title: Identification and characterization of stressed degradation products of metoprolol using LC/Q-TOF-ESI-MS/MS and MS(n) experiments.
abstract: 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.
authors: National Centre for Mass Spectrometry, Indian Institute of Chemical Technology, Hyderabad, 500 607, India.
authors: Roshan M
authors: RM
authors: Borkar
authors: B
authors: B
authors: Raju
authors: R
authors: R
authors: Srinivas
authors: Prashant
authors: P
authors: Patel
authors: Satheesh Kumar
authors: SK
authors: Shetty
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006868:Hydrolysis; D007477:Ions / Q000032:analysis / Q000737:chemistry; D008790:Metoprolol / Q000032:analysis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D010782:Photolysis; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007477:Ions; D008790:Metoprolol