Development of Method for Determining Topiramate in Various Biological Matrices (Plasma, Saliva, Hair) and Its Application in Clinical Practice

Abstract

The aim of this work was to develop and validate of method for the determination of topiramate (TPM) by a high-performance liquid chromatographic method coupled to triple-quadrupole mass spectrometry (LC-MS/MS) in MRM mode in the human plasma, saliva, and hair, and implementation of this method for the determination of TPM in patients with epilepsy. Saliva may as an alternative matrix for monitoring drug level, and hair drug content may be a reliable biomarker of the history of drug exposure, allowing to assess patient long-term compliance. Chromatographic separation was achieved in 3 min on a Kinetex analytical column (5 μm C18 100 Å, 100×2.1 mm) using an isocratic elution of acetonitrile and 10 mM ammonium acetate at a ratio of 80:20 (v/v) and a flow rate of 0.2 mL/min. Detection of TPM and internal standard (IS) (TPM-d12) was performed in negative ion mode (ESI−). The following transitions were used m/z 338 → 77.90; 338 → 95.90 for TPM and 350.3 → 78.20 for IS. The method showed to be selective, accurate, precise, and linear for TPM over the concentration ranges of 0.20-30 μg/mL (plasma, saliva), and 5.0-500.0 ng/mL (hair). The simple and robust LC-MS/MS method was successfully applied for the determination of TPM in patients with epilepsy.

Keywords

• plasma
• saliva
• lc-ms/ms
• hair
• topiramate