Article Figures & Data
Figures
- Fig. 1.
LB base peak chromatogram (A) and HCD MS2 of protonated molecular ion ([M+H]+) m/z 292.1907 (B).
- Fig. 2.
Proposed metabolic scheme for LB in rat, rabbit, and human ocular and liver S9 fractions. Alternative sites of conjugative metabolism are denoted with dashed arrows.
- Fig. 3.
(A) Depletion of LB (1 µM) in OS9 and LS9 fractions across rats, rabbits, and humans over 60 minutes. Data are represented as mean values of duplicate experiments. Values represent percentage of LB remaining. (B) Relative formation of DHLB, the active metabolite of LB (M11), in OS9 and LS9 across rats, rabbits, and humans is presented as a percentage of the highest MS peak area of M11 at 60 minutes (i.e., RbtLS9 = 100%). Incubations for metabolite identification were carried out at 10 µM LB concentration. Absolute quantification was not possible without an authentic reference standard.
Tables
- TABLE 1
Metabolites of LB
Structures and high-resolution LC-MSn data of in vitro LB metabolites identified in rat, rabbit, and human LS9 and OS9. Proposed metabolite structures are shown, and alternative sites of conjugative metabolism are noted with dashed arrows. Fragmentation is provided for the proposed structures; however, the site of protonation is not provided. A retention time for each metabolite is provided.
Metabolite Measured [M+H]+ Theoretical [M+H]+ Mass Accuracy (ppm) Key Collision Induced Dissociation Product Ions Proposed Structure and Fragmentation Fraction(s) in Which the Metabolite Was Identified Retention Time (min) M1 466.2063 466.20721 2.0 410.1451, 234.1152a 
RLS9, RbtLS9 10.60 M2 484.2159 484.2177 3.7 308.1877 RLS9, HLS9 10.65 M3 500.2107 500.2126 3.8 324.1822a HOS9, RLS9 10.90 M4 310.1999 310.2013 4.5 254.1418, 236.1311a RLS9, HLS9 11.01 M5 484.2159 484.2177 3.7 308.1875a RLS9 11.21 M6 500.2107 500.2126 3.8 324.1828a HOS9, RLS9 11.30 M7 324.1809 324.1805 1.2 306.1728a HOS9, RLS9, RbtLS9 11.33 M8 310.1999 310.2013 4.5 254.1410, 236.1304a HOS9, RLS9, RbtLS9, HLS9 11.56 M9 308.1838 308.1856 5.8 252.1251, 234.1137, 217.0876a All ocular and liver fractions 12.56 M10 290.1738 290.1751 4.5 234.1114 All liver fractions 12.63 M11 294.2046 294.2064 6.1 220.1344a All ocular and liver fractions 13.11 M12 324.1809 324.1805 1.2 252.1179a RLS9 13.30 M13 308.1838 308.1856 5.8 236.1280a RLS9, HLS9 13.68 M14 350.1964 350.1962 0.6 NA RLS9, RbtLS9 13.80 M15 350.1964 350.1962 0.6 NA RLS9 15.07 M16 334.2013 334.2013 0.0 278.1382, 261.1120, 201.0905 All ocular and liver S9 fractions 15.81 [M+H]+, protonated molecular ion; NA, not applicable.
↵a Base peak, m/z 164, in product ion spectra is a resonance ion for this instrument.
Data Supplement
Files in this Data Supplement:
- Supplemental Figures -
Supplemental Figure 1 - Representative CID MS/MS spectrum of levobunolol metabolites, M1-M16 (A-P)
Levobunolol metabolite characterization description
- Supplemental Figures -
In this issue
Ocular Metabolism of Levobunolol
