Drug Metabolism in Drug Design and Development Basic Concepts and Practice

of NS bond. Based on these data, the major metabolite M11 was proposed
as dihydroziprasidone (Scheme 11.3).

11.4.4 Accurate Mass Measurement

Accurate mass measurements are often used for the identification or
confirmation of the molecular formulas of drug metabolites. The analytical
utility of high resolution mass spectrometry began with the introduction of
double-focusing magnetic sector instruments, which could routinely achieve

S

N

N N

N
O

Cl

H

N N SH

N

O

Cl

NH

H

Ziprasidone, m/z (^413) M11, m/z 415
SCHEME 11.3 Structures of ziprasidone and its major metabolite M11 in hepatic
cytosolic fractions.
FIGURE 11.3 CID product ion spectra of metabolite M11 before (a) and after (b)
H/D exchange. Reprinted from Miao et al. (2005) with permission of the American
Society for Pharmacology and Experimental Therapeutics.
342 APPLICATION OF LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY