Development and validation of a HPLC-UV method for the quantification of antiepileptic drugs in dried plasma spots

Sara Baldelli; Dario Cattaneo; Luciana Giodini; Lorena Baietto; Giovanni Di Perri; Antonio D’Avolio; Emilio Clementi

doi:10.1515/cclm-2014-0472

Article

Development and validation of a HPLC-UV method for the quantification of antiepileptic drugs in dried plasma spots

Sara Baldelli , Dario Cattaneo , Luciana Giodini , Lorena Baietto , Giovanni Di Perri , Antonio D’Avolio and Emilio Clementi

Published/Copyright: August 12, 2014

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 53 Issue 3

Abstract

Background: Therapeutic drug monitoring (TDM) of antiepileptic drugs is widely used in clinical practice to optimise therapy, but it is limited by technical problems and cost considerations. The aim of the present study was: 1) to validate a chromatographic method for the concomitant determination of levetiracetam, lamotrigine, ethosuximide, felbamate, rufinamide, zonisamide and monohydroxycarbamazepine; 2) to develop it for dried plasma spot (DPS) assessing its reliability against the classical determination from plasma; and 3) test its clinical application.

Methods: Extraction of plasma samples and DPS was done by simple precipitation. Chromatographic analysis was performed using high performance liquid chromatography with ultraviolet detection. After validation, both methods were applied for the quantification of plasma samples from patients on antiepileptic therapy.

Results: Mean inter- and intra-day accuracy and precision were <15% for all compounds both in plasma and in DPS samples. DPS samples were considered stable under tested conditions. Measurements between plasma and DPS samples appeared related (p<0.0001). Bland-Altman analysis revealed accordance in lamotrigine values with mean overestimation of concentration for DPS sample of 2.8%. Also for monohydroxycarbamazepine data the agreement was acceptable (mean overestimation of 9.2%). For levetiracetam mean difference was 7.6%, while for ethosuximide mean percentage difference was 20.6%.

Conclusions: The developed methods simplify TDM of antiepileptic drugs. This is particularly relevant for the method on dried spot sample devices because it facilitates further sample handling, stability and shipments making the management of therapies in epileptic patients easier also in hospitals devoid of a dedicated laboratory.

Keywords: antiepileptic drugs; dried plasma spots; high performance liquid chomatography

Corresponding author: Sara Baldelli, Chem.D., Unit of Clinical Pharmacology Luigi Sacco University Hospital via GB Grassi 74, 20157 Milano, Italy, Phone: +39 0250319619, Fax: +39 0250119646, E-mail: baldelli.sara@hsacco.it

aAntonio D’Avolio and Emilio Clementi contributed equally to this work.

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Received: 2014-5-2

Accepted: 2014-7-21

Published Online: 2014-8-12

Published in Print: 2015-2-1

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Articles in the same Issue

https://doi.org/10.1515/cclm-2014-0472

Keywords for this article

antiepileptic drugs; dried plasma spots; high performance liquid chomatography