LC, LC–MS/TOF, AND MS^N STUDIES FOR THE SEPARATION, IDENTIFICATION, AND CHARACTERIZATION OF DEGRADATION PRODUCTS OF LINEZOLID

Abstract

A comprehensive mass fragmentation of linezolid, which was not been reported so far, was established by subjecting the drug to liquid chromatography/mass spectrometric (LC-MS) analysis and multi-stage mass spectrometric studies. The objective of the present investigation was to separate, identify, and characterize all the degradation products (DPs) of linezolid, generated under various stress conditions. The drug was subjected to hydrolytic, oxidative, photolytic, and thermal stress as per International Conference on Harmonization (ICH) guideline Q1A(R2). The drug was found to be labile under acidic, basic, neutral, and oxidative stress while it was stable in photolytic and thermal stress conditions. A total of three degradation products were formed, which were separated on a C-18 column employing a gradient high-performance liquid chromatographic (HPLC) method. A complete mass fragmentation pathway of the drug was first established with the help of multi-stage (MSⁿ) and MS/TOF accurate mass studies. Then, stressed samples were subjected to LC–MS/TOF studies, which provided their fragmentation pattern and accurate masses. The mass spectral data were employed to characterize the DPs and assign structures to them. The total information was also used to establish thedegradation pathway of the drug.

Keywords:

• characterization
• forced degradation
• LC
• LC-MS/TOF
• linezolid
• MSⁿ

ACKNOWLEDGMENTS

The authors wish to extend their thanks to Prof. Saranjit Singh, Dean and Head, Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar Mohali, Punjab, India, for extending facilities and helpful discussions.