Abstract

Poly(D,L-lactide) (PDLLA) polymer is widely used in biomedical applications. To control the degradation of PDLLA, as well as to ensure effective quality control of the polymer raw material, it is essential to have analytical methods capable of analyzing the PDLLA oligomer species content quantitatively. In this study, liquid chromatography-mass spectrometry (LC-MS) based analytical methods were developed to quantitate oligomer species from dimer to 15mer (total of 14 analytes) in the PDLLA polymer resin. Negative electrospray ionization was employed as the LC-MS interface. For the lactic acid dimer and trimer analysis, a SIELC Primesep SB column was used for high performance liquid chromatography (HPLC) separation and selected reaction monitoring (SRM) was used as the acquisition mode. For other lactic acid oligomer (4mer to 15mer) analysis, a Phenomenex Synergi™ 4 µm Polar-RP column was used, and selected ion monitoring (SIM) was used as the acquisition mode. Both columns demonstrated good tolerability for samples with high polymer content which is critical for method development. Analytical parameters such as calibration, correlation, accuracy, and precision were evaluated. Quadratic functions best described the correlation between response and concentration for each oligomer analyte. Excellent accuracy and precision were demonstrated with both methods. The methods developed in this study can be used to evaluate the impact of manufacturing process on polymers and can also be a good reference for oligomer analysis method development of similar polymers.

摘要

聚（D，L-丙交酯）（PDLLA）聚合物广泛用于生物医学应用。为了控制PDLLA的降解以及确保聚合物原料的有效质量控制，必须具有能够定量分析PDLLA低聚物种类含量的分析方法。在这项研究中，开发了基于液相色谱-质谱（LC-MS）的分析方法来定量PDLLA聚合物树脂中从二聚体到15mer（共14种分析物）的低聚物种类。负电喷雾电离用作LC-MS界面。对于乳酸二聚体和三聚体分析，将SIELC Primesep SB色谱柱用于高效液相色谱（HPLC）分离，并将选定的反应监测（SRM）用作采集模式。对于其他乳酸低聚物（4mer至15mer）分析，使用Phenomenex Synergi™4 µm Polar-RP色谱柱，并将选定的离子监测（SIM）用作采集模式。两种色谱柱都对高聚合物含量的样品表现出良好的耐受性，这对于方法开发至关重要。评估了诸如校准，相关性，准确性和精确度之类的分析参数。二次函数最能描述每种低聚物分析物的响应和浓度之间的相关性。两种方法均显示出极好的准确性和精确度。本研究开发的方法可用于评估制造工艺对聚合物的影响，也可为类似聚合物的低聚物分析方法开发提供良好的参考。两种色谱柱都对高聚合物含量的样品表现出良好的耐受性，这对于方法开发至关重要。评估了诸如校准，相关性，准确性和精确度之类的分析参数。二次函数最能描述每种低聚物分析物的响应和浓度之间的相关性。两种方法均显示出极好的准确性和精确度。本研究开发的方法可用于评估制造过程对聚合物的影响，也可为类似聚合物的低聚物分析方法开发提供良好的参考。两种色谱柱都对高聚合物含量的样品表现出良好的耐受性，这对于方法开发至关重要。评估了诸如校准，相关性，准确性和精确度之类的分析参数。二次函数最能描述每种低聚物分析物的响应和浓度之间的相关性。两种方法均显示出极好的准确性和精确度。本研究开发的方法可用于评估制造工艺对聚合物的影响，也可为类似聚合物的低聚物分析方法开发提供良好的参考。二次函数最能描述每种低聚物分析物的响应和浓度之间的相关性。两种方法均显示出极好的准确性和精确度。本研究开发的方法可用于评估制造工艺对聚合物的影响，也可为类似聚合物的低聚物分析方法开发提供良好的参考。二次函数最能描述每种低聚物分析物的响应和浓度之间的相关性。两种方法均显示出极好的准确性和精确度。本研究开发的方法可用于评估制造工艺对聚合物的影响，也可为类似聚合物的低聚物分析方法开发提供良好的参考。