Simultaneous determination of dipyrone metabolites in rat hypothalamus, cerebrospinal fluid and plasma samples by LC-MS/MS

Author(s)

Aguiar, Fernando A. ^[1] ; Malvar, David do C. ^[2] ; Vaz, Artur de L. L. ^[3] ; Calixto, Leandro A. ^[2] ; Clososki, Giuliano C. ^[3] ; de Gaitani, Cristiane M. ^[1] ; de Souza, Gloria E. P. ^[2] ; Jabor, Valquiria A. P. ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, BR-14040149 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040149 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Res Ctr Nat & Synthet Prod, BR-14040149 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: BIOANALYSIS; v. 5, n. 21, p. 2631-2645, NOV 2013.
• Web of Science Citations: 2

Abstract

Background: After oral administration dipyrone is rapidly hydrolyzed to 4-methylaminoantipyrine, which is absorbed and further metabolized to 4-formylaminoantipyrine and to 4-aminoantipyrine, which is acetylated by a polymorphic N-acetyltransferase system to 4-acetylaminoantipyrine. To evaluate the presence of dipyrone metabolites in different rat matrices after intraperitoneal administration, an analytical method was developed and validated. Methodology: The four main dipyrone metabolites were extracted from plasma, cerebrospinal fluid and hypothalamus samples by LLE prior to LC-MS/MS. Results: Standard calibration graphs for all metabolites were linear (r > 0.99). The intra- and inter-day precision and accuracy values were both inferior to 15%. Conclusion: This method is simple and specific for studying dipyrone metabolites after intraperitoneal administration. (AU)

• FAPESP's process: 08/09443-4 - Antipyretic effect of the main dipyrone metabolites on febrile response induced by LPS and Tityus serrulatus scorpion venom
• Grantee: David do Carmo Malvar
• Support Opportunities: Scholarships in Brazil - Doctorate