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Identification and characterization of stressed degradation products of metoprolol using LC/Q‐TOF‐ESI‐MS/MS and MS n experiments
Author(s) -
Borkar Roshan M.,
Raju B.,
Srinivas R.,
Patel Prashant,
Shetty Satheesh Kumar
Publication year - 2012
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1721
Subject(s) - chemistry , chromatography , mass spectrometry , hydrolysis , degradation (telecommunications) , fragmentation (computing) , tandem mass spectrometry , electrospray , electrospray ionization , forced degradation , metoprolol , organic chemistry , telecommunications , ammonium formate , computer science , operating system , medicine , cardiology
A rapid, specific and reliable isocratic high‐performance liquid chromatography combined with quadrupole time‐of‐flight electrospray ionization tandem mass spectrometry (LC/Q‐TOF‐ESI‐MS/MS) method has been developed and validated for the identification and characterization of stressed degradation products of metoprolol. Metoprolol, an anti‐hypertensive drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per ICH‐specified conditions. The drug showed extensive degradation under oxidative and hydrolysis (acid and base) stress conditions. However, it was stable to thermal, neutral and photolysis stress conditions. A total of 14 degradation products were observed and the chromatographic separation of the drug and its degradation products was achieved on a C 18 column (4.6 × 250 mm, 5 µm). To characterize degradation products, initially the mass spectral fragmentation pathway of the drug was established with the help of MS/MS, MS n and accurate mass measurements. Similarly, fragmentation pattern and accurate masses of the degradation products were established by subjecting them to LC‐MS/QTOF analysis. Structure elucidation of degradation products was achieved by comparing their fragmentation pattern with that of the drug. The degradation products DP 2 ( m/z 153) and DP 14 ( m/z 236) were matched with impurity B, listed in European Pharmacopoeia and British Pharmacopoeia , and impurity I, respectively. The LC‐MS method was validated with respect to specificity, linearity, accuracy and precision. Copyright © 2011 John Wiley & Sons, Ltd.