PDF(Pubmed)
Abstract：
OBJECTIVE: Peptides are an important class of therapeutics. Their quality is evaluated using a series of analytical tests, many of which depend on well-characterized reference standards to determine identity, purity, and strength.
OBJECTIVE: Discuss approaches to producing peptide reference standards, including vialing, lyophilization, analytical testing and stability studies.
METHODS: Case studies are used to illustrate analytical approaches to characterize reference standards, including methods for value assignment, content uniformity, and identity testing. Methods described include NMR, mass spectrometry, and chromatography techniques for identity testing and HPLC and GC methods for assessing peptide content and impurities.
RESULTS: This report describes the analytical strategy used to establish peptide reference standard and illustrates how results from multiple labs are integrated to assign a value to the final lyophilized vial. A two-step process for value assignment is described, which uses a mass balance approach to assign a quantitative value to a bulk peptide material. The bulk material is then used as a standard to assign a final value to the vialed material. Testing to confirm peptide identity and to ensure consistency of the vialed material is also described. Considerations for addressing variability, identifying outliers, and implementing stability studies are also presented.
CONCLUSIONS: The methods and case studies described provide a benchmark for best practices in establishing the preparation, analytical testing, handling, and storage of peptide reference standards for the pharmaceutical industry. Some peptide features, such as chiral or isobaric amino acids, may require additional techniques to ensure a full characterization of the peptide reference standard.
OBJECTIVE: Discuss approaches to producing peptide reference standards, including vialing, lyophilization, analytical testing and stability studies.
METHODS: Case studies are used to illustrate analytical approaches to characterize reference standards, including methods for value assignment, content uniformity, and identity testing. Methods described include NMR, mass spectrometry, and chromatography techniques for identity testing and HPLC and GC methods for assessing peptide content and impurities.
RESULTS: This report describes the analytical strategy used to establish peptide reference standard and illustrates how results from multiple labs are integrated to assign a value to the final lyophilized vial. A two-step process for value assignment is described, which uses a mass balance approach to assign a quantitative value to a bulk peptide material. The bulk material is then used as a standard to assign a final value to the vialed material. Testing to confirm peptide identity and to ensure consistency of the vialed material is also described. Considerations for addressing variability, identifying outliers, and implementing stability studies are also presented.
CONCLUSIONS: The methods and case studies described provide a benchmark for best practices in establishing the preparation, analytical testing, handling, and storage of peptide reference standards for the pharmaceutical industry. Some peptide features, such as chiral or isobaric amino acids, may require additional techniques to ensure a full characterization of the peptide reference standard.
摘要：
目的:肽是一类重要的治疗剂。使用一系列分析测试来评估它们的质量，其中许多依赖于特征明确的参考标准来确定身份，纯度,和力量。
目的：讨论生产肽参考标准的方法，包括vialing,冻干,分析测试和稳定性研究。
方法：案例研究用于说明表征参考标准的分析方法，包括值赋值的方法，含量均匀性，和身份测试。描述的方法包括NMR，质谱,以及用于身份检测的色谱技术和用于评估肽含量和杂质的HPLC和GC方法。
结果：本报告描述了用于建立肽参考标准的分析策略，并说明了如何整合多个实验室的结果以将值分配给最终的冻干小瓶。描述了值分配的两步过程，其使用质量平衡方法来将定量值分配给散装肽材料。然后将散装材料用作标准以将最终值分配给小瓶材料。还描述了确认肽同一性和确保小瓶材料的一致性的测试。解决可变性的注意事项，识别异常值，并进行了稳定性研究。
结论：所描述的方法和案例研究为建立制剂的最佳实践提供了基准，分析测试，处理,和储存用于制药行业的肽参考标准。一些肽的特征，如手性或同量异氨基酸，可能需要额外的技术来确保肽参考标准的完整表征。
目的：讨论生产肽参考标准的方法，包括vialing,冻干,分析测试和稳定性研究。
方法：案例研究用于说明表征参考标准的分析方法，包括值赋值的方法，含量均匀性，和身份测试。描述的方法包括NMR，质谱,以及用于身份检测的色谱技术和用于评估肽含量和杂质的HPLC和GC方法。
结果：本报告描述了用于建立肽参考标准的分析策略，并说明了如何整合多个实验室的结果以将值分配给最终的冻干小瓶。描述了值分配的两步过程，其使用质量平衡方法来将定量值分配给散装肽材料。然后将散装材料用作标准以将最终值分配给小瓶材料。还描述了确认肽同一性和确保小瓶材料的一致性的测试。解决可变性的注意事项，识别异常值，并进行了稳定性研究。
结论：所描述的方法和案例研究为建立制剂的最佳实践提供了基准，分析测试，处理,和储存用于制药行业的肽参考标准。一些肽的特征，如手性或同量异氨基酸，可能需要额外的技术来确保肽参考标准的完整表征。
