Stereospecific pH-dependent degradation kinetics of R- and S-naproxen-beta-l-O-acyl-glucuronide.

Abstract:

:The hydrolysis and acyl migration of biosynthetic S-naproxen-beta-l-O-acyl glucuronide (I) and R-naproxen-beta-l-O-acyl glucuronide (II) was followed by HPLC. Nine first-order kinetic rate constants for the hydrolysis and acyl migration between the beta-l-O-acyl glucuronide, its alpha/beta-2, alpha/beta-3-, alpha/beta-4-, and alpha-1-O-acyl isomers and naproxen aglycone were determined for I and II at pH 7.00, 7.40 and 8.00 at 37 degrees C by kinetic simulation. For I the 3-O-acyl isomer was the most stable isomer as the pseudo-equilibrium ratio for the major acyl-migrated isomers was 1:1.5:0.9 (2-O-acyl isomer:3-O-acyl isomer:4-O-acyl isomer). The 3- and 4-O-acyl isomers of II were equally stable as the pseudo-equilibrium ratio for the major acyl-migrated isomers was 1:1.4:1.4 (2-O-acyl isomer:3-O-acyl isomer:4-O-acyl isomer). For both I and II, the pseudo-equilibrium ratio between the major 2-O-acyl isomer and the minor alpha-l-O-acyl isomer was 10:1 (2-O-acyl isomer:alpha-l-O-acyl isomer). The pseudo-equilibrium found for the major acyl-migrated isomers of I and II in the present study corresponds with the pattern previously published for R- and S-ketoprofen-beta-l-O-acyl glucuronide acyl-migrated isomers, suggesting that these findings may be general for acyl-migrated beta-l-O-acyl glucuronides of enantiomeric 2-arylpropionic acids.

journal_name

Chirality

journal_title

Chirality

authors

Mortensen RW,Sidelmann UG,Tjørnelund J,Hansen SH

doi

10.1002/chir.10047

subject

Has Abstract

pub_date

2002-05-05 00:00:00

pages

305-12

issue

4

eissn

0899-0042

issn

1520-636X

journal_volume

14

pub_type

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