Calcitonin salmon is an important peptide pharmaceutical, which is mainly used for the treatment of osteoporosis and hypercalcemia. Structurally related peptide impurities in a peptide pharmaceutical probably have side effect or even toxicity, thus needs to be carefully characterized according to pharmacopoeia. With the improvement of analytical techniques, liquid chromatography-high resolution mass spectrometry (LC-HRMS) has become a pivotal technique for the identification and quantification of structurally related peptide impurities in peptide materials. In this study, an LC-HRMS-based method has been developed for the identification and quantification of structurally related peptide impurities in calcitonin salmon material. With this method, 7 peptide impurities (> 1 mg/g) in United States Pharmacopoeia (USP) reference standard and 9 peptide impurities (> 1 mg/g) in European Pharmacopoeia (EP) reference standard were identified and accurately quantified. Besides the peptide impurities reported by USP and EP, several new impurities such as [7-Dehydroalanine] calcitonin salmon, triple-sulfate-calcitonin salmon, [26-Proline] calcitonin salmon, [14-Glutamic acid] calcitonin salmon, [20-Glutamic acid] calcitonin salmon, [26-Aspartic acid] calcitonin salmon, calcitonin salmon acid were observed in the reference standard materials studied. The total mass fractions of all structurally related peptide impurities in calcitonin salmon study materials were estimated to be 57.4 mg/g for USP and 46.3 mg/g for EP with associated expended uncertainties at a 95 % confidence level of 5.2 mg/g (k = 2) and 3.1 mg/g (k = 2), respectively.

中文翻译：

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降钙素鲑鱼的杂质鉴定和定量分析-液相色谱-高分辨率质谱。

降钙素鲑鱼是重要的多肽药物，主要用于治疗骨质疏松和高钙血症。肽药物中与结构相关的肽杂质可能具有副作用，甚至具有毒性，因此需要根据药典对其进行仔细表征。随着分析技术的改进，液相色谱-高分辨率质谱法（LC-HRMS）已成为鉴定和定量肽材料中与结构相关的肽杂质的关键技术。在这项研究中，已经开发出一种基于LC-HRMS的方法来鉴定和定量降钙素鲑鱼材料中结构相关的肽杂质。通过这种方法，可以分离出7种肽杂质（> 鉴定并准确定量了美国药典（USP）参考标准中的1 mg / g和9种肽杂质（> 1 mg / g）。除了USP和EP报告的肽杂质外，还有一些新的杂质，例如[7-脱氢丙氨酸]降钙素鲑鱼，三硫酸盐降钙素鲑鱼，[26-脯氨酸]降钙素鲑鱼，[14-谷氨酸]降钙素鲑鱼，[20-在所研究的参考标准物质中观察到了谷氨酸鲑鱼降钙素，[26-天冬氨酸]鲑鱼降钙素，鲑鱼降钙素。降钙素鲑鱼研究材料中所有结构相关肽杂质的总质量分数估计为USP为57.4 mg / g，EP为46.3 mg / g，相关不确定性在5.2 mg / g的95％置信度下（k = 2）和3.1 mg / g（k = 2），