鲑降钙素有关物质结构HPLC MS/MS鉴定的计算机辅助方法

建立了一种辅助固相合成的鲑降钙素有关物质质谱解析的方法.根据主成分的氨基酸序列计算其肽键裂解产生的理论离子并与质谱图中的离子进行匹配，对主成分的二级质谱子离子进行归属；根据高分辨一级质谱计算有关物质的精确分子量及其元素组成，进一步计算该杂质与主成分差异片段的元素组成；推测差异片段连接于主成分不同位置的理论杂质的结构，计算该结构的杂质在质谱裂解过程中可能产生的理论碎片离子的质荷比（m/z）；将理论碎片离子与实测质谱子离子进行匹配，推测有关物质的氨基酸序列；将推测的杂质的子离子结构与主成分的对应子离子进行比较验证杂质的结构；借助ASP+HTML编程技术实现上述过程的自动化.研究结果共推断出7个鲑降钙素相关杂质的结构，包括1个降解杂质、1个乙酰化杂质、4个氨基酸重复连接杂质和1个同分异构体杂质. 

Computer-Assisted Method for HPLC MS/MS Identification of Salmon Calcitonin Related Substances

A computer assisted mass spectrometry method for salmon calcitonin related impurities was proposed. The theoretic fragments produced from the peptide bond fragmentation were calculated in accordance to the sequence of salmon calcitonin and were matched with the observed fragments. The observed mass spectrum of salmon calcitonin was assigned according to the match result. For impurity identification, the difference between the elementary compositions of the impurity and salmon calcitonin was calculated according to the high resolution pseudo-molecular ions. The theoretic fragments for each probable sequence were calculated and were matched with the observed mass spectrum. The matched result of the candidate sequence of the impurity was finally compared to the mass spectrum of salmon calcitonin to validate the structure. The procedures described were automated with ASP+HTML programming method. The sequences of seven impurities of a salmon calcitonin were identified with the method described, including 1 demoted impurity, 1 acetyl impurity, 4 aminophenol iteration impurities, and 1 isomer impurity.