Preparation of phenylephrine 3-O-sulfate as the major in vivo metabolite of phenylephrine to facilitate its pharmacokinetic and metabolism studies.


Journal

Journal of pharmacological and toxicological methods
ISSN: 1873-488X
Titre abrégé: J Pharmacol Toxicol Methods
Pays: United States
ID NLM: 9206091

Informations de publication

Date de publication:
Historique:
received: 30 08 2018
revised: 21 11 2018
accepted: 24 11 2018
pubmed: 7 12 2018
medline: 20 3 2019
entrez: 4 12 2018
Statut: ppublish

Résumé

The in vivo disposition and metabolism of phenylephrine have not been establishedby previous analytical methods and there is a lack of available standards for quantitating the metabolites. We pursued and compared the preparation of sulfation metabolites of phenylephrine and its ethyl analog etilefrine via chemical and bio-synthesis. Both sulfates were obtained in higher yield and purity through chemical syntheses compared to biosynthesis. A facile method for the production of phenylephrine 3-O-sulfate and etilefrine 3-O-sulfate was established. These compounds will be useful in the development of analytical assays for studying the pharmacokinetics of phenylephrine and its main route of metabolism in the presence of formulation changes and pharmacogenetic variation.

Identifiants

pubmed: 30502391
pii: S1056-8719(18)30702-0
doi: 10.1016/j.vascn.2018.11.009
pii:
doi:

Substances chimiques

Nasal Decongestants 0
Sulfates 0
Phenylephrine 1WS297W6MV
Etilefrine ZB6F8MY53V

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

66-69

Informations de copyright

Copyright © 2018 Elsevier Inc. All rights reserved.

Auteurs

Zhenxian Zhang (Z)

Departments of Pharmaceutics, Virginia Commonwealth University School of Pharmacy, Richmond, VA 23298-0533, USA.

Yan Zhang (Y)

Medicinal Chemistry, Virginia Commonwealth University School of Pharmacy, Richmond, VA 23298-0533, USA.

Phillip M Gerk (PM)

Departments of Pharmaceutics, Virginia Commonwealth University School of Pharmacy, Richmond, VA 23298-0533, USA. Electronic address: pmgerk@vcu.edu.

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Classifications MeSH