Identification and structural characterization of in vivo metabolites of ketorolac using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) |
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Authors: | B Raju M Ramesh Roshan M Borkar Raju Padiya Sanjay K Banerjee R Srinivas |
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Institution: | National Centre for Mass Spectrometry, Indian Institute of Chemical Technology, Hyderabad, 500 007, India. |
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Abstract: | In vivo metabolites of ketorolac (KTC) have been identified and characterized by using liquid chromatography positive ion electrospray ionization high resolution tandem mass spectrometry (LC/ESI-HR-MS/MS) in combination with online hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, blood urine and feces samples were collected after oral administration of KTC to Sprague-Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation and freeze liquid separation followed by solid-phase extraction and then subjected to LC/HR-MS/MS analysis. A total of 12 metabolites have been identified in urine samples including hydroxy and glucuronide metabolites, which are also observed in plasma samples. In feces, only O-sulfate metabolite and unchanged KTC are observed. The structures of metabolites were elucidated using LC-MS/MS and MS(n) experiments combined with accurate mass measurements. Online HDX experiments have been used to support the structural characterization of drug metabolites. The main phase I metabolites of KTC are hydroxylated and decarbonylated metabolites, which undergo subsequent phase II glucuronidation pathways. |
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