地塞米松在生物组织中的检测方法及其在药物局部动力学评价中的应用

Q3 Pharmacology, Toxicology and Pharmaceutics
Dina V. Yunina, Valentin P. Ageev, Andrey V. Zaborovskiy, Larisa A. Tararina, Sergei V. Tsaregorodtsev, Alexander V. Kokorev, Dmitry N. Andreev, Aleksandra E. Pyanzina, Vasilisa I. Shlyapkina, Nikolay A. Pyataev, Oleg A. Kulikov
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引用次数: 0

摘要

糖皮质激素的药代动力学研究往往需要解决药理学的基础和应用任务。基于紫外检测的高效液相色谱方法因其可用性而具有吸引力,但其灵敏度较低,不足以研究体内动力学。在本研究中,我们提出了一种测定生物物体中地塞米松的方法,该方法基于使用高效液相色谱和紫外检测,并且具有足够的灵敏度来测定生物介质(血液和关节周围组织)中的药物。材料与方法:以阿替洛尔为内标,在酸性介质中丙酮液液萃取地塞米松。分析在Kromasil-100 C18色谱柱上进行。流动相为甲醇与磷酸盐缓冲液的混合物,pH=5.6,比例为50÷50。探测器-紫外,波长- 254纳米。该方法的定量限为50 ng/mL;校正曲线在50 ~ 1000 ng/mL浓度范围内呈线性关系。采用该方法对自身免疫性关节炎模型大鼠滑膜周围组织进行检测。结果:本研究表明,与水溶性地塞米松相比,脂质体形式的地塞米松关节内注射可以使产品的活性浓度在关节和关节周围组织中保持更长的时间,这为提高其治疗效果创造了先决条件。结论:本方法为血液和关节周围组织等生物样品中地塞米松的检测提供了一种灵敏、特异的方法。初步研究结果表明,脂质体形式的地塞米松可能比水溶性形式表现出更好的药代动力学特性,这可能导致改善的治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Method of detection of dexamethasone in biological tissues and its application to assess the local kinetics of this drug
Introduction: The study of the pharmacokinetics of glucocorticosteroids is often required to solve fundamental and applied tasks of pharmacology. HPLC methods based on ultraviolet detection are attractive due to their availability, but their sensitivity is low enough to study in vivo kinetics. In this study, we propose a method for the determination of dexamethasone in biological objects, based on the use of HPLC with UV detection and having sufficient sensitivity to determine the drug in biological media (blood and periarticular tissues). Materials and methods: Extraction of dexamethasone from biosamples was carried out by liquid-liquid extraction with acetone in an acidic medium using atenolol as an internal standard. The analysis was carried out on a Kromasil-100 C18 column. A mixture of methanol with phosphate buffer in the ratio 50÷50, pH=5.6 was used as the mobile phase. Detector - UV, wavelength - 254 nm. The LLOQ of the method was 50 ng/mL; the calibration curve demonstrated linearity in the con-centration range of 50-1000 ng/mL.The method was used to detect the medicinal product in peri-synovial tissues of rats with an autoimmune arthritis model. Results: This study demonstrated that intraarticular injection of the liposomal form of dexamethasone, compared with its water-soluble form, allows maintaining the active concentration of the product in the joint and periarticular tissues for a longer time, which creates prerequisites for enhancing its therapeutic effect. Conclusion: The proposed method provides a sensitive and specific approach for measuring dexamethasone in biological samples, such as blood and periarticular tissues. Preliminary findings indicate that the liposomal form of dexamethasone may exhibit better pharmacokinetic properties than the water-soluble form, which could lead to improved therapeutic outcomes.
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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