode using a triple quadrupole mass spectrometer with electrospray negative ionization. The monitored ion was 143.1 m/z derived from 144.2 m/z valproic acid. The sample preparation was very simple and consisted in plasma protein precipitation from 0.2 mL plasma using 0.6 mL methanol.
Results: Calibration curves were generated over the range of 2–200 µg/mL with values for coefficient of determination greater than 0.996 and by using a weighted (1/x) quadratic regression. The values of precision and accuracy for valproic acid at quantification limit were less than 3.3% and 7.2%, for within- and between-run assays, respectively. The mean recovery of the analyte was 104%. Valproic acid samples demonstrated good short-term, post-preparative and freeze-thaw stability.
Conclusion: The method is very simple and allows obtaining a very good recovery of the analyte. The validated LC-MS/MS method could be applied to pharmacokinetics and therapeutic drug monitoring study regarding valproic acid in humans.

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