项目名称： 多角度表面解吸常压化学电离源质谱对口服类抗生素缓释剂体外释放度原位检测研究

项目编号： No.21505016

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 陈荣

作者单位： 东华理工大学

项目金额： 21万元

中文摘要： 相比传统抗生素制剂，口服抗生素缓释制剂由于其便利性、给药次数少、降解程度低和患者依从性提高而在药界占据着越来越重要的地位。但该制剂释药行为的变化可能导致药物中毒、细菌抗药性或体内有效性的改变，因此有必要发展有效的体外释放度检测方法以确保缓释剂的质量，促进缓释剂的发展。本研究以先进的表面解吸常压化学电离源质谱（SDAPCI-MS）为基础，设计多角度可调质谱入口，构建SDAPCI、MS与缓释剂溶出装置的检测接口，优化接口设计，并以此接口为检测平台，建立抗生素缓释剂体外释放度质谱原位定量检测新方法。针对抗生素从缓释基质溶出过程中产生的降解，建立动力学模型校正降解造成的体外释放度曲线偏差。该方法具灵敏度高、快速和稳定性强，可实时连续监测，适用于所有抗生素缓释剂体外释放度的准确检测，为缓释剂质量控制及设计提供理论基础和实验研究平台。项目在研究方法上的探索对开展相关领域的研究具有启发和借鉴意义。

中文关键词： 多角度常压化学电离源串联质谱；口服类抗生素缓释剂；原位检测；降解纠正

英文摘要： Oral sustained-release antibiotics have become increasingly important in medicine due to their convenience, reducing the times of taking medicine, lower degradation and offering patient compliance comparing to traditional antibiotics preparations. Considering that any unanticipated change in product performance of such systems may result intoxicity, antibiotic resistance and/or change in vivo efficacy, it is essential to develop suitable in vitro release testing methods to ensure product quality and performance, and to assist in product development. This study build a novel analysis device for in vitro release with surface desorption atmospheric pressure chemical ionization(SDAPCI), mass spectrometry(MS)with adjutable inlet and dissolution device of sustained release preparations, optimize detection signal of MS, and assess in vitro drug release from sustained-release antibiotics in situ based on the built device. A kinetic model was proposed and used to correct for the drug degradation in dissolve condition to obtain the actual release profiles. The study couples high sensitivity with high speed and stability including continous measurements in real time, which is suitable for reliable detection of in vitro release for all antibiotics, offer the theory and experimental platform for all oral sustained-release antibiotics's quality control and development especially in preliminary stages. And the method seems to provide highly useful initial guidelines in the development process of relevant field.

英文关键词： multi-angle SDAPCI-MS-MS ;oral sustained-release antibiotics ;in-situ analysis;degradation correction