Article Figures & Data
Figures
- Fig. 1.
Mean cumulative excretion of dose in urine and feces after a single oral dose of 400 mg [14C]BYL719 (Alpelisib) to four healthy volunteers, determined by liquid scintillation counting and 19F NMR.
- Fig. 2.
Concentrations of total DRM in individual plasma time points from a single healthy volunteer after a single oral dose of 400 mg [14C]BYL719 (Alpelisib) determined by liquid scintillation counting and 19F NMR. Integration of 19F NMR signals was performed manually.
- Fig. 3.
Reconstructed 19F NMR chromatogram showing the metabolic profile of BYL719 (Alpelisib) in (A; urine) and (B; feces). Chromatograms reconstructed from total 19F NMR quantification in individual fractions generated by time-slice fraction collection on a preparative-HPLC system. Metabolites were identified by LC-MS/MS analysis of fractions containing 19F. The percentages listed are the percentage of administered dose attributable to the components determined by 19F/14C.
- Fig. 4.
Structures of metabolites of Alpelisib (BYL719) identified in human plasma, urine, and feces. The * indicates the position of the radiolabel.
- Fig. 5.
Reconstructed 19F NMR chromatogram showing the metabolic profile of BYL719 (Alpelisib) in a plasma AUC0- to 24-hour pool of a single subject. Chromatogram reconstructed from total 19F NMR quantification in individual fractions generated by time-slice fraction collection on a preparative-HPLC system. Metabolites were identified by LC-MS/MS analysis of fractions containing 19F. The percentages listed are the percentage of total observed DRM in the sample, determined by 19F/14C.
- Fig. 6.
Chart showing the internal standard corrected 19F NMR integrals obtained from analysis of standard solutions of BYL719 (Alpelisib) and internal standard 2, spiked into urine, feces, plasma, and NMR solvents at analyte:internal standard concentrations of 100:25 and 1:2.5 µg/ml, respectively. Each sample was analyzed a total of five times by 19F NMR. Relative standard deviations from the five measurements are listed.
- Fig. 7.
Excerpt from typical one-dimensional 19F spectrum showing the signal of the internal standard Fevipiprant and of Alpelisib + metabolites. The spectrum was acquired on a 24- to 48-hour human feces extract. The major metabolites of Alpelisib were not resolved from the parent compound in the 19F NMR spectrum.
Tables
Standard ID Internal Standard 1 Internal Standard 2 Structure/chemical formula 
Name Fevipiprant 3,5-Bis(trifluoromethyl)phenol
- Data Supplement -
Figure S1. Synthetic scheme for [14C]BYL719 (Alpelisib)
Figure S2. Synthetic scheme (last 2 steps) for metabolite M4. Preceding steps are published in Furet et al, 2013.
- Data Supplement -
