Laboratory toxicological diagnosis of trazodone intoxications

S. A. Karpushyna, S. V. Baiurka, S. Merzlikin
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Abstract

When determining the cause of poisoning by antidepressant drugs, the data of laboratory toxicological studies of biofluids for the presence of this group of drugs are of key importance. Aim. To develop the methods for determining the antidepressant drug trazodone in the blood and urine samples using high-performance liquid chromatography with a UV spectrophotometric detection, which is suitable for analytical diagnosis of the thymoleptics intoxications. Materials and methods. The model samples of human biofluids spiked with trazodone were studied. The antidepressant was isolated from the blood and urine by the liquid-liquid extraction with methylene chloride from the alkaline medium at pH 9. Concomitant endogenous impurities were removed by extraction with diethyl ether from the acidic medium at pH 1. In the study of the blood the erythrocyte mass was pre-precipitated with the help of 10 % of trichloroacetic acid solution. Chromatographic analysis was performed on a microcolumn chromatograph using a column with a reversed-phase of C18. Results. The absolute retention time of trazodone in extracts from the model samples of biofluids was 17.91±0.09 min. The quantitative content of trazodone was determined at 250 nm by the calibration dependence of the chromatographic peak area on the concentration (μg/ml) y=(1.74∙10-3±1∙10-5)x. Under the indicated extraction conditions, 35±4 % and 78±4 % of trazodone were isolated from the blood and urine, respectively. Conclusions. The methods of trazodone isolation from the biofliuds by liquid extraction followed by the determination of the drug by high performance liquid chromatography with a multiwave UV spectrophotometric detection have been developed. The methods are recommended for using in the practice of forensic and clinical toxicology.
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曲唑酮中毒的实验室毒理学诊断
在确定抗抑郁药物中毒的原因时,生物体液中该类药物的实验室毒理学研究数据是至关重要的。建立高效液相色谱-紫外分光光度法测定血液和尿液中抗抑郁药物曲唑酮的方法,使之适用于胸腺中毒的分析诊断。材料和方法。研究了加入曲唑酮的人体生物体液模型样品。在pH为9的碱性培养基中,采用二氯甲烷液液萃取法从血液和尿液中分离出抗抑郁药。在pH为1的酸性培养基中,用乙醚萃取去除伴随的内源性杂质。在血液研究中,红细胞团在10%的三氯乙酸溶液的帮助下进行预沉淀。色谱分析在微柱色谱仪上进行,色谱柱为c18反相。生物液模型样品提取液中曲唑酮的绝对保留时间为17.91±0.09 min。通过色谱峰面积对浓度(μg/ml) y=(1.74∙10-3±1∙10-5)x的定标依赖性,在250 nm处测定曲唑酮的定量含量。在规定的提取条件下,血液和尿液中曲唑酮的提取率分别为35±4%和78±4%。建立了从生物液中提取曲唑酮,然后用高效液相色谱-多波紫外分光光度法测定药物含量的方法。建议在法医和临床毒理学实践中使用这些方法。
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