研究动态
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一种基于化学计量学辅助的自然DES的VA-DLLME-LC-MS/MS方法,用于生物体液/组织中Garcinol的定量测定:在药代动力学和生物分布研究中的实际应用。

Chemometric assisted natural DES based VA-DLLME-LC-MS/MS method for the quantitative determination of Garcinol in biofluids/tissues: A practical application to pharmacokinetics and biodistribution studies.

发表日期:2023 Aug 21
作者: Sujitha Matta, Murali Mohan Bhandi, Kalpana Javaji, Sunil Misra, Mohana Krishna Reddy Mudiam
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

大黄素(Garcinol,GAR)是一种从龙脑树中提取得到的多异戊烯基苯酮,传统药物中被用作抗氧化剂和抗炎药物。由于具有这些活性,它具有抗癌特性。它被视为一种下一代的表观遗传学药物。我们开发了一种基于绿色溶剂的分析方法,该方法高效、复杂且高度纯化,用于定量分析生物样品(血浆、肝脏、肾脏和脾脏)中的GAR,其提取使用了深共晶溶剂(DES)。我们合成了一系列23种DES中,发现了巴西佛手香油(Th)-萜酚(T)的2:1摩尔比具有更疏水环境和GAR与DES之间更高的相互作用效率,适用于从小鼠血浆和组织样品中更好地提取。我们使用设计实验的方法,如平衡方差设计和中心复合设计,对方法条件进行了优化。该方法的验证特性,如检出限(0.193-0.237 ng/mL)、定量限(0.644-0.697 ng/mL)、较低定量限(0.5 ng/mL)、宽线性范围(R2为0.9994-0.9997)以及不低于87%的回收率,都符合生物分析方法的接受标准。富集因子高达53-60倍,萃取效率高(89-97%)。测量不确定度估计的扩展不确定度范围为10.9%-19.0%。我们开发和验证的方法有效地应用于研究小鼠中GAR的药代动力学和分布模式。版权所有 © 2023 Elsevier B.V.。保留所有权利。
Garcinol (GAR) is a polyisoprenylated benzophenone obtained from Garcinia indica used as anti-oxidant and anti-inflammatory in traditional medicine and due to these activities, it possesses anticancer properties. It is considered to be a next generation epigenetic drug. A green solvent based analytical method which is efficient, sophisticated, and highly enriched has been developed for the quantitative analysis of GAR in biological samples (plasma, liver, kidney and spleen) with the use of deep eutectic solvent (DES) for its extraction. A series of 23 DESs were synthesized and out of which, Thymol (Th)-Terpeniol (T), 2:1 molar ratio with a more hydrophobic environment and high interaction efficiency between GAR and DES was identified for the better extraction from mice plasma and tissue samples. The Design of Experiment approaches like placket-burmann design and central composite design were used to optimize the method conditions. The method validation characteristics, such as limit of detection (0.193-0.237 ng/mL), limit of quantification (0.644-0.697 ng/mL), lower limit of quantification (0.5 ng/mL), broad range of linearity with R2 (0.9994-0.9997) with a percent recovery not less than 87% was observed, which are well within the acceptance criteria for a bioanalytical method. The enrichment factor is upto 53-60 folds, with high extraction efficiency (89-97%). The measurement uncertainty was estimated with an expanded uncertainty ranged between 10.9%-19.0%. The method developed and validated was effectively applied to examine the pharmacokinetic and biodistribution patterns for GAR in mice.Copyright © 2023 Elsevier B.V. All rights reserved.