Discovery of A Novel Trimebutine Metabolite and its Impact on
            <i>N</i>
            -Desmethyltrimebutine Quantification by LC–MS/MS

Glucuronides, especially acyl glucuronides, were often found to be unstable in vitro and in vivo. Acyl glucuronide metabolites can convert back to the parent drugs at physiological pH through hydrolysis. Glucuronides can also undergo in-source fragmentation during MS ionization to form the same ions as those of the parent compounds, which could cause interference to the analysis of the parent compounds. All of these may cause significant challenges in developing LC–MS/MS bioanalytical assays of labile glucuronides or parent compounds in the presence of glucuronide metabolites. In this manuscript, we will discuss these challenges and summarize recommended strategies and practices for fast and efficient method development. Critical considerations in assay development will also be discussed.

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Discovery of A Novel Trimebutine Metabolite and its Impact on N -Desmethyltrimebutine Quantification by LC–MS/MS

Abstract: An acidification step was introduced in the extraction procedure to completely hydrolyze the glucuronide and measure the total NDMT in plasma, rendering this method a successful fit-for-purpose assay.

Cited by 2 publications

References 27 publications

The Prevalence of Several Treatments in Preventing the Back Conversion of Acyl Glucuronide Metabolites in Abbreviated New Drug Applications

The Prevalence of Several Treatments in Preventing the Back Conversion of Acyl Glucuronide Metabolites in Abbreviated New Drug Applications

Challenges and Recommendations in Developing LC–MS/MS Bioanalytical Assays of Labile Glucuronides and Parent Compounds in the Presence of Glucuronide Metabolites

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