Characterization of forced degradation products of ketorolac tromethamine using LC/ESI/Q/TOF/MS/MS and in silico toxicity prediction |
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| Authors: | Pradipbhai D Kalariya B Raju Roshan M Borkar Deepak Namdev S Gananadhamu Prajwal P Nandekar Abhay T Sangamwar R Srinivas |
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| Affiliation: | 1. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), , Hyderabad, 500037 AP, India;2. National Centre for Mass Spectrometry, CSIR‐Indian Institute of Chemical Technology, , Hyderabad, 500 007 AP, India;3. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), , Punjab, 160 062 India |
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| Abstract: | 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. Copyright © 2014 John Wiley & Sons, Ltd. |
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| Keywords: | ketorolac tromethamine anti‐inflammatory forced degradation LC/ESI/MS/MS accurate mass measurements degradation products in silico toxicity |
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