Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 12.11 Metabolite identification by using NMR spectroscopy.Metabolicreaction

Metabolite identification examples

NMR indications

Confirmation method

and comments

1. Dealkylation

FC^3

O

NH

FC^3

O

NH

2

Nor fluxetine

Fluoxetine

The methyl group at

d2.98

(s, 3H) disappeared

There is no need for further

confirmation

The

a-CH

2

group shifted from

d2.82 to

d2.98 ppm

2. Aliphatic

hydroxylation(Gerhard et al.,2003)

N

N R

N

N R

HO

The methyl group at

d2.45(s, 3H) disappeared

There is no need for further

confirmation

A new peak appeared at

d4.71 ppm (s, 2H), which ischaracteristic for a methylenealcohol

(Chando et al.,1998)

N

N

O

NN

NHN

N

N

O

OH

NN

NHN

h

ydrox

yl-irbesartan

Irbesartan

The methyl proton shifted from

d0.80 to

d1.00 ppm and its

coupling pattern changedfrom a triplet to a doublet

The methyl and methine groups

indeed belonged to the samespin system could beconfirmed by the 2D COSYexperiment

The

a-CH group shifted from

d1.23 (m, 2H) to

d3.58

(m, 1H), which is consistentwith a secondary alcohol

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