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Impurity identification and quantification for arginine vasopressin by liquid chromatography/high‐resolution mass spectrometry
Author(s) -
Wu Peize,
Ye Sijian,
Li Ming,
Li Hongmei,
Kan Ying,
Yang Zecheng
Publication year - 2020
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.8799
Subject(s) - chemistry , vasopressin , chromatography , mass spectrometry , peptide , electrospray ionization , arginine , impurity , liquid chromatography–mass spectrometry , high performance liquid chromatography , selected reaction monitoring , amino acid , tandem mass spectrometry , biochemistry , medicine , organic chemistry
Rationale 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. Methods 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. Results Under optimized experimental conditions, three deamidation products, ([Glu 4 ]AVP, [Asp 5 ]AVP, and AVP acid), two amino acid deletion impurities (des‐Pro 7 ‐AVP and des‐Gly 9 ‐AVP), one amino acid insertion impurity (endo‐Gly 10a ‐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). Conclusions This study complements the AVP impurity profile and improves the separation and discovery of other potential impurities in vasopressin analogues.