Ling-Fei Kong, Yu-Nan Chen, Pan Yan, Tuo Qin, Xin-Tang Wang, Rui-Qi Li, Xiao-Juan Rong, Cai Tie
State Key Laboratory of Coal Resources and Safe Mining, China University of Mining and Technology-Beijing, Ding11, Xueyuan Road, Beijing 100083, China; School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Ding11, Xueyuan Road, Beijing 100083, China.
Beijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Mar 15;1219:123651. doi: 10.1016/j.jchromb.2023.123651. Epub 2023 Feb 26.
Natural bioactive compounds (NBCs) are regarded as candidates for many medical applications widely. Due to the complicated structure and biosynthesis source, only a few NBCs were supplied with commercial isotopic labeled standards. This shortage resulted in poor quantitation reliability in bio-samples for most NBCs, considering the remarkable matrix effects. NBCs metabolism and distribution studies would be restricted consequently. Those properties played critical roles in drug discovery and development. In this study, a fast, convenient, widely adopting O/O exchange reaction was optimized for stable, available, affordable NBCs O-labeled standards preparation. With O- labeled internal standard, a UPLC-MRM-based NBCs pharmacokinetics analysis strategy was formed. Pharmacokinetics of caffeic acid with Hyssopus Cuspidatus Boriss extract (SXCF) dosed mice was carried out by established strategy. Compared with traditional external standards quantitation, adapting O-labeled internal standards, both accuracy and precision were enhanced significantly. Thus, the platform built by this work would accelerate the pharmaceutical research with NBCs, by providing a reliable, wide-adapted, affordable, isotopic internal standard-based bio-samples NBCs absolute quantitation strategy.
天然生物活性化合物（NBCs）被广泛视为多种医学应用的候选物。由于其结构复杂且生物合成来源特殊，仅有少数NBCs有商业化的同位素标记标准品供应。考虑到显著的基质效应，这种短缺导致大多数NBCs在生物样品中的定量可靠性较差。NBCs的代谢和分布研究因此会受到限制。这些特性在药物发现和开发中起着关键作用。在本研究中，一种快速、便捷、广泛应用的O/O交换反应被优化，用于制备稳定、可得、经济的NBCs O标记标准品。借助O标记内标，形成了一种基于超高效液相色谱-多反应监测（UPLC-MRM）的NBCs药代动力学分析策略。采用既定策略对给予九头狮子草提取物（SXCF）的小鼠体内咖啡酸的药代动力学进行了研究。与传统的外标定量法相比，采用O标记内标显著提高了准确性和精密度。因此，本研究构建的平台将通过提供一种可靠、广泛适用、经济且基于同位素内标的生物样品NBCs绝对定量策略，加速NBCs的药物研究。
