Rapid and Sensitive Analysis of Valproic Acid in Human Red Blood Cell by LC-MS/MS

Abstract

E-mail: mgkim@jbctc.orgReceived October 9, 2011, Accepted February 17, 2012A sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed todetermine valproic acid in human red blood cell (RBC). It is important to measure the drug concentration ofthe RBC as well as that of the plasma because of drug partitioning for pharmacokinetic and pharmacodynamicstudy. The method was linear over the dynamic range of 1-100 µg/mL with a correlation coefficient r = 0.9997.The linearity of this method was established from 1 to 100 µg/mL for valproic acid in red blood cell withaccuracy and precision within 15% at all concentrations. The intra-run and inter-run assay accuracy andcoefficient of variations are all within 15% for all QC samples prepared in plasma and red blood humansamples. Then, valproic acid amount by protein precipitation in plasma was quantified by LC-MS/MS massspectrometry. The distribution ratio of VPA in RBC and plasma was analyzed by clinical samples. Based onmeasurement of the valproic acid in human red blood cell, this method has been applied to clinical research forstudy of distribution ratio of valproic acid in blood.Key Words : Valproic acid, LC-MS/MS, Human red blood cell, Validation, RBC partitioningIntroductionValproic acid (2-propyl pentanoic acid, VPA; Figure 1(a))is a broad-spectrum antiepileptic drug with unique anti-convulsant properties and is used in the treatment of primarygeneralized seizures, partial seizures and myoclonic seizures.