The use of UV-MS correlation for the quantification of plasma metabolites on a dual-cell linear ion trap (original) (raw)

Abstract

The quantitative assessment of metabolites in samples from development in vivo studies has become an area of increasing study with the release of guidances from regulatory bodies (MIST and M3 R2) and their subsequent interpretation and implementation. The hurdles faced in metabolite identification are joined by obtaining quantitative levels on relevant metabolites for which absolute structure may not be known and for which reference standards are not available. The challenges of matrix suppression, analyte stability, and MS detector response factor make quantitation of metabolites based on a parent drug standard almost impossible. We have applied a UV correlation to assign concentrations to metabolites identified from in vitro generated samples and used the results to quantify plasma samples on the same instrument. Initially, metabolites of dextromethorphan were generated in vitro through incubations with human liver S9 fraction (2 mg/mL). Dextromethorphan was incubated for 2 hours ...

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