Study Regarding the Determination of Valproic Acid Serum Levels by Emit

Abstract

Valproic acid (n-dipropylacetic acid) is a unique anticonvulsant due to its structure, used in treating anxiety, alcoholism and mood disorders. At therapeutic doses, valproic acid half-life varies from 10 to 20 hours in adults, while it is significantly shorter (6 to 9 hours) in children. It is metabolized at hepatic level into several metabolites of which two in larger quantities, namely 2-en-VPA (2-propyl-2-pentenoic acid) and 3-keto VPA (2-propyl-3-keto-pentanoic acid) which form as a result of a beta hepatic microsomal oxidation. These two metabolites can be identified in urine in proportion of 70%. In case of an overdose or of longterm treatment, high serum levels of hepatic enzymes and hyperammonaemia may appear. A less frequent side effect is acute pancreatitis, with high serum amylase. The plasma concentration of VPA higher than 100 mg/L is concerning and a concentration higher than 450 mg/L is associated with a moderate or severe prognostic, although there is no tight correlation between plasma levels of VPA and the severity of clinical signs. Immunochemical methods use a specific antibody for the tested molecule and a marked form of the same compounds. There are two main ways to quantify the reaction: homogenous phase method and heterogeneous phase method. The homogenous methods, faster and completely automized are: EMIT (Enzyme Multiplied Immunoassay Technique) and FPIA (Fluorescence Polarization Immunoassay Technique). In the EMIT method, the marking is made through an enzyme by binding the antibody to the labelled enzyme molecule and this method can be applied confidently to determine the serum levels of valproic acid. Also, it is useful both in monitoring valproic acid treatment and, especially, in establishing a certain diagnosis in acute mono or multidrug acute intoxications. Rezumat Acidul valproic (acid n-dipropilacetic) este un anticonvulsivant unic datorită structurii sale, utilizat în tratarea anxietății, alcoolismului și tulburărilor de dispoziție. La doze terapeutice, timpul de înjumătățire al acidului valproic variază de la 10 la 20 de ore la adulți, în timp ce la copii este semnificativ mai scurt (6 până la 9 ore). Este metabolizat la nivel hepatic în mai mulți metaboliți dintre care doi în cantități mai mari, și anume 2-en-VPA (acid 2-propil-2-pentenoic) și 3-ceto VPA (acid 2-propil-3ceto-pentanoic) care se formează ca urmare a unei beta-oxidări microzomale hepatice. Acești doi metaboliți pot fi identificați în urină în proporție de 70%. În caz de supradozaj sau de tratament de lungă durată, pot apărea niveluri serice ridicate ale enzimelor hepatice și hiperamoniemie. Un efect secundar mai puțin frecvent este pancreatita acută, cu amilază serică ridicată. Concentrația plasmatică a VPA mai mare de 100 mg/L este potențial toxică, iar o concentrație mai mare de 450 mg/L este asociată cu un prognostic moderat sau sever, deși nu există o corelație strânsă între nivelurile plasmatice ale VPA și severitatea semnelor clinice. Metodele imunochimice folosesc un anticorp specific pentru molecula te...

Mini-Review on the Implications of Gene Polymorphism in the Metabolism of Xenobiotics

“…Valproic acid is metabolized at the hepatic level into several metabolites and an overdose may lead to hyperammonaemia [58].…”

A paper sensor for unbound valproic acid detection in human serum

“…17,20 The unbound serum concentration range of VPA is generally recommended to be between 2.5 and 20 mg mL À1 . Nowadays, the main detection methods for VPA include enzyme multiplied immunoassay, 21 fluorescence polarization immunoassay, 22 high-performance liquid chromatographyultraviolet detection (HPLC-UV), 23 liquid chromatographytandem mass spectrometry 24,25 and gas chromatography-mass spectroscopy (GC-MS). 26 Immunoassays are simple to perform, but their sensitivity and specificity are poor.…”