Rapid communications in mass spectrometry : RCM · 2026
Identification and Quantification of Structurally Related Peptide Impurity in Linaclotide by Liquid Chromatography-High Resolution Mass Spectrometry.
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Cheng Jinlan, Zhang Tianji, Cui Xinling, Wu Peize, Li Ming, Hu Wenrui, Dai Xueting, Feng Xuesong
Аннотация
RATIONALE: Linaclotide is an important peptide drug used to treat irritable bowel syndrome with constipation (IBS-C). However, structurally related impurities in peptide drugs can be generated during synthesis, storage, or transport, which compromise the quality and safety. Therefore, developing a highly sensitive analytical method for impurity detection is of great significance.
METHODS: A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed. Linaclotide samples were directly analyzed using an Orbitrap mass spectrometer with an electrospray ionization (ESI) source operated in positive ion mode. Tandem mass spectrometry with collision-induced dissociation was utilized. The method leveraged high mass accuracy to identify and quantify structurally related peptide impurities in linaclotide samples from different manufacturers.
RESULTS: The method was applied to characterize the peptide impurities in linaclotide study materials. In manufacturer A's material, [Des-Tyr14]-linaclotide was found at 0.453 mg/g. The same impurity was found in manufacturer B's material at 0.768 mg/g, as well as another impurity [endo-Ala9]-linaclotide at 0.555 mg/g.
CONCLUSIONS: The developed LC-HRMS method successfully addresses the challenge of determining structurally related peptide impurities in linaclotide. Its ability to characterize specific impurities provides a valuable complement to existing quality control strategies for peptide therapeutics.
METHODS: A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed. Linaclotide samples were directly analyzed using an Orbitrap mass spectrometer with an electrospray ionization (ESI) source operated in positive ion mode. Tandem mass spectrometry with collision-induced dissociation was utilized. The method leveraged high mass accuracy to identify and quantify structurally related peptide impurities in linaclotide samples from different manufacturers.
RESULTS: The method was applied to characterize the peptide impurities in linaclotide study materials. In manufacturer A's material, [Des-Tyr14]-linaclotide was found at 0.453 mg/g. The same impurity was found in manufacturer B's material at 0.768 mg/g, as well as another impurity [endo-Ala9]-linaclotide at 0.555 mg/g.
CONCLUSIONS: The developed LC-HRMS method successfully addresses the challenge of determining structurally related peptide impurities in linaclotide. Its ability to characterize specific impurities provides a valuable complement to existing quality control strategies for peptide therapeutics.