Impurity identification and quantification for arginine vasopressin by liquid chromatography/high‐resolution mass spectrometry

Abstract

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.

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“…Whereas other studies have demonstrated that the proliferation of CFs stimulated with arginine vasopressin (AVP) is obviously increased, which through V 1A R-mediated GRK2/β-arrestin/ERK1/2 signaling ( 66 ). Simultaneously, another results suggest that silencing GRK2 could inhibit the continuous production of p-ERK1/2 induced by AVP then decreased caspase-3/7 activity and H9c2 cell survival ( 67 , 68 ). Likewise, in A7r5 cells, inhibition of GRK2 can reduce AVP-mediated sustained phosphorylation of ERK1/2 and epidermal growth factor receptor activation, cell proliferation is also inhibited ( 69 ).…”

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

“…Being able to detect the low‐level impurities helps ensure patient safety 70 . Similarly, this group performed the same type of experiments for arginine vasopressin, which is a cyclic peptide drug to treat diabetes insipidus and esophageal varices bleeding 71 …”

“…70 Similarly, this group performed the same type of experiments for arginine vasopressin, which is a cyclic peptide drug to treat diabetes insipidus and esophageal varices bleeding. 71 Brinkman et al used GC-TOF-MS and UHPLC-Q-TOF-MS to compare the excreted levels of asthma medication in exhaled breath and urine samples, respectively, in severe asthma patients. The study showed a link between systemic biomarkers of drug uptake in the urine and exhaled breath that could be replicated and validated.…”

Amidation/non‐amidation top‐down analysis of endogenous neuropeptide Y in brain tissue by nano flow liquid chromatography orbitrap Fourier transform mass spectrometry

“…We also analyzed trypsin‐digested fragments of NPY; however, the fragments including the C‐terminal ends were not detected (data no shown). The proteomics technique based on the digested short peptide search was useful for identifying the large variety proteins, 10–12 but it was not suite for distinguishing among small different modifications in long peptides. The top‐down identification method was thought to be more advantageous than the bottom‐up method based on the digested peptide search 13 .…”