Journal: Scientific Reports

Article Title: Tolterodine is a novel candidate for assessing CYP3A4 activity through metabolic volatiles to predict drug responses

doi: 10.1038/s41598-025-86450-9

Figure Lengend Snippet: Illustrating ( a ) the main metabolic pathways for tolterodine and ( b ) the metabolism (N-dealkylation) of tolterodine by CYP3A4 enzymes that leads to our proposed production of acetone.

Article Snippet: The non-volatile metabolite N-dealkylated tolterodine (tolterodine impurity E CRS) was obtained from LGC standards (Wesel, Germany).

Techniques:

Journal: Scientific Reports

Article Title: Tolterodine is a novel candidate for assessing CYP3A4 activity through metabolic volatiles to predict drug responses

doi: 10.1038/s41598-025-86450-9

Figure Lengend Snippet: ( a ) A chromatogram illustrating the production of two major metabolites 5-hydroxymethyl tolterodine (predominantly from the CYP2D6 isoform) and N-dealkylated tolterodine (predominantly from CYP2C9 and CYP3A4). ( b ) Biotransformation of tolterodine after 4 h incubation time with three different CYP overexpressing HepG2 cell clones and the corresponding empty vector (EV) cell clones to N-dealkylated tolterodine measured by LC-MS. *** p < 0.001 in comparison to the HepG2-CYP3A4 cells.

Article Snippet: The non-volatile metabolite N-dealkylated tolterodine (tolterodine impurity E CRS) was obtained from LGC standards (Wesel, Germany).

Techniques: Incubation, Clone Assay, Plasmid Preparation, Liquid Chromatography with Mass Spectroscopy, Comparison

Journal: Scientific Reports

Article Title: Tolterodine is a novel candidate for assessing CYP3A4 activity through metabolic volatiles to predict drug responses

doi: 10.1038/s41598-025-86450-9

Figure Lengend Snippet: ( a ) Relative cell viability of HepG2-CYP3A4 and HepG2-EV cells after exposure to different tolterodine concentrations (up to 500 µM) was evaluated by a trypan blue exclusion assay. ( b ) Production of N-dealkylated tolterodine after treatment of HepG2-CYP3A4 cells with different tolterodine concentrations. Cell supernatants were collected after 4 h treatment and measured by LC-MS.

Article Snippet: The non-volatile metabolite N-dealkylated tolterodine (tolterodine impurity E CRS) was obtained from LGC standards (Wesel, Germany).

Techniques: Trypan Blue Exclusion Assay, Liquid Chromatography with Mass Spectroscopy

Journal: Scientific Reports

Article Title: Tolterodine is a novel candidate for assessing CYP3A4 activity through metabolic volatiles to predict drug responses

doi: 10.1038/s41598-025-86450-9

Figure Lengend Snippet: Time-dependent production of N-dealkylated tolterodine and acetone by HepG2-CYP3A4 overexpressing cells after treatment with 100 µM tolterodine ( a ) over a period of 24 h in a 24-well-plate with a linear fit (R 2 = 0.9965) and ( b ) at 3 set time points in a cell culture flask. Cell supernatants and headspace were collected at given time points and measured by LC-MS and PTR-ToF-MS, respectively.

Article Snippet: The non-volatile metabolite N-dealkylated tolterodine (tolterodine impurity E CRS) was obtained from LGC standards (Wesel, Germany).

Techniques: Cell Culture, Liquid Chromatography with Mass Spectroscopy

Journal: Scientific Reports

Article Title: Tolterodine is a novel candidate for assessing CYP3A4 activity through metabolic volatiles to predict drug responses

doi: 10.1038/s41598-025-86450-9

Figure Lengend Snippet: The effect of 1 mM 1-ABT and 5 µM ketoconazole on tolterodine bioconversion in HepG2-CYP3A4 cells and empty vector (EV) reference cells regarding production of ( a ) N-dealkylated tolterodine and ( b ) acetone after treatment with 100 µM tolterodine for 4 h. Cell supernatants and headspace were collected and measured by LC-MS and PTR-ToF-MS respectively. *** p < 0.001 when compared to HepG2-CYP3A4 cells treated without inhibitor.

Article Snippet: The non-volatile metabolite N-dealkylated tolterodine (tolterodine impurity E CRS) was obtained from LGC standards (Wesel, Germany).

Techniques: Plasmid Preparation, Liquid Chromatography with Mass Spectroscopy