An analytical methodology with mass spectrometry as the core technique was developed for precise characterization of end groups, size, and co-monomeric composition of poly(lactic-co-glycolic acid) (PLGA) copolymers, as a preliminary step to qualify their biodegradability. Four PLGA samples were studied, with GA molar content varying from 0 to 50% and Mw ranging from 18 to 75 kg mol-1 according to the supplier. Size exclusion chromatography (SEC) and liquid state nuclear magnetic resonance (NMR) were used as either complementary or validation techniques. As confirmed by tandem mass spectrometry (MS/MS) experiments, macrocycles were most prominent in the low mass range. Nevertheless, elemental compositions derived from high resolution (HR) mass measurements of linear species were consistent with chain terminations revealed by NMR. Off-line coupling of SEC with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) permitted calibration curves to be built based on absolute molecular weights and, although slightly overestimated, so-obtained Mn and Mw values compared well with SEC and NMR results. Homogeneity of the co-monomeric content of all chains within each PLGA sample was demonstrated using surface-assisted laser desorption/ionization in a reactive mode (reactive-SALDI), a newly developed technique that takes advantage of residual acid on desorption ionization using through-hole alumina membrane (DIUTHAME) chips to induce dissociation of high-molecular-weight polymers containing cleavable C-O bonds. All HRMS data were best handled with Kendrick analysis, which helped reveal minor species and allowed automated computation of congested mass spectra.

中文翻译：

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基于质谱的生物可降解聚（乳酸-乙醇酸共聚物）共聚物全面分子表征的分析策略。

开发了一种以质谱为核心技术的分析方法，以精确表征聚乳酸-乙醇酸共聚物（PLGA）的端基，大小和共聚单体组成，以此作为鉴定其生物降解能力的第一步。根据供应商，研究了四个PLGA样品，GA摩尔含量为0至50％，Mw为18至75 kg mol-1。尺寸排阻色谱（SEC）和液态核磁共振（NMR）用作补充技术或验证技术。如串联质谱（MS / MS）实验所证实，大环化合物在低质量范围内最为突出。然而，从线性物质的高分辨率（HR）质量测量中得出的元素组成与NMR揭示的链终止一致。SEC与基质辅助激光解吸/电离质谱（MALDI-MS）的离线耦合允许基于绝对分子量建立校正曲线，尽管稍高估了，但如此获得的Mn和Mw值与SEC和NMR结果。使用反应模式下的表面辅助激光解吸/电离（reactive-SALDI）证明了每个PLGA样品中所有链的共聚单体含量的均质性，这是一项新开发的技术，利用残留酸在通过解吸电离的过程中通过孔氧化铝膜（DIUTHAME）芯片可诱导含有可裂解CO键的高分子量聚合物解离。所有HRMS数据都可以通过Kendrick分析得到最佳处理，该分析有助于揭示次要物种并允许对拥塞质谱进行自动计算。