Related Experiment Video
Updated: Jun 5, 2025
Natural Product Discovery with LC-MS/MS Diagnostic Fragmentation Filtering: Application for Microcystin Analysis
Published on: May 31, 2019
Identification and Characterization of Acidic Degradation Products of Moxidectin Drug Substance Including Degradation
Tyler C Huang1, Ayesha Nisathar1, Frank Rinaldi1
1J-Star Research, Inc., A Porton Company, 6 Cedarbrook Drive, Cranbury Township, NJ 08512, USA.
Background:
Moxidectin is an active pharmaceutical ingredient (API) extensively used in various drug products within the pharmaceutical and animal health sectors. Despite its widespread use, the analytical methods prescribed by the United States Pharmacopeia (USP) and European Pharmacopoeia (EP, Ph. Eur.) exhibit significant limitations. These methods fail to adequately separate key impurities of (23Z)-moxidectin (EP impurity L) and 3,4-epoxy-moxidectin, potentially affecting the quality control, purity assessment, and safety of moxidectin-containing products.
Objective:
The objective was to develop and validate an alternative, improved stability-indicating high-performance liquid chromatography (HPLC) method for the identification, assay, and quantification of related substances in the moxidectin drug substance, along with the analysis of its degradation pathways.
Methods:
High-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) were employed to comprehensively examine moxidectin and its two degradation products under specified acidic conditions. The degradation products were isolated and identified using a range of analytical techniques, including HRMS, NMR, and other relevant methods.
Results:
The epoxy derivative of moxidectin (relative retention time [RRT] = 1.2) was not identified under the studied acidic degradation conditions. HRMS data indicated that the degradant at RRT = 1.2 is an isomer of moxidectin, as it exhibited an identical molecular ion. Detailed NMR studies on moxidectin and its impurity at RRT-1.2 revealed differences in carbon and proton chemical shifts at positions C-22 and C-24, strongly supporting the identification of the structure as an oxime geometric isomer of moxidectin, i.e. (23Z)-moxidectin.
Conclusions:
The findings revealed specific degradation products formed under acidic conditions, offering valuable insights into the chemical transformations of moxidectin. This information is crucial for assessing the drug's stability profile and ensuring the quality and safety of moxidectin-containing products.
Highlights:
The HPLC method developed in this study significantly improves on existing USP/EP methods with regard to a separation of key impurities of (23Z)-moxidectin and 3,4-epoxy-moxidectin, offering robust performance for routine analysis of bulk moxidectin API batches and stability samples in quality control (QC) laboratories.
More Related Videos
09:20Identification of RNA Fragments Resulting from Enzymatic Degradation using MALDI-TOF Mass Spectrometry
Published on: April 11, 2022
11:00Untargeted Metabolomics from Biological Sources Using Ultraperformance Liquid Chromatography-High Resolution Mass Spectrometry UPLC-HRMS
Published on: May 20, 2013
Related Concept Videos
01:01Mass Spectrometry: Carboxylic Acid, Ester, and Amide Fragmentation
For example,...
01:30NMR and Mass Spectroscopy of Carboxylic Acids
While α protons of carboxylic acids absorb at 2–2.5 ppm, β protons absorb further upfield.
Carboxylic acids are easily identified by dissolving them in deuterium oxide, which results in a rapid exchange of the acidic protons with deuterium. This leads to the...