Clinical Chemistry
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Clinical Chemistry 48: 1696-1702, 2002;
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(Clinical Chemistry. 2002;48:1696-1702.)
© 2002 American Association for Clinical Chemistry, Inc.

Therapeutic Drug Monitoring of Anticonvulsant Drugs by Micellar HPLC with Direct Injection of Serum Samples

Adrián Martinavarro-Domínguez1,2, Maria-Elisa Capella-Peiró1, Mayte Gil-Agustí1, José V. Marcos-Tomás2 and Josep Esteve-Romero1a

1 Àrea de Química Analítica, Universitat Jaume I, Campus de Riu Sec, 12080 Castelló, Spain.

2 Servei d’Anàlisis Clíniques, Hospital Verge dels Llíris, 03804 Alcoi, Alacant, Spain.

aAuthor for correspondence. E-mail estevej{at}exp.uji.es.

Background: We developed a micellar liquid chromatographic (MLC) procedure for the determination of three extensively monitored antiepileptics in serum samples: carbamazepine, phenobarbital, and phenytoin.

Methods: We determined the composition of the mobile phase after modeling the elution behavior of the antiepileptics in hybrid micellar mobile phases of sodium dodecyl sulfate (SDS) with different organic modifiers (propanol, butanol, or pentanol) in an experimental design that used five mobile phases, a C18 column, and ultraviolet detection. In the micellar chromatographic system, the serum samples can be injected directly.

Results: The optimum mobile phase was 70 mL/L butanol in 0.05 mol/L SDS, pH 7, in which the three antiepileptics were resolved in <10 min. Intra- and interday precision was evaluated at four different drug concentrations within the therapeutic range (n =10); CVs were <2.1%. The method was applied to the analysis of 120 serum samples, and results were similar to those obtained by the TDx® method.

Conclusions: The MLC method allows chromatographic determination of three antiepileptics, using an interpretative strategy of optimization, without pretreatment of the serum samples and with direct injection in a hybrid micellar mobile phase of SDS–butanol. The method provides complete resolution and quantification of mixtures of two and three antiepileptics.






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Copyright © 2002 by the American Association for Clinical Chemistry.