Determination of New 4-Aryl-pyrido[1,2-c]pyrimidine Derivatives, Potential Antidepressant Agents with a High Affinity to 5-Hydroxytryptamin 1A Receptor and Serotonin Transporter Protein Receptor, with Capillary Electrophoresis

IF 1.2 4区 化学 Q4 BIOCHEMICAL RESEARCH METHODS Chromatographia Pub Date : 2023-12-04 DOI:10.1007/s10337-023-04300-0
Błażej Grodner, Marek Król, Grzegorz Ślifirski, Piotr Ślifirski, Franciszek Herold
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Abstract

A novel capillary electrophoresis method was developed for the determination of new 4-aryl-pyrido[1,2-c]pyrimidine derivatives, potential antidepressant agents, in serum. The derivatives have conformationally restricted tryptamine moiety in pharmacophore portion and exhibit high affinity to molecular targets: 5-HT1A receptor and serotonin transporter protein. The separation process was conducted using an eCAP fused-silica capillary, detection wavelength 214 nm, 200 mM phosphate buffer adjusted to pH = 8.0, temperature 20 °C, voltage 5 kV. The proposed method was validated by determining its linearity in the concentration range of 200–1000 ng/mL. A satisfactory linearity was obtained for the method, with R2 from 0.9978 to 0.9999 for all five derivatives and a limit of quantification level from 287.1 to 310.1 ng/mL. The recoveries for all derivatives were in the range from 94.7 to 100%. The speed of obtaining the result of the analysis was only 3 min. The developed method allows to determine all five derivatives both in water solutions and serum.

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新4-芳基吡啶[1,2-c]嘧啶衍生物与5-羟色胺1A受体和5-羟色胺转运蛋白受体高亲和力的潜在抗抑郁药物的毛细管电泳测定
建立了毛细管电泳测定血清中新型4-芳基吡啶[1,2-c]嘧啶衍生物的方法。该衍生物在药效团部分具有构象限制性的色胺部分,对5-HT1A受体和5-羟色胺转运蛋白具有高亲和力。分离过程采用eCAP熔融硅胶毛细管,检测波长214 nm, 200 mM磷酸盐缓冲液调节至pH = 8.0,温度20℃,电压5 kV。在200 ~ 1000 ng/mL的浓度范围内,对该方法进行了线性检验。5种衍生物的线性关系良好,R2为0.9978 ~ 0.9999,定量限为287.1 ~ 310.1 ng/mL。所有衍生品的回收率在94.7 - 100%之间。获得分析结果的速度仅为3分钟。所开发的方法允许在水溶液和血清中测定所有五种衍生物。
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来源期刊
Chromatographia
Chromatographia 化学-分析化学
CiteScore
3.40
自引率
5.90%
发文量
103
审稿时长
2.2 months
期刊介绍: Separation sciences, in all their various forms such as chromatography, field-flow fractionation, and electrophoresis, provide some of the most powerful techniques in analytical chemistry and are applied within a number of important application areas, including archaeology, biotechnology, clinical, environmental, food, medical, petroleum, pharmaceutical, polymer and biopolymer research. Beyond serving analytical purposes, separation techniques are also used for preparative and process-scale applications. The scope and power of separation sciences is significantly extended by combination with spectroscopic detection methods (e.g., laser-based approaches, nuclear-magnetic resonance, Raman, chemiluminescence) and particularly, mass spectrometry, to create hyphenated techniques. In addition to exciting new developments in chromatography, such as ultra high-pressure systems, multidimensional separations, and high-temperature approaches, there have also been great advances in hybrid methods combining chromatography and electro-based separations, especially on the micro- and nanoscale. Integrated biological procedures (e.g., enzymatic, immunological, receptor-based assays) can also be part of the overall analytical process.
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