Thesis is based on research of antiepileptic drugs chemic-toxic effect of valproic acid. The first attempt of comparing analysis method to isolate valproic acid from biological substances methodics applied for forensic toxicology and show it ineffectively studied condition (type of solution, pH of environment) and offered more effective method for isolation of valproic acid from tissues of internal organs, allowed to isolate upto 86% analyte. We have been studied that many factors effect (pH of environment, temperature and reaction time) the gulucuronide valproic acid's hydrolyze and identify optimal condition for find valproic acid in urine. Have been studied that high quantity of valproic acid been excreted from hydrolyzing by 2M potasium hydroxide solution at 50 degree Celsius for 20 minutes. Availability of valproic acid from hydrolysis been confirmed by chromato-mass spectrometric method. Studied many methods to separate protein from blood, suitable for HLPC analysis. Maximal availability ofvalproic acid is found when using acetonitryle as protein sedimentation. Next step of purification of plasma from lipophilic substances by hexane provide getting more pure material, suitable for use in columns. Established system immuno-hromatographic test "Cannabis" company "Sniper" having selectivity which satisfied and not provide pseudopositive result when available in the urine valproic acid and it metabolits. Established, international and local systems for screening toxic substances realizing by thin layer chromotography method to identify valproic acid is impossible. Have been offered selective system (toluene-ethanol-hexan (6:1:3) and ( 6:3:1) and reagent-appearing (1. mixture (5:1) 10 % solution cupper sulphate and 2% ammonium hydroxide .2. processed by 0,3 M cupper sulphate solution and 1% o-toluidine in acetone) suitable for identify valproic acid by thin layer chromotography method while available other drugs having acidic character (benzoic, salicylic, acethylsalicylic, mephenamic acids,indomethacine, voltaren), drug substances used in combination for treatment of epilepsy (paracetamole, phenobarbitone, barbitone, clonazepame). We recommend screening system to add non selective high sensitive reagent for identification of valproric acid by using 0,1 % solution red methyl in ethanol. Also to defined substances made of carboxilic acid by thin layer chromotography system. We have been studied condition of etherification valproic acid with the help of 3-(2?-bromacetyl)-7-methoxycumarine in availability of threeethylamine, allow to foam of 2-(7?- methoxycumarine-3?-yl)-2 oxo-ethyl ether. End product differs from valproic acid by absorbing ultraviolet-wave at 300 nm, when expose by ultraviolet light getting intensive yellowish-green fluorescence. This reagent have been used to get ethers from other drugs - made of carboxylic acid by reaction of thin layer chromotography method. Which may be used as confirmation method when availability of gas-liquid chromatography and high-pressurs liquid chromatography in the laboratory. The reaction has been established in the basis of method for identification and defination of valproic acid in the blood by reaction high-pressur liquid chromatography with spectrometric or flurometric detectors. Have been developed parameters for metrological method. Established, that conditions for identify "technical" liquids by gas-liquid chromatography method not disturbed to identify by valproic acid. Pretreatment gas-liquid chromatography method to identification and determination of valproic acid in biological material direct and pre-column reaction chromatography. On the basis of reaction formation 2-(7?- methoxycumarine-3?-yl)-2 - oxo - ethyl ether of valproic acid. Analogical ethers from other carboxylic acids, as drug substances and natural metabolises of acetic acid, not disturb to identified valproic acid. Pretreatment methods have been used to study the process of isolation of valproic acid from biological material, effect of different deproteinisation by excretingthem from blood, have been studied the condition of hydrolysis glucuronide of valproic acid indentifiying them in urine and also preserved in decomposed biological material. Established, that while preserving the period of 5 months contents of valproic acid in the biological material decrees 40 %. Have been studied chromatographic character of 2 - (7?- methoxycumarine-3?-yl)-2 oxo - ethyl ether valproic, benzoic, salicylic, acetylsalicylic, mephenamic acids, indometacine, voltarene ,and condition microclumn HLPC-analizator and shows possibility of identify valproic acid when contains above drugs. The algorithm of design of research is made for forensic toxicology, to identify and determine valproic acid in biologocal materials or liquids of human organism.
