Objective: To establish a suitable method to determine the structure and source of impurities of colistimethate sodium (CMS) for drug quality control studies. Methods: Frist-dimensional system: using Acquity UPLC® Peptide CSH C18(150 mm×2.1 mm, 1.7 μm) column, the mobile phase A was phosphate buffer (7.8 g·L-1 sodium dihydrogen phosphate, adjusted to pH 6.4 with 1 mol·L-1 sodium hydroxide)- acetonitrile (19∶1), the mobile phase B was phosphate buffer-acetonitrile (1∶1). Gradient elution was performed at a flow rate of 0.3 mL·min-1. The column temperature was 30 ℃. Second-dimensional system: the Acquity BEH C18 column (50 mm×2.1 mm, 1.7 μm) column was used with ammonium formate(A)-acetonitrile mixture as mobile phase with gradient elution. The flow rate was 0.2 mL·min-1. The column temperature was 40 ℃. The detection wave length was 210 nm. The ESI source was used in negative ion mode. Results: The 2D-LC-Q TOF MS method was used to infer the structure of the 55 impurities in CMS, and the main sources were polymyxin E1-I, polymyxin E1-7MOA, polymyxin E3 and polymyxin E6. Conclusion: The structure and source of impurities in CMS are determined by 2D-LC-Q TOF MS, and the changes in the content of impurities such as manufacturers and production processes are evaluated, which is conducive to improving the production process and controlling drug quality at the source.
LI Xuan, HUANG Min-wen, SHI Hai-wei, HU Nan, ZHOU Jie, HANG Tai-jun, YUAN Yao-zuo
. Study on composition and impurity profile of complex antibiotic colistimethate sodium and its application in quality control*[J]. Chinese Journal of Pharmaceutical Analysis, 2024
, 44(1)
: 116
-125
.
DOI: 10.16155/j.0254-1793.2024.01.12
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