Division of Chemical Metrology and Analytical Science, National Institute of Metrology, Beijing, China.
College of Chemistry, Jilin University, Changchun, China.
Rapid Commun Mass Spectrom. 2020 Jun 30;34(12):e8799. doi: 10.1002/rcm.8799.
For pharmaceutical quality control, impurities may have unexpected pharmacological or toxicological effects on quality, safety, and efficacy of drugs. Arginine vasopressin (AVP) is an important cyclic peptide drug that is mainly used for the treatment of diabetes insipidus and esophageal varices bleeding. With the advancement made in analytical techniques, liquid chromatography/high-resolution mass spectrometry (LC/HRMS) has emerged as a critical technique for the identification and quantification of structurally related peptide impurities in AVP.
An LC/HRMS/MS-based method using a quadrupole ion trap-Orbitrap mass spectrometer operated in the positive ion electrospray ionization mode was developed for the determination and quantification of structurally related peptide impurities in AVP.
Under optimized experimental conditions, three deamidation products, ([Glu ]AVP, [Asp ]AVP, and AVP acid), two amino acid deletion impurities (des-Pro -AVP and des-Gly -AVP), one amino acid insertion impurity (endo-Gly -AVP), one end chain reaction product (N-acetyl-AVP), and one AVP isomer were detected. Subsequent quantification using an external standard method estimated the total mass fraction of all structurally related peptide impurities in the AVP study material to be 30.3 mg/g with an expanded uncertainty of 3.0 mg/g (k = 2).
This study complements the AVP impurity profile and improves the separation and discovery of other potential impurities in vasopressin analogues.
对于药品质量控制，杂质可能会对药物的质量、安全性和疗效产生意想不到的药理或毒理作用。精氨酸加压素（AVP）是一种重要的环状肽类药物，主要用于治疗尿崩症和食管静脉曲张出血。随着分析技术的进步，液相色谱/高分辨率质谱（LC/HRMS）已成为鉴定和定量 AVP 中结构相关肽杂质的关键技术。
建立了一种基于 LC/HRMS/MS 的方法，采用四极离子阱-Orbitrap 质谱仪，在正离子电喷雾电离模式下操作，用于测定和定量 AVP 中的结构相关肽杂质。
在优化的实验条件下，检测到三种脱酰胺产物（[Glu]AVP、[Asp]AVP 和 AVP 酸）、两种氨基酸缺失杂质（des-Pro- AVP 和 des-Gly- AVP）、一种氨基酸插入杂质（endo-Gly- AVP）、一种末端链反应产物（N-乙酰-AVP）和一种 AVP 异构体。随后使用外标法进行定量，估计 AVP 研究材料中所有结构相关肽杂质的总质量分数为 30.3mg/g，扩展不确定度为 3.0mg/g（k=2）。
本研究补充了 AVP 的杂质概况，并提高了血管加压素类似物中其他潜在杂质的分离和发现能力。
