开发一种测定血液中舍曲林含量的方法

Anastasia S. Zhuravleva, P. S. Vikman, Evgeniya A. Gritsyuk, O. Strelova, N. A. Chuvina
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摘要

目的 开发生物液体中舍曲林的分离和测定方法。材料和方法研究使用 "左洛复 "片剂(美国辉瑞公司),使用以下设备:液相色谱仪 Shimadzu LC-20 Prominence(日本),带检测器 SPD-M20A;气相色谱仪 Agilent Technologies(美国)7890 A / 5977 MSD,(程序 MassHunter GC-MS);水域真空装置和固相萃取 Oasis HLB 滤芯;木瓜蛋白酶(MedFloran,俄罗斯);胰蛋白酶、糜蛋白酶、透明质酸酶(Lidaza)(Samson-Med LLC,俄罗斯);不同制造商生产的试纸,商品名分别为 "Be sure"、"Narco"、"Narco":"Be sure"、"NarcoCHEC"、"FACTOR-MED"。给实验动物--豚鼠服药后采集尿液样本。在 pH = 10、11 和 12(舍曲林的 pKa 值为 9.48)的条件下,用有机溶剂及其混合物进行液相色谱分析,从舍曲林盐溶液中分离出舍曲林碱基。根据 Choger 提出的方法,在富集的捐献者血液模型样本上对舍曲林的血样制备方法(液液萃取、固相萃取和酶水解)的有效性进行了研究。结果显示用免疫层析试纸对 1,4-苯并二氮杂卓衍生物和合成大麻仿生药("香料")进行尿液检测,结果呈交叉阳性。用 1 毫克/毫升的舍曲林溶液进行复查,结果为阴性。在尿液中测定了主要代谢物去甲舍曲林,其峰值保留时间约为 12.75 分钟,原始物质和舍曲林合成过程中的峰值为舍曲林亚胺,原始舍曲林的峰值保留时间约为 12.65 分钟。已开发出一种用高效液相色谱法检测舍曲林的方法。结论使用胰蛋白酶对血液进行酶水解的技术可使萃取率比氯仿液-液萃取提高 1.5 倍,比固相萃取提高 2 倍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DEVELOPMENT OF A METHOD FOR DETERMINING SERTRALINE IN THE BLOOD
Aim Development of methods for isolation and determination of sertraline in biological fluids. Materials and methods. The study was conducted with tablettes "Zoloft" ("Pfizer", USA) using the following equipment: liquid chromatograph Shimadzu LC-20 Prominence (Japan) with detector SPD-M20A, gas chromatograph Agilent Technologies (USA) 7890 A / 5977 MSD, (program MassHunter GC-MS ), waters vacuum unit and cartridges for solid-phase extraction Oasis HLB; papain enzymes (MedFloran, Russia); trypsin, chymotrypsin, hyaluronidase (Lidaza) (Samson-Med LLC, Russia); test strips from different manufacturers under trade names: "Be sure", "NarcoCHEC", "FACTOR-MED". Urine samples were obtained after administration of the drug to laboratory animals - guinea pigs. Isolation of the base of sertraline from a solution of its salt was carried out by LLE with organic solvents and their mixtures at pH = 10, 11 and 12 (pKa sertraline 9.48). Obtaining data on the effectiveness of blood sample preparation methods (liquid-liquid extraction, solid-phase extraction and enzymatic hydrolysis) for sertraline was carried out on enriched model samples of donor blood according to the method proposed by Choger. Results. Cross-positive urine test results were obtained with immunochromatographic test strips for derivatives of e 1,4-benzodiazepine and synthetic cannabimimetics ("spice"). And a follow-up with 1 mg / ml solution of sertraline gave a negative result. Desmethylsertraline, a major metabolite, was determined in the urine, a peak with a retention time of about 12.75 min, the peak of the original substancesand during the synthesis of sertraline - sertralinimine and the peak of the native sertraline and with a retention time of about 12.65 minutes. A method for detecting sertraline by HPLC has been developed. Conclusion. The use of the technique of enzymatic hydrolysis of blood with trypsin allows to increase the degree of extraction by 1.5 times compared with liquid-liquid extraction with chloroform and by 2 times compared with solid-phase extraction.
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