Characterization of forced degradation products of ketorolac tromethamine using LC/ESI/Q/TOF/MS/MS and in silico toxicity prediction.

Ketorolac, a nonsteroidal anti-inflammatory drug, was subjected to forced degradation studies as per International Conference on Harmonization guidelines. A simple, rapid, precise, and accurate high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (LC/ESI/Q/TOF/MS/MS) method has been developed for the identification and structural characterization of stressed degradation products of ketorolac. The drug was found to degrade in hydrolytic (acidic, basic, and neutral), photolytic (acidic, basic, and neutral solution), and thermal conditions, whereas the solid form of the drug was found to be stable under photolytic conditions. The method has shown adequate separation of ketorolac tromethamine and its degradation products on a Grace Smart C-18 (250 mm × 4.6 mm i.d., 5 µm) column using 20 mM ammonium formate (pH = 3.2): acetonitrile as a mobile phase in gradient elution mode at a flow rate of 1.0 ml/min. A total of nine degradation products were identified and characterized by LC/ESI/MS/MS. The most probable mechanisms for the formation of degradation products have been proposed on the basis of a comparison of the fragmentation of the [M + H](+) ions of ketorolac and its degradation products. In silico toxicity of the drug and degradation products was investigated by using topkat and derek softwares. The method was validated in terms of specificity, linearity, accuracy, precision, and robustness as per International Conference on Harmonization guidelines.

Identification of forced degradation products of tamsulosin using liquid chromatography/electrospray ionization tandem mass spectrometry.

A rapid and gradient 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 for the identification and structural characterization of stressed degradation products of tamsulosin. Tamsulosin, a selective α1-adrenoceptor antagonist, was subjected to forced degradation studies under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions as per ICH guidelines Q1A (R2). The drug degraded significantly under hydrolytic (base and neutral), thermal, oxidative and photolytic conditions, while it was stable to acid hydrolytic stress conditions. A total of twelve degradation products were formed and the chromatographic separation of the drug and its degradation products were achieved on a GRACE C-18 column (250mm×4.6mm, 5µm). All the degradants have been identified and characterized by LC/ESI-MS/MS and accurate mass measurements. To elucidate the structures of degradation products, fragmentation of the [M+H](+) ions of tamsulosin and its degradation products was studied by using LC-MS/MS experiments combined with accurate mass measurements. The product ions of all the protonated degradation products were compared with the product ions of protonated tamsulosin to assign most probable structures for the observed degradation products.