title: Simultaneous determination of dipyrone metabolites in rat hypothalamus, cerebrospinal fluid and plasma samples by LC-MS/MS.
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.
  
  
  METHODS
  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%.
  
  
  CONCLUSIONS
  This method is simple and specific for studying dipyrone metabolites after intraperitoneal administration.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Aguiar
authors.forename: David do C
authors.initials: Ddo C
authors.lastname: Malvar
authors.forename: Artur de L L
authors.initials: Ade L
authors.lastname: Vaz
authors.forename: Leandro A
authors.initials: LA
authors.lastname: Calixto
authors.forename: Giuliano C
authors.initials: GC
authors.lastname: Clososki
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: de Gaitani
authors.forename: Glória E P
authors.initials: GE
authors.lastname: de Souza
authors.forename: Valquíria A P
authors.initials: VA
authors.lastname: Jabor
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004177:Dipyrone / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D007031:Hypothalamus / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004177:Dipyrone