Table 1

Characteristic 1H NMR signals used for the quantitation of isomers in the dynamic 1H NMR degradation experiments

δ HMultiplicityIsomerAssignment
5.52dβ-1H1
5.18dα-4H1
5.11mα-3H1+ H3
4.95dβ-3H3
4.66mα/β-2H2
4.09dβ-4H5
1.59dα-1−CH3
1.42d S-Naproxen−CH3

Chemical shifts are referenced to acetonitrile at δ 2.0. Glucuronide ring protons are numbered according to Fig. 1. The signal at δ 5.11 for the α-3-O-acyl isomer is a superposition of the H1′ and H3′ protons; thus, the integrated signals are divided by 2 prior to kinetic analysis to get the signal corresponding to one proton. The CH3 group used for quantitation of the α-1-O-acyl isomer andS-naproxen aglycone is the α-methyl group in the acetic acid moiety of S-naproxen. This signal is divided by 3 prior to kinetic analysis to get the signal corresponding to one proton. For the β-1-O-acyl glucuronide and the α/β-2-, α/β-3-, and α/β-4-O-acyl isomers this methyl group appears as an unresolved band in the region δ 1.51 to 1.53 and cannot be used for quantitation.

  • d, doublet; m, multiplet.