Table 2

First order kinetic rate constants fitted for the degradation experiments in reaction media 1, 2, and 3 monitored by HPLC-UV

k (h−1)Reaction Medium 1 H2O pH 7.40Reaction Medium 2 D2O pD 7.40Reaction Medium 3 D2O pD 7.40/MeCN (80:20)
β1-D0.0260.00830.0049
β1-20.180.130.072
2-α10.230.0720.072
α1-22.61.11.3
2-30.120.0400.023
3-20.0480.0260.014
3-40.0590.0340.019
4-30.0850.0590.058
X-D0.00580.00330.0023
Ratio am/h6.915.714.7
Ratio 2/1α11.315.318.1
Ratio 2/30.40.70.6
Ratio 3/41.41.73.0
Σs2 20.22.30.81

Rate constants are shown in the reaction scheme depicted in Fig. 1. X-D is the hydrolysis of the acyl-migrated isomers to S-naproxen aglycone (D = drug), which is fitted as one parameter (kX-D = kα1-D= k2-D = k3-D =k4-D). The pseudoequilibrium concentration ratios between the α-1-, α/β-2-, α/β-3-, and α/β-4-O-acyl isomers are calculated by the ratio of the reversible acyl-migration first order rate constants in the equilibrium. Ratio am/h is the ratio between acyl migration (kβ1-2) and hydrolysis (kβ1-D) for S-nap-g. Σs2 is the sum of squares from the kinetic fitting to the analytical data for each reaction medium.