Simple determination of valproic acid serum concentrations using BioSPME followed by gas chromatography-mass spectrometric analysis

Valproic acid (VA) is a drug widely used on the treatment of epilepsy and bipolar affective disorders, with stablished therapeutic concentration ranges in serum. The measurement of VA serum concentrations using chromatographic methods requires a sample preparation step. In this context, this study aims to describe the development and validation of an assay for VA measurement in serum using a new microextraction strategy, known as BioSPME, followed by GC-MS analysis. The extraction procedure was very simple based on direct immersion of the BioSPME tips on acidified serum, followed by agitation and desorption in methanol. The methanolic extracts were directly injected into the chromatograph. Extraction yield was 95.6 to 101.3%. The assay was linear from 10 to 150 mg L^-1. Precision, accuracy and stability assays were acceptable according to bioanalytical validation guidelines. The method was applied to 41 clinical serum samples also tested with a previously GC-MS validated assay, which used liquid-liquid extraction as sample preparation. Measurements obtained with both methods were comparable. This study is the first description of the use of BioSPME tips for a therapeutic drug. BioSPME is a promising alternative for the preparation of biological specimens prior to the determination of therapeutic drugs by GC-MS.