Interference from a glucuronide metabolite in the determination of ramipril and ramiprilat in human plasma and urine by gas chromatography–mass spectrometry

Development and validation of UPLC tandem mass spectrometry assay for separation of a phase II metabolite of ramipril using actual study samples and its application to a bioequivalence study

“…There has also been reported a case of interference from an unknown metabolite using a GC-MS assay procedure for ramipril and ramiprilat from human urine and plasma. The interference from the unknown metabolite was reduced by including a washing step during SPE after extraction/ alkylation, prior to acylation (Persson et al, 2006). This phenomenon and many others like it have been listed in an excellent review article (Jemal et al, 1999).…”

Bioanalytical method development and validation using incurred samples—Simultaneous quantitation of ramipril and ramiprilat in human EDTA plasma by LC–MS/MS

“…1 for chemical structures). The metabolism also yields ramipril and ramiprilat diketopiperazine and various glucuronide metabolites [3][4]. Some of these metabolites, such as acyl and N-glucuronides, are especially labile and are subject to potential back-conversions during sample collection, storage and/or extraction, and after sample processing as well when they are co-extracted.…”

“…Some of these metabolites, such as acyl and N-glucuronides, are especially labile and are subject to potential back-conversions during sample collection, storage and/or extraction, and after sample processing as well when they are co-extracted. Though a few methods have been published either for ramipril only or for both ramipril and ramiprilat [5][6][7][8], the evaluations of metabolite back-conversion and demonstration of method reproducibility for incurred sample analysis are lacking despite the fact that the potential stability issues were noticed [4,9]. For example, Persson et al observed and identified an interfering N-glucuronide of ramipril [4].…”

“…Though a few methods have been published either for ramipril only or for both ramipril and ramiprilat [5][6][7][8], the evaluations of metabolite back-conversion and demonstration of method reproducibility for incurred sample analysis are lacking despite the fact that the potential stability issues were noticed [4,9]. For example, Persson et al observed and identified an interfering N-glucuronide of ramipril [4]. In addition, as glucuronides could easily be fragmented in-source to the respective parent compounds, chromatographic separation of the analytes from their respective glucuronides was necessary [10].…”

Liquid chromatography tandem mass spectrometry method for simultaneous determination of metoprolol tartrate and ramipril in human plasma

“…voltammetry [3], capillary electrophoresis [4], GC-MS [5], HPLC [6][7][8], LC-MS/MS [9], radioimmunoassay [10].…”