Systematical Characterization of Impurity Profiles in Daptomycin Raw Material by 2-Dimentional HPLC Tandem with MS Detector
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Published:2021-05-26
Issue:7
Volume:17
Page:908-918
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ISSN:1573-4129
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Container-title:Current Pharmaceutical Analysis
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language:en
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Short-container-title:CPA
Author:
Li Jin1,
Yao Shang-Chen1,
Yin Li-Hui1,
Hu Chang-Qin1,
Xu Ming-Zhe1
Affiliation:
1. National Institutes for Food and Drug Control, Beijing, China
Abstract
Objective:
To systematically characterize the impurity profile in Daptomycin raw material by 2 Dimensional
LC/MSn.
Method:
The target impurity was separated by first Dimensional HPLC and enriched by a 500μl loop, then desalted using
the on-line second Dimensional HPLC and analyzed by MS detector in positive mode. Their structures were characterized
based on the degradation mechanism and mass fragmentation regularity of the cyclic lipopeptide, as well as the molecular
thermodynamic calculation.
Results:
A total of 12 impurities were characterized in the raw material, including 6 degradation products;
8 impurities are reported for the first time. The mass fragmentation regularities of 2 β-isomers of
Asp residue were summarized.
Conclusion:
The structures of impurities in Daptomycin raw material, especially for β-isomer impurities, could be rapidly
identified by on-line 2 Dimensional LC/MSn method together with the molecular thermodynamic calculation.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science,Molecular Medicine,Biochemistry,Biophysics