Drug Metabolism in Drug Design and Development Basic Concepts and Practice

pair of 340 and 525 nm. The final quantitative result of dGSH adduct
formation is expressed as percentage of initial compound concentration. The
positive control,R-(+)-pulegone, usually produces 8–10% of dGSH adduct
under the above conditions (Fig. 14.5). The quantitative analysis of dGSH
adducts of some model compounds are shown in Table 14.1.

15

20

25

30 Blank R-(+)-pulegone

R-(+)-pulegone adduct

dGSH m/z687 (-ESI)

a

Time (min)

8 12162024283236

Fluorescence (mV)

0

5

10

200 250 300 350 400 450 500 550 600 650 700

m/z

20

40

60

80

100

(^252434)
234 361
MS^2
m/z 687
0
487
505
Relative abundance (%)
b 2
FIGURE 14.5 LC/Fluorescence/MS analysis of dGSH adduct ofR-(+)-pulegone. (a)
Fluorescence chromatograms of samples from HLM incubation ofR-(+)-pulegone in
the presence of NADPH and dGSH. Dashed profile was from blank sample withoutR-
(+)-pulegone. (b), ESI–MS^2 spectrum ofR-(+)-pulegone adduct obtained by CID of
the [M-H]ion atm/z687 (negative ionization mode). The fragment ions were all
originated from cleavage of the dGSH moiety [(Gan et al, 2005).]
GLUTATHIONE,N-ACETYLCYSTEINE, AND POTASSIUM CYANIDE 459