Quantification of valproic acid and its metabolite 2-propyl-4-pentenoic acid in human plasma using HPLC-MS/MS.
A specific and sensitive HPLC-MS/MS method for the quantitative determination of valproic acid (VPA) and its metabolite, 2-propyl-4-pentenoic acid in human plasma has been developed, using VPA-d15 as the internal standard. The method was based on pre-column derivatization using 4-dimethylaminobenzylamine dihydrochloride. The derivatives were separated with a gradient elution and quantified by positive electrospray ionization with multiple reaction monitoring. The assay provides routine quantification limits of 200 ng/mL for VPA and 20 ng/mL for 4-ene VPA with within- and between-day coefficients of variation of <10%. This method has been applied to the analysis of plasma samples obtained from patients treated with this drug.
Cheng
Hao
H
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, OH 43210, USA.
Liu
Zhongfa
Z
Blum
William
W
Byrd
John C
JC
Klisovic
Rebecca
R
Grever
Michael R
MR
Marcucci
Guido
G
Chan
Kenneth K
KK
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005229:Fatty Acids, Monounsaturated / Q000097:blood*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014635:Valproic Acid / Q000097:blood* / Q000493:pharmacokinetics
D005229:Fatty Acids, Monounsaturated; C045022:2-propyl-4-pentenoic acid; D014635:Valproic Acid