S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV

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S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV. / Mortensen, R. W.; Corcoran, O.; Cornett, Claus; Sidelmann, U. G.; Lindon, J. C.; Nicholson, J. K.; Hansen, S. H.

In: Drug Metabolism and Disposition, Vol. 29, No. 4, 2001, p. 375-380.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Mortensen, RW, Corcoran, O, Cornett, C, Sidelmann, UG, Lindon, JC, Nicholson, JK & Hansen, SH 2001, 'S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV', Drug Metabolism and Disposition, vol. 29, no. 4, pp. 375-380.

APA

Mortensen, R. W., Corcoran, O., Cornett, C., Sidelmann, U. G., Lindon, J. C., Nicholson, J. K., & Hansen, S. H. (2001). S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV. Drug Metabolism and Disposition, 29(4), 375-380.

Vancouver

Mortensen RW, Corcoran O, Cornett C, Sidelmann UG, Lindon JC, Nicholson JK et al. S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV. Drug Metabolism and Disposition. 2001;29(4):375-380.

Author

Mortensen, R. W. ; Corcoran, O. ; Cornett, Claus ; Sidelmann, U. G. ; Lindon, J. C. ; Nicholson, J. K. ; Hansen, S. H. / S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV. In: Drug Metabolism and Disposition. 2001 ; Vol. 29, No. 4. pp. 375-380.

Bibtex

@article{f84869a706314e598e4dc00291651eba,
title = "S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV",
abstract = "Acyl-migrated isomers of drug beta -1-O-acyl glucuronides have been implicated in drug toxicity because they can bind to proteins. The acyl migration and hydrolysis of S-naproxen-beta -1-O-acyl glucuronide (S-nap-g) was followed by dynamic stopped-flow HPLC-H-1 NMR and HPLC methods. Nine first order rate constants in the chemical equilibrium between six species (S-nap-g, its alpha/beta -2-O-acyl, alpha/beta -3-O-acyl, alpha/beta -4-O-acyl, and alpha -1-O-acyl-migration isomers, and S-naproxen aglycone) were determined by HPLC-UV studies in 25 mM potassium phosphate buffer, pH 7.40, 25 mM potassium phosphate buffer in D2O pD 7.40, and 25 mM potassium phosphate buffer in D2O pD 7.40/MeCN 80:20 v/v (HPLC-H-1 NMR mobile phase). In the 25 mM potassium phosphate buffer (pH 7.40) the acyl-migration rate constants (h(-1)) were 0.18 (S-nap-g-alpha/beta -2-O-acyl isomer), 0.23 (alpha/beta -2-O-acyl-alpha -1-O-acyl), 2.6 (alpha -1-O-acyl-alpha/beta -2-O-acyl), 0.12 (alpha/beta -2-O-acyl-alpha/beta -3-O-acyl), 0.048 (alpha/beta -3-O-acyl- alpha/beta -2-O-acyl), 0.059 (alpha/beta -3-O-acyl-alpha/beta -4-O-acyl), and 0.085 (alpha/beta -4-O-acyl-alpha/beta -3-O-acyl). The hydrolysis rate constants (h(-1)) were 0.025 (hydrolysis of S-nap-g) and 0.0058 (hydrolysis of all acyl-migrated isomers). D2O and MeCN decreased the magnitude of all nine kinetic rate constants by up to 80{\%}. The kinetic rate constants for the degradation of S-nap-g in the mobile phase used for HPLC-H-1 NMR determined using HPLC-UV could predict the results obtained by the dynamic stopped-flow HPLC-H-1 NMR experiments of the individual acyl-migrated isomers. It is therefore recommended that beta -1-O-acyl glucuronide degradation kinetics be investigated by HPLC-UV methods once the identification and elution order of the isomers have been established by HPLC-H-1 NMR.",
keywords = "human serum-albumin internal acyl migration coupled hplc-nmr tandem mass-spectrometry in-vitro positional isomers covalent binding 1-o-acyl glucuronide biochemical pathways salicylic-acid",
author = "Mortensen, {R. W.} and O. Corcoran and Claus Cornett and Sidelmann, {U. G.} and Lindon, {J. C.} and Nicholson, {J. K.} and Hansen, {S. H.}",
year = "2001",
language = "Udefineret/Ukendt",
volume = "29",
pages = "375--380",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "4",

}

RIS

TY - JOUR

T1 - S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV

AU - Mortensen, R. W.

AU - Corcoran, O.

AU - Cornett, Claus

AU - Sidelmann, U. G.

AU - Lindon, J. C.

AU - Nicholson, J. K.

AU - Hansen, S. H.

