Reactivity considerations in the analysis of glucuronide and sulfate conjugates of diflunisal

Dickinson R.G. and King A.R. (1989) Reactivity considerations in the analysis of glucuronide and sulfate conjugates of diflunisal. Therapeutic Drug Monitoring, 11 6: 712-720.

Author Dickinson R.G.
King A.R.
Title Reactivity considerations in the analysis of glucuronide and sulfate conjugates of diflunisal
Journal name Therapeutic Drug Monitoring   Check publisher's open access policy
ISSN 1536-3694
Publication date 1989-01-01
Sub-type Article (original research)
Volume 11
Issue 6
Start page 712
End page 720
Total pages 9
Subject 2736 Pharmacology (medical)
3004 Pharmacology
1300 Biochemistry, Genetics and Molecular Biology
1303 Specialist Studies in Education
2307 Health, Toxicology and Mutagenesis
2739 Public Health, Environmental and Occupational Health
3005 Toxicology
Abstract Reactivity of glucuronide and sulfate conjugates was taken into account in development of a simple isocratic HPLC method for direct assay of diflunisal (DF) and its acyl glucuronide (DAG), phenolic glucuronide (DPG), and sulfate (DS) conjugates. Whereas DPG was stable over the pH range 0–9, DAG was highly labile at neutral to slightly alkaline pH, undergoing rearrangement (isomerisation via acyl migration), hydrolysis, and, in the presence of methanol, transesterification to DF methyl ester. The 2-, 3-, and 4-O-acyl positional isomers of DAG appeared as three pairs of peaks. Interconversion between partners of each pair occurred even under acidic conditions inhibitory to acyl migration, implicating mutarotation. DS was stable at neutral to slightly alkaline pH, but underwent hydrolysis under relatively strongly acidic conditions. However, this hydrolysis was remarkably catalyzed (e.g., by 1,000-fold) in the presence of solvents (i.e., solvolysis) such as diethyl ether and ethyl acetate. DS (an acid) could not be extracted from aqueous solution because of this acidic solvolysis. Suitable conditions for simultaneous direct analysis (nonextractive, nonconcentrative) of DF and its reactive (DAG and DS) and unreactive (DPG) conjugates were achieved by working at pH of approximately 4.5. The procedure thus developed is suitable for plasma, urine, and bile samples, and has revealed the presence of new, as yet unidentified, metabolites of DF.
Keyword Acyl migration
Diflunisal conjugation
Glucuronides
Sulfates
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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