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论文类型：期刊论文

发表时间：2019-09-01

发表刊物：JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES

收录刊物：EI、PubMed、SCIE

卷号：1125

页面范围：121716

ISSN号：1570-0232

关键字：PEG-PLA; In-source CID; LC-MS/MS; Pharmacokinetics

摘要：Poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) is a biocompatible and amphiphilic block copolymer composed of a hydrophilic PEG block and a hydrophobic PLA block, which can self-assemble into micelles in water. It is one of the most commonly used biodegradable polymers for drug encapsulation, drug solubilization and drug delivery. Due to the complexity and heterogeneity of PEG-PLA, the precise analysis of this polymer is a great challenge. This study reports an application of an UPLC tandem mass spectrometry coupled with in-source collision induced dissociation (CID) technique for the analysis of a model compound mPEG2000-PDLLA2500-COOH, which could be dissociated in source and generate a series of fragment ions corresponding to its subunits. These surrogate ions including PLA-specific and PEG-specific fragment ions could be further broken into specific product ions in collision cell. Finally, the ion transition at m/z 505.0 -> 217.0 was selected for the quantitation of mPEG2000-PDLLA2500-COOH. This assay achieved a lower limit of quantitation (LLOQ) of 0.05 mu g/mL with only 30 mu L rat plasma. The linear range is 0.05 to 5 mu g/mL. Intraday and interday accuracy and precision were within +/- 12.1%. The method was successfully applied to the pharmacokinetic study of mPEG2000-PDLLA2500-COOH in rats. The results revealed that LC-MS/MS coupled with in-source CID is a sensitive and specific strategy for analysis of PEG-PLA. This method can be potentially extended to the analysis of other pharmaceutical polymer excipients.