Omatograms, only metabolite total metabolite peak area are labeled. A complete listtotal metabolite peak area may be found A complete list of the accounting for at the least ten from the of the detected metabolites are labeled. in Table 3.detected metabolites may be found in Table 3.s 2021, 14,PharmaceuticalsREVIEW 277 x FOR PEER 2021, 14,7 of7 ofCHumanUV / mAU11 six 0 45 C1 CPFPX CRatCUV / mAU30 15 0 45 C1 C2 CPFPXMouseUV / mAU30 C2 15 0 18 CPFPXCDogCPFPXUV / mAU12 6 0 45 C1 C2 CCMini pigCUV / mAU30 15 0 60 C1 CPFPXRhesusUV / mAU40 20 0 0 5 10 15 20 25 30 35 C6 CPFPXTime / minFigure Figure 4. Metaboliteof CPFPX of CPFPX in liver microsomes from SSTR2 Agonist custom synthesis humans from humans and differentDetection four. Metabolite profiles profiles generated generated in liver microsomes and unique animal species. wavelength was 275 nm. Inside the chromatograms,was 275 nm. In peaks accounting for at the very least ten in the peaks animal species. Detection wavelength only metabolite the chromatograms, only metabolite total metabolite accounting for no less than 10 on the from the detected metabolites are labeled. in Table 4. peak area are labeled. A complete listtotal metabolite peak region is usually identified A extensive list of thedetected metabolites is usually located in Table four.RORĪ³ Agonist Compound Pharmaceuticals 2021, 14, 277 Pharmaceuticals 2021, 14, x FOR PEER REVIEWof 19 88 ofFigure 5. Base fragments (a ) for interpretation the in-source fragmentation pathways of in the C8-substituted xanFigure five. Base fragments (a ) for interpretation of with the in-source fragmentation pathwaysthe C8-substituted xanthine compounds. thine compounds. Table two. Metabolites of CBX generated in liver microsomes from different species. Table 2. Metabolites of CBX generated in liver microsomes from a variety of species.Peak A1 APeak A1 ARetention Time Retention (min)Time (min)four.eight five.RetentionFactor Functionalization Retention Functionalization Factor 0.9 1.0.9 1.1 ” H” n.s. ” H” “=”: ” H” 3 n.s. human 1: 0.five mini pig 0.05:31 “=”: ” H” mouse 0.7: 1 human 1:0:0.five rhesus 1 rat 0.05: mini pig0.four: 1 1 dog 0.four: 1 mouse 0.7: 1 n.s. rhesus 0: 1 ” H” n.s. rat 0.4: 1 n.s dog 0.four: 1 n.a.SiteSite of of Functionalization FunctionalR ization n.s. R n.s. “=” @ R ” H” @ F(Pr)Interpretation of Interpretation of Fragments 1 FragmentsSpecies h, r, m, d, mp, rh (h), r, (m), mp, rhh, r, m, d, mp, rh h, r, m, d, mp, rh (h), r, (m), mp, rhSpecies4.8 5.b, c, e, f: + OH – H n.s.”=” d, e: – 2H e,fb, c, e, f: + OH – H n.s.A35.1.A4 A5 A6 A7 CBXA6.0 9.6 ten.4 12.1 16.5.1.1.4 two.9 three.2 three.9 5.”=” @ R ” H” @ n.s. F(Pr) Rn.s. n.s. n.a”=” d, e: – 2H n.s. e,fh, (r), m, d, mp, rh r, (m), mp, (rh)h, r, m, d, mp, rh (h), (r), d, (mp) (h), r, m, d, (mp), (rh) (h), r, m, d, (mp), rhc, e, f: + OH – H n.s. n.s. n.a.A4 n.s. n.s. n.s. (r), (m), mp, (rh) h, human; r, rat; 6.0mouse; d, dog; 1.four mini pig; rh, rhesus; n.s., not specifiable; n.a., not applicable. Brackets indicate minor peaks. 1 acm, mp, cording to Figure five. 2 coelution of two metabolites. three ratio of [M + H]+ intensities (m/z 307 325), e, f: + OH from unfragmented d, mp, rh determined – H A5 9.six 2.9 ” H” R c, h, r, m, spectra. A6 ten.four three.two n.s. n.s. n.s. (h), (r), d, (mp) (h), r, m, d, (mp), A7 12.1 3.9 n.s n.s. n.s. (rh) CBX 16.6 five.7 n.a. n.a n.a. (h), r, m, d, (mp), rhPharmaceuticals 2021, 14,9 ofTable 3. Metabolites of MCBX generated in liver microsomes from numerous species.Peak B1 B2 B3 B4 B5 B6 B7 B8 B9 B10 MCBXRetention Time (min) five.3 five.7 6.3 7.1 eight.0 eight.six 8.9 12.9 21.7 31.six 33.Retention Element 1.1 1.3 1.five 1.