Determination of unbound valproic acid in plasma using centrifugal ultrafiltration and gas chromatography:Application in TDM.
AIM
In order to monitor the free concentration of VPA in plasma, a simple and rapid method needs to be developed.


METHODS
The free fraction of VPA in plasma was obtained by centrifugal ultrafiltration (CF-UF) devices. Cyclohexanecarboxylic acid was used as internal standard. Valproate in plasma was converted to VPA by sulphuric acid acidification, and dichloromethane was used as solvent for extraction. Nitrogen was the carrier gas, the samples were separated by capillary column, and the flame ionization detector was used to detect VPA fragment ions for quantitative analysis.


RESULTS
The assay had good specificity and stability. The linear range of the assay was 0.56-28.11 mg/L. The intra-day and inter-day precision (RSDs) of the assay were all within 15%, and the accuracy (RE) was 2.58%. The recoveries of VPA with three different concentrations were 102.03 ± 1.05, 101.45 ± 2.08 and 102.58 ± 3.38. The results of therapeutic drug monitoring (TDM) in pediatric inpatient group and outpatient group showed significant differences between the two groups (P < 0.001).


CONCLUSION
This assay has low cost and good analytical performance, so it can be developed into a routine TDM method of unbound VPA. We recommend the monitoring of unbound VPA concentration in pediatric inpatients during clinical use of VPA.
['Gu|Xurui|X|', 'Yu|Shuran|S|', 'Peng|Qilin|Q|', 'Ma|Mubai|M|', 'Hu|Yani|Y|', 'Zhou|Boting|B|']
D000293:Adolescent D002648:Child D002675:Child, Preschool D002849:Chromatography, Gas D016903:Drug Monitoring D004827:Epilepsy D005260:Female D006801:Humans D007223:Infant D008297:Male D014462:Ultrafiltration D014635:Valproic Acid
Unbound valproic acid Centrifugal ultrafiltration Gas chromatography Therapeutic drug monitoring Pediatric