Identification and characterization of stressed degradation products of metoprolol using LC/Q‐TOF‐ESI‐MS/MS and MSⁿ 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.

Characterization of degradation products of Ivabradine by LC‐HR‐MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H2SO4 acid hydrolysis

“…Over the years hyphenated techniques have been increasingly used for structural characterization of degradation products of drugs and impurities against the time consuming process involved in preparative isolation of degradation products followed by spectral characterization …”

Liquid chromatography/electrospray ionization tandem mass spectrometry study of repaglinide and its forced degradation products

“…Characterization of DPs and understanding of the degradation pathways are very crucial for safety and potency assessment of the drugs in clinical trials. Over the last decade, liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS) in combination with accurate mass measurement has been increasingly used for the structural characterization of DPs of drugs formed under various stress conditions . For example, Shah et al have reported a study on complete degradation behavior and the identification of stressed DPs of atorvastatin using LC/MS/MS and MS n experiments .…”

“…Jain and Basniwal have reviewed the analytical techniques that are used for characterization and quantification of thresholds of impurities and DPs in various matrices . Recently, we have demonstrated the applications of LC/MS/MS, MS n experiments and accurate mass measurements for the identification and structural characterization of stressed DPs of various active pharmaceutical drugs like prulifloxacin, metoprolol, milnacipran and carvedilol . The information from the structural characterization of DPs is expected to be useful to develop new drugs with improved stability.…”

Characterization of forced degradation products of pazopanib hydrochloride by UHPLC‐Q‐TOF/MS and in silico toxicity prediction

“…Over the years, hyphenated techniques such as GC‐MS and liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) have been increasingly used for structural characterization of transformation products of drugs and impurities against the time consuming process involving preparative isolation of transformation products followed by spectral characterization . The analysis involves high performance liquid chromatography/ultra high performance liquid chromatography (HPLC/UHPLC) method development for the separation of TPs from the drug followed by structural characterization of the TPs using LC‐MS/MS in combination with elemental compositions of ions derived from their accurate masses.…”