PY - 2001

Y1 - 2001

N2 - Acyl-migrated isomers of drug beta -1-O-acyl glucuronides have been implicated in drug toxicity because they can bind to proteins. The acyl migration and hydrolysis of S-naproxen-beta -1-O-acyl glucuronide (S-nap-g) was followed by dynamic stopped-flow HPLC-H-1 NMR and HPLC methods. Nine first order rate constants in the chemical equilibrium between six species (S-nap-g, its alpha/beta -2-O-acyl, alpha/beta -3-O-acyl, alpha/beta -4-O-acyl, and alpha -1-O-acyl-migration isomers, and S-naproxen aglycone) were determined by HPLC-UV studies in 25 mM potassium phosphate buffer, pH 7.40, 25 mM potassium phosphate buffer in D2O pD 7.40, and 25 mM potassium phosphate buffer in D2O pD 7.40/MeCN 80:20 v/v (HPLC-H-1 NMR mobile phase). In the 25 mM potassium phosphate buffer (pH 7.40) the acyl-migration rate constants (h(-1)) were 0.18 (S-nap-g-alpha/beta -2-O-acyl isomer), 0.23 (alpha/beta -2-O-acyl-alpha -1-O-acyl), 2.6 (alpha -1-O-acyl-alpha/beta -2-O-acyl), 0.12 (alpha/beta -2-O-acyl-alpha/beta -3-O-acyl), 0.048 (alpha/beta -3-O-acyl- alpha/beta -2-O-acyl), 0.059 (alpha/beta -3-O-acyl-alpha/beta -4-O-acyl), and 0.085 (alpha/beta -4-O-acyl-alpha/beta -3-O-acyl). The hydrolysis rate constants (h(-1)) were 0.025 (hydrolysis of S-nap-g) and 0.0058 (hydrolysis of all acyl-migrated isomers). D2O and MeCN decreased the magnitude of all nine kinetic rate constants by up to 80%. The kinetic rate constants for the degradation of S-nap-g in the mobile phase used for HPLC-H-1 NMR determined using HPLC-UV could predict the results obtained by the dynamic stopped-flow HPLC-H-1 NMR experiments of the individual acyl-migrated isomers. It is therefore recommended that beta -1-O-acyl glucuronide degradation kinetics be investigated by HPLC-UV methods once the identification and elution order of the isomers have been established by HPLC-H-1 NMR.

AB - Acyl-migrated isomers of drug beta -1-O-acyl glucuronides have been implicated in drug toxicity because they can bind to proteins. The acyl migration and hydrolysis of S-naproxen-beta -1-O-acyl glucuronide (S-nap-g) was followed by dynamic stopped-flow HPLC-H-1 NMR and HPLC methods. Nine first order rate constants in the chemical equilibrium between six species (S-nap-g, its alpha/beta -2-O-acyl, alpha/beta -3-O-acyl, alpha/beta -4-O-acyl, and alpha -1-O-acyl-migration isomers, and S-naproxen aglycone) were determined by HPLC-UV studies in 25 mM potassium phosphate buffer, pH 7.40, 25 mM potassium phosphate buffer in D2O pD 7.40, and 25 mM potassium phosphate buffer in D2O pD 7.40/MeCN 80:20 v/v (HPLC-H-1 NMR mobile phase). In the 25 mM potassium phosphate buffer (pH 7.40) the acyl-migration rate constants (h(-1)) were 0.18 (S-nap-g-alpha/beta -2-O-acyl isomer), 0.23 (alpha/beta -2-O-acyl-alpha -1-O-acyl), 2.6 (alpha -1-O-acyl-alpha/beta -2-O-acyl), 0.12 (alpha/beta -2-O-acyl-alpha/beta -3-O-acyl), 0.048 (alpha/beta -3-O-acyl- alpha/beta -2-O-acyl), 0.059 (alpha/beta -3-O-acyl-alpha/beta -4-O-acyl), and 0.085 (alpha/beta -4-O-acyl-alpha/beta -3-O-acyl). The hydrolysis rate constants (h(-1)) were 0.025 (hydrolysis of S-nap-g) and 0.0058 (hydrolysis of all acyl-migrated isomers). D2O and MeCN decreased the magnitude of all nine kinetic rate constants by up to 80%. The kinetic rate constants for the degradation of S-nap-g in the mobile phase used for HPLC-H-1 NMR determined using HPLC-UV could predict the results obtained by the dynamic stopped-flow HPLC-H-1 NMR experiments of the individual acyl-migrated isomers. It is therefore recommended that beta -1-O-acyl glucuronide degradation kinetics be investigated by HPLC-UV methods once the identification and elution order of the isomers have been established by HPLC-H-1 NMR.

KW - human serum-albumin internal acyl migration coupled hplc-nmr tandem mass-spectrometry in-vitro positional isomers covalent binding 1-o-acyl glucuronide biochemical pathways salicylic-acid

M3 - Tidsskriftartikel

VL - 29

SP - 375

EP - 380

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 4

ER -

ID: 38061881