Figures S1a-S8d: Mass spectral and NMR spectral data for ramelteon metabolites

Supplemental Information for: METABOLISM OF RAMELTEON IN HUMAN LIVER MICROSOMES AND CORRELATION WITH THE EFFECT OF FLUVOXAMINE ON RAMELTEON PHARMACOKINETICSby R. Scott Obach and Tim F. RyderDrug Metabolism and Disposition Figures S1a-S8d: Mass spectral and NMR spectral data for ramelteon metabolites

Figure S-1a; Ramelteon MS1 MS2 dau 260 MS3 dau 204

Figure S-1b Ramelteon NMR Assignments COSY: Black Arrows HMBC: Red Arrows

Figure S-1c 1H NMR Spectrum of Ramelteon

Figure S-1d COSY NMR Spectrum of Ramelteon

Figure S-1e HSQC NMR Spectrum of Ramelteon

Figure S-1f HMBC NMR Spectrum of Ramelteon

Figure S-2a; Metabolite A MS1 MS2 dau 276 MS3 dau 258 MS4 dau 159

Figure S-2b; Metabolite A COSY: Black Arrows

Figure S-2c; Metabolite A 1H NMR Spectrum

Figure S-2d; Metabolite A COSY NMR Spectrum

Figure S-2e; Metabolite A HSQC NMR Spectrum

Figure S-3a; Metabolite B MS1 MS2 dau 258 MS3 dau 202

Figure S-3b; Metabolite B COSY: Black Arrows

Figure S-3c; Metabolite B 1H NMR Spectrum

Figure S-3d; Metabolite B 1H NMR Spectrum Showing Diastereomeric Mixture Hydroxyl Proton 1 Hydroxyl Proton 2 Extra coupling of the aromatic doublets Methine

Figure S-3e; Metabolite B COSY NMR Spectrum

Figure S-3f; Metabolite B HSQC NMR Spectrum

Figure S-4a; Metabolite C MS1 MS2 dau 258 MS3 dau 202

Figure S-4b; Metabolite C COSY: Black Arrows

Figure S-4c; Metabolite C 1H NMR Spectrum

Figure S-4d; Metabolite C COSY NMR Spectrum

Figure S-4e; Metabolite C HSQC NMR Spectrum

Figure S-5a; Metabolite D MS1 MS2 dau 276 MS3 dau 185

Figure S-5b; Metabolite D COSY: Black Arrows

Figure S-5c; Metabolite D 1H NMR Spectrum

Figure S-5d; Metabolite D 1H NMR Spectrum Showing the Ratio of Regioisomers New Aromatic Singlet Together integrate to about 1

Figure S-5e; Metabolite D COSY NMR Spectrum

Figure S-6a; Metabolites E and F MS1 MS2 dau 258 MS3 dau 159

Figure S-6b; Metabolites E and F COSY: Black Arrows

Figure S-6c; Metabolites E and F 1H NMR Spectrum

Figure S-6d; Metabolites E and F 1H NMR Spectrum Shows Diastereomeric Mixture Hydroxyl Proton 1 Hydroxyl Proton 2 Methine 1 Methine 2

Figure S-6f; Metabolites E and F COSY NMR Spectrum

Figure S-7a; Metabolite G MS1 MS2 dau 258 MS3 dau 185

Figure S-7b; Metabolite G COSY: Black Arrows

Figure S-7c; Metabolite G 1H NMR Spectrum

Figure S-7d; Metabolite G COSY NMR Spectrum

Figure S-7e; Metabolite G HSQC NMR Spectrum No Methine

Figure S-8a; Metabolite H MS1 MS2 dau 274 MS3 dau 256

Figure S-8b; Metabolite H COSY: Black Arrows

Figure S-8c; Metabolite H 1H NMR Spectrum

Figure S-8d; Metabolite H COSY NMR Spectrum

Figures S1a-S8d: Mass spectral and NMR spectral data for ramelteon metabolites