A new derivatization method for the determination of valproic acid in serum using tetramethylammonium hydroxide as a catalyst

Abstract

Valproic acid (VPA) pharmacokinetics is highly variable and monitoring of blood levels is necessary to determine its appropriate dosage. This study aimed to establish and validate a novel derivatization method for the determination of VPA. The method was based on the catalytic effect of tetramethylammonium hydroxide using 2,4′‐dibromoacetophenone as a derivatization reagent. After derivatization, samples were injected into the HPLC system for analysis. The method showed a good linearity in the range of 1.0–200.7 μg mL−1, and the limit of quantification was 1 μg mL−1. All values of the accuracy and relative standard deviations were acceptable for the analyses of biological samples. The recoveries were in the range from 91.6 to 97.4% for VPA with RSD <3.9%. A novel and high conversion‐rate derivatization method has been developed and validated for the determination of VPA in human serum. It can be applied to the analysis of VPA in clinic serum samples.

A simple and rapid HPLC-UV method for the determination of valproic acid in human plasma using microwave-assisted derivatization with phenylhydrazine hydrochloride

“…As shown in Fig. 3 , the conditions that provided the most derivatized product were 450 W for an irradiation time of 50 s. The reaction time for the derivatized product using MAD in this work was shorter than that of previous reported conventional heating methods [ [23] , [24] , [25] , [26] , [27] ]. The difference is that the conventional methods heat from the core of the sample through conduction or convection.…”

“…In addition, the use of catalysts has been shown to reduce reaction temperature and heating time. To this end, VPA was successfully derivatized using 2,4′-dibromoacetophenone as the derivatizing agent and tetramethylammonium hydroxide as the catalyst by heating at 55 °C for 45 min [ 27 ]. However, during HPLC analysis, column blockage may occur because of the precipitation of inorganic catalysts in the organic phase [ 27 ].…”

“…To this end, VPA was successfully derivatized using 2,4′-dibromoacetophenone as the derivatizing agent and tetramethylammonium hydroxide as the catalyst by heating at 55 °C for 45 min [ 27 ]. However, during HPLC analysis, column blockage may occur because of the precipitation of inorganic catalysts in the organic phase [ 27 ]. Therefore, it is preferable to avoid or minimize the use of inorganic catalysts during derivatization reactions.…”

Rapid and cost‐effective LC–MS/MS method for determination of hydroxycitric acid in plasma: Application in the determination of pharmacokinetics in commercial Garcinia preparations

“…A GC–MS method for HCA measurement in human plasma has been previously reported (Loe, Bergeron, Rodriguez, & Schwarz, 2001). The described procedure used a complex sample preparation, including derivatization (Bhutani, Murugesan, Kumar, Subramanian, & Prabhakar, 2018; Mao, Zhao, Sun, Lu, & Li, 2019; Santa, 2011). This is a complex multi‐step procedure, which might affect reproducibility of the method.…”

A novel and nonderivatization method for the determination of valproic acid in human serum by two‐dimensional liquid chromatography

“…In the relevant consensus guidelines, the effective therapeutic concentration of VPA ranges from 50 to 100 μg/ml and the laboratory alert value is 120 μg/ml (Hiemke et al, 2018). The individual medication of VPA during treatment can improve the control rate of epilepsy and reduce adverse reactions (Gerstner, Bell, & Konig, 2008;Yukawa, 1996).To date, several methods for the quantification of VPA concentrations in biological fluids have been developed, such as immunoassay (Cooreman et al, 2008), liquid chromatography-mass spectrometry (LC-MS) (Gao et al, 2011;Zhao et al, 2016), high-performance liquid chromatography (HPLC) (Mao, Zhao, Sun, Lu, & Li, 2019) and gas chromatography (GC) (Shahdousti, Mohammadi, & Alizadeh, 2007). Among these methods, immunoassay is the most commonly used method in clinical laboratories, while lacking selectivity.…”