LC–ESI–MS/MS study of carvedilol and its stress degradation products

Abstract

An isocratic liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method has been developed for the separation and identification of stress degradation products (DPs) of carvedilol (CAR), a non-selective b-blocker with vasodilatory properties. CAR was subjected to hydrolytic (acidic, alkaline and neutral), oxidative, photolytic and thermal stress conditions as per ICH guidelines Q1A (R2). The drug degraded under acidic, basic and photolytic stress conditions while it was stable under neutral, thermal and oxidative stress conditions. A total of five DPs were formed which were all well resolved from the parent drug as well as from each other on an Agilent XDB C-18 column (4.6 Â 150 mm, 5 mm) using a mobile phase comprising of 20 mM ammonium acetate (pH adjusted to 6) (solvent A) and acetonitrile (solvent B) in an isocratic elution method. The structures of the degradation products were elucidated by using LC-ESI-MS/MS combined with accurate mass measurements.

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

“…The chromatographic conditions were optimized using Phenomenex C18 (250 × 4.6 mm, 5.0 μm) column with a mobile phase composed of ammonium formate buffer pH 3 (Solvent A) and acetonitrile (Solvent B) in gradient mode. The gradient programme was set as follows: (T min /% proportion of solvent B): 0-2 / 20, 2-7 /33, 7-13 /33, [13][14][15] /70, 15-18 /20 and 18-21 /20. The injection volume and detection wavelength were 10 μl and 286 nm, respectively.…”

“…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 …”

“…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. [11][12][13][14] A few analytical and bioanalytical methods have been reported in the literature for the determination of IVA. It includes estimation of IVA alone [15,16] or IVA and its metabolites [17,18] in biological matrices and in formulations.…”

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

“…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. [3][4][5][6] 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. A comparison of the product ions formed in MS/MS of the protonated drug with those of the product ions of the TPs also helps in proposing most plausible structures for the TPs, which are normally explained by appropriate mechanisms.…”