Simultaneous Determination of Dipyrone Metabolites in Rat Hypothalamus, Cerebrospinal Fluid and Plasma Samples by LC–MS/MS

Abstract

This method is simple and specific for studying dipyrone metabolites after intraperitoneal administration.

Dipyrone metabolite 4‐MAA induces hypothermia and inhibits PGE2‐dependent and ‐independent fever while 4‐AA only blocks PGE2‐dependent fever

“…Considering the evidence discussed earlier, we thought it premature to assume that 4‐MAA and 4‐AA are the antipyretic metabolites of dipyrone relying only on their ability to inhibit PGE 2 synthesis. Therefore, a parallel study was performed in order to develop and validate an analytical method to measure dipyrone metabolites in the plasma, CSF and hypothalamus using LC‐MS/MS (Aguiar et al ., ). Our results demonstrated that all dipyrone metabolites were found in measurable amounts in plasma, CSF and hypothalamus 15 min after dipyrone administration, except 4‐AAA, which was detected only 30 min later in the CSF and hypothalamus.…”

“…Our results demonstrated that all dipyrone metabolites were found in measurable amounts in plasma, CSF and hypothalamus 15 min after dipyrone administration, except 4‐AAA, which was detected only 30 min later in the CSF and hypothalamus. Moreover, significant relationships were observed among plasma, CSF and hypothalamic concentrations for all dipyrone metabolites (Aguiar et al ., ). In line with these results, dipyrone metabolites have been found in the CSF 30 min after oral administration of dipyrone (Cohen et al ., ).…”

“…The concentrations of the dipyrone metabolites 4-MAA, 4-AA, 4-FAA and 4-AAA were determined by LC-MS/MS according to the method described by Aguiar et al (2013). Hypothalamus samples were submitted to ultrasonic disruption in 1 mL of water.…”

“…. 4-MAA was synthesized from dipyrone while 4-FAA and 4-AAA were synthesized from 4-AA as described by Aguiar et al (2013).…”

4‐Methylamino antipyrine determination in human plasma by high‐performance liquid chromatography tandem mass spectrometry

“…Several HPLC methods for 4-methylamino antipyrine determination in biological fluids have been described (Aguiar et al, 2013;Agundez, Martinez, Martin, & Benitez, 1994;Aupanun, Laus, Poapolathep, Owen, & Vullo, 2016;Carretero, Vadillo, & Laserna, 1995;Domínguez-Ramírez et al, 2017;Katz, Granit, Drayer, & Levy, 1984;Ojha, Rathod, & Padh, 2009;Shep et al, 2012;Suarez-Kurtz, Ribeiro, Estrela, Vicente, & Struchiner, 2001). For all of the methods, the C 18 stationary phase is used for chromatographic separation of MAA with the other metabolites of metamizole and endogenous interferences from plasma and urine samples.…”