Determination of Gabapentin in Plasma by Liquid Chromatography with Fluorescence Detection after Solid-Phase Extraction with a C18 Column

Gabapentin (Neurontin®), one of the relatively new antiepileptic drugs, has a novel mechanism of action that is not fully understood. Gabapentin has been shown to increase γ-aminobutyric acid concentrations in the brain of epilepsy patients (1)(2). There is an approximate linear relationship between dose and plasma concentrations. A therapeutic range of 2–20 mg/L has been commonly accepted (2), although a higher minimum concentration of 6 mg/L has also been suggested (1). Various analytical methods have been used for the determination of gabapentin in plasma, with liquid chromatography being the most commonly used approach in clinical laboratories. Gabapentin does not have a natural chromophore; therefore, it must be derivatized to be detected spectrophotometrically or fluorometrically unless detected by mass spectrometry (3). Gabapentin has been derivatized with 2,4,6-trinitrobenzenesulfonic acid for photometric detection (4)(5). Several approaches have been described for the preparation of fluorescent derivatives. Garcia et al. (6) derivatized gabapentin with fluorescamine for determination by capillary electrophoresis. However, the preparation of o-phthalaldehyde (OPA) derivatives of gabapentin has been the most popular and practical approach for liquid chromatographic determinations (7)(8)(9)(10)(11)(12).