Sample preparation and determination of gabapentin in venous and capillary blood using liquid chromatography-tandem mass spectrometry

An analytical method for the determination of gabapentin in serum obtained from venous blood samples has been developed using high-performance liquid chromatography (HPLC)-tandem mass spectrometry. In addition, a comparative study between capillary plasma samples and venous serum samples was carried out. This demonstrates the potential for the use of the described analytical system using very small amounts of blood. As internal standard (S)-(+)-alpha-amino-cyclohexane-propionic acid hydrate was used. Gabapentin and the internal standard are structural isomers, but have different m/z values for the fragments after collision induced dissolution. Gabapentin has 172 -->154 and 172 --> 136 transitions and amino-cyclohexane-propionic acid hydrate has a 172 --> 126 transition which can be detected in tandem MS. Analysis of gabapentin was carried out on a C8 HPLC column using an isocratic mobile phase consisting of ammonium acetate (pH 3.0; 5 mM)-methanol (96:4, v/v). The analytical method was validated for venous serum samples. Limit of detection was 1.6 ng/ml and lower limit of quantification was 7.5 ng/ml. R.S.D. values and bias values were within the range of acceptance for all concentration levels. The method developed for venous serum samples is being used in a gabapentin monitoring study using population pharmacokinetic modeling. (C) 2003 Elsevier B.V. All rights reserved.