Simple procedure for determination of valproic acid in dried blood spots by gas chromatography-mass spectrometry.
Valproic acid (VA) is a drug widely used to treat epilepsy and bipolar disorder, at recommended serum concentrations ranging form 50 to 100μg 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 6mm diameter DBS, equivalent to around 12μl 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 250μgml(-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.
Instituto de Ciências da Saúde, Universidade Feevale, Rodovia RS 239, n. 2755, Novo Hamburgo, RS CEP 93352-000, Brazil.
Liliane
L
Rhoden
Instituto de Ciências da Saúde, Universidade Feevale, Rodovia RS 239, n. 2755, Novo Hamburgo, RS CEP 93352-000, Brazil.
Marina Venzon
MV
Antunes
Instituto de Ciências da Saúde, Universidade Feevale, Rodovia RS 239, n. 2755, Novo Hamburgo, RS CEP 93352-000, Brazil.
Paulina
P
Hidalgo
Instituto de Ciências da Saúde, Universidade Feevale, Rodovia RS 239, n. 2755, Novo Hamburgo, RS CEP 93352-000, Brazil.
Cleber
C
Álvares da Silva
Instituto de Ciências da Saúde, Universidade Feevale, Rodovia RS 239, n. 2755, Novo Hamburgo, RS CEP 93352-000, Brazil. Electronic address: rafael.linden@feevale.br.
Rafael
R
Linden
D000927:Anticonvulsants / Q000097:blood*; D003906:Developing Countries; D059788:Dried Blood Spot Testing / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results; D014635:Valproic Acid / Q000097:blood*
D000927:Anticonvulsants; D014635:Valproic Acid
Dried blood spots; Gas chromatography-mass spectrometry; Therapeutic drug monitoring; Valproic acid