4.

Metabolite identification (MET-ID) studies in plasma samples collected at 30 min (black) and 2 h (red) following oral administration of 18b at a 10-mg/kg equivalent dose of 2-PMPA, compared with a 10 μM standard solution of 18b (green). At 30 min, 18b [m/z = 560.1891; retention time (RT) = 6.11 min] was not detected and dicarboxylic acid intermediate 21 [m/z = 328.0944, RT = 4.04 min] was observed. Intermediate 22 was also detected in plasma samples collected 2 h post-oral administration of 18b, with a 65% decline in the peak area compared to the 30 min plasma samples.