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Sci. Pharm. 2008, 76(4), 663-672; doi:10.3797/scipharm.0808-12 (registering DOI)

A New High-Throughput LC-MS/MS Assay for Therapeutic Level Monitoring of Valproic Acid in Human Plasma

1
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy Emil Isac 13, RO-400023, Cluj-Napoca, Romania
2
Department of Toxicology, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy Emil Isac 13, RO-400023, Cluj-Napoca, Romania
*
Author to whom correspondence should be addressed.
Received: 19 August 2008 / Accepted: 29 September 2008 / Published: 10 October 2008
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Abstract

A new high-throughput liquid chromatographic tandem mass spectrometric (LC-MS/MS) assay for the quantification of valproic acid in human plasma was developed and validated. The separation was performed on a Zorbax SB-C18 column under isocratic conditions using a 48:52 (v/v) mixture of acetonitrile and 0.1% (v/v) acetic acid in water at 45 °C with a flow rate of 0.8 mL/min. The detection of valproic acid was performed in SIM mode (m/z 143.1). The human plasma samples (0.2 mL) were deproteinized with methanol and aliquots of 2 μL from supernatants obtained after centrifugation were directly injected into the chromatographic system. The method shows a good linearity (r > 0.9972), precision (CV > 7.8 %) and accuracy (bias > 5.7 %) over the range of 5-200 μg/mL plasma. Lower limit of quantification (LLOQ) was 5 μg/mL and the recovery was between 98-106 %. The method is not expensive, it needs a minimum time for plasma sample preparation and has a run-time of 2.4 min for instrument analysis (retention time of valproic acid was 1.8 min). The developed and validated high-throughput method is very simple, rapid and efficient, with wide applications in clinical level monitoring, pharmacokinetics and bioequivalence studies.
Keywords: Valproic acid; LC-MS/MS; Therapeutic drug monitoring; High-throughput assay Valproic acid; LC-MS/MS; Therapeutic drug monitoring; High-throughput assay
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

VLASE, L.; POPA, D.-S.; MUNTEAN, D.; LEUCUTA, S. A New High-Throughput LC-MS/MS Assay for Therapeutic Level Monitoring of Valproic Acid in Human Plasma. Sci. Pharm. 2008, 76, 663-672.

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