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msall strategy for comprehensive and quantitative analysis of PEG and PEGylated doxorubicin by LC-high resolution Q-Q-TOF mass spectrometry and its application to pharmacokinetics study of MPEG550-DOX,MPEG2K-DOX and MPEG10K-DOX in rats

MSALL strategy for comprehensive and quantitative analysis o...

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第三届全国药物代谢动力学青年科学家论坛暨刘昌孝人才奖颁奖大会

作者： Lei Yin Tianming Ren Shiying Zhao Jingkai Gu Research Center for Drug Metabolism School of Life ScienceJilin University Research Institute of Translational Medicine The First Hospital of Jilin University

Aim:Establish and develop an LC-Q-Q-TOF MS/MS method based on msall technique for comprehensive and quantitative analysis of PEG conjugates and released compounds in biological samples and its application to a pharmacokinetic study of MPEG550-DOX,MPEG2 K-DOX and MPEG10 K-DOX in rats..Methods:Due to the complex structure and diverse physiochemical property of PEG,quantification analysis of PEG and PEGylated molecular agents in biological matrix presented many challenges in terms of assay sensitivity,selectivity,and *** this study,a data-independent acquisition method,msall-based approach using electrospray ionization(ESI) coupled quadrupole time of flight mass spectrometry(MS),was firstly utilized for the quantitative analysis of PEGylated pharmaceuticals in complex biological *** one injection,msall technique consists of a Q1 mass window through all the precursor ions,fragmenting in Q2(collision cell) and recording precursor ions(at low CE) and product ions(at high CE) with different ***:PEGylated doxorubicin was used as a representative compound of PEGylated drugs for this *** doxorubicin underwent dissociation in the second Quadrupole to generate a series of high resolution PEG related ions at m/z 89.0611,133.0869,177.1102,221.1366,265.1622,309.1878,353.2108 of various number repeating ethylene oxide subunits and compound related ions at m/z 321.0838,361.0785,***2 K-doxorubicin specific ions(at m/z 365.0735) have the better signal to noise ratio compared with the PEG related ions,which is more applicable when the chromatographic behavior of PEG and PEGylated small molecules is *** and PEGylated small molecules were detected by positive ion electrospray ionization followed by the high resolution extracted ions based on PEG and the specific *** method was successfully applied to pharmacokinetic study of MPEG550-DOX,MPEG2 K-DOX and MPEG10 K-DOX in rats after vein intravenous injection of PE

关键词： LC-MS/MS msall Q-Q-TOF

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