Simple procedure for determination of valproic acid in dried blood spots by gas chromatography–mass spectrometry

• Valproic acid is widely used to treat epilepsy and mood disorders.
• Target through serum concentrations of valproic acid are 50–100 μg ml−1.
• Dried blood spots are a new sampling alternative for therapeutic drug monitoring of valproic acid.
• The method allowed to accurately quantify valproic acid in the range of 5–250 μg ml−1.
• Valproic acid concentrations in DBS are highly correlated to concentrations in serum.

Valproic acid (VA) is a drug widely used to treat epilepsy and bipolar disorder, at recommended serum concentrations ranging form 50 to 100 μg ml-1. A novel option for therapeutic drug monitoring that has been emerging recently its testing using dried blood spots on paper (DBS), but there are no reports of its application to assaying VA. In this study, a methodology was developed for the determination of VA in 6 mm diameter DBS, equivalent to around 12 μl of blood, using gas chromatography combined with mass spectrometry. DBS were extracted with a mixture of acetonitrile and methanol (1:3, v/v). The method is linear from 5 to 250 μg ml−1 with intra-assay and inter-assay precision of 2.67–8.15% and 2.28–3.67%, respectively. Accuracy was 102.84–104.42%. VA was stable in DBS stored at 45 °C for up to 21 days. VA concentrations in DBS correlated with concentrations assayed in serum, with r = 0.9948. Mean ratio between VA concentrations in serum and DBS in clinical samples was 1.883. Dried blood spots are a viable option for collection and transport of samples and for assaying VA in the context of therapeutic drug monitoring, especially in Developing Countries.

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