Synonyms.

NSC-73205; Aminopyrinesulfonate Sodium; Analginum; Metamizole; Metamizole Sodium; Metamizolum Natricum; Methampyrone; Methylmelubrin; Natrium Novaminsulfonicum; Noramidazophenum; Noraminophenazonum; Novamidazofen; Sodium Noramidopyrine Methanesulphonate; Sulpyrine. Proprietary names. Algi; Analgin; Baralgin; Berlosin; Conmel; Dolemicin; Dolocalma; Inalgon Neu; Lasain; Metilon; Minalgin; Neo Melubrina; Nevralgina; Nolotil; Novalgin(e); Novaminsulfon; Optalgin; Pyril; Trisalgina; Unagen. It is an ingredient of many proprietary preparationssee Martindale, The complete drug reference, 33rd Edn., London, Pharmaceutical Press, 2002. Sodium-[(2,3dihydro1,5dimethyl3oxo2phenyl1H -pyrazol4 yl)methylamino]methanesulphonate Monohydrate C13H16N3NaO4S,H2O = 351.4 CAS68893 (anhydrous); 5907380 (monohydrate) A white or yellowishwhite crystalline powder. M.p. 172. Soluble 1 in 1.5 of water and 1 in 30 of ethanol; practically insoluble in ether, acetone, benzene, and chloroform. Colour Tests. Ferric Chlorideviolet; FolinCiocalteau Reagentblue; Liebermann's Test (100)blue; Mandelin's Testbrown; Nitrous Acidtransient blue. Thinlayer Chromatography. System TARf 84; system TBRf 00; system TCRf 01; system TD Rf 00; system TERf 02; system TFRf 00; system TLRf 02; system TADRf 02; system TAE Rf 85; system TAFRf 59; system TAJRf 00; system TAKRf 00; system TALRf 24. (Acidified iodoplatinate solution, white.) Gas Chromatography. System GAM (bisdesalkyl-) RI 1955, M (desalkyl-)AC RI 2395; system GB dipyrone RI 2069. High Performance Liquid Chromatography. System HDk 0.1; system HW k 0.45; system HXRI 316; system HYRI 194; system HZretention time 1.4 min. Ultraviolet Spectrum. Aqueous acid258 nm (A11=266a). 1172 / 6957 Infrared Spectrum. Principal peaks at wavenumbers 1672, 1064, 1179, 1163, 1208, 1639 cm1 (KBr disk).

Mass Spectrum. Principal ions at m/z 56, 42, 83, 57, 77, 51, 97, 54. Quantification HIGH PERFORMANCE LIQUID CHROMATOGRAPHY. In plasma or urine: limits of detection 1 mg/L for dipyrone and 250 g/L for 4methylaminophenazone, UV detectionG. Asmardi and F. Jamali,J. Chromatogr.,1983, 277 (28) B Biomed. Appl., 183189. In plasma or urine: dipyrone metabolites, limits of detection 0.1 mg/L in plasma and 2 mg/L in urine, UV detectionD. Damm,Arzneimittelforschung,1989, 39, 14151417. In urine: dipyrone and its metabolites and aminopyrine, UV detectionJ. A. Agundez et al.,Ther. Drug Monit.,1994, 16, 316322. Disposition in the Body. Rapidly hydrolysed in gastric juice after oral administration to the active metabolite 4methylaminophenazone, which is metabolised after absorption to 4formylaminophenazone, 4 aminophenazone, and 4acetylaminophenazone. About 70% of a dose is excreted in the urine in 24 h as metabolites. Dipyrone metabolites are excreted in breast milk. THERAPEUTIC CONCENTRATION Following a single oral dose of 1 g given to 12 slow acetylators and 11 rapid acetylators (determined with reference to dapsone), the following mean peak plasma concentrations (mg/L, time in h) were reported: Slow acetylators Rapid acetylators 4-Acetylaminophenazone 1.6 (16.1) 4.4 (10.0) 4-Aminophenazone 2.7 (6.7) 1.6 (3.2) 4-Formylaminophenazone 1.8 (7.7) 2.5 (6.6) 4-Methylaminophenazone 10.0 (1.6) 11.0 (1.2) 1173 / 6957 [M. Levy et al.,Eur. J. Clin. Pharmacol.,1984, 27, 453458.] In 12 subjects given single oral doses of a test and reference preparation of dipyrone 1 g, the mean peak plasma concentrations of 4methylaminophenazone, 4formylamino phenazone, 4aminophenazone, and 4 acetylaminophenazone were 17.19 and 16.92 mg/L (test and reference), 1.6 and 1.84 mg/L, 2.94 and 2.89 mg/L, and 1.93 and 1.86 mg/L at 1.42 and 1.46 h, 6.2 and 7.0 h, 4.4 and 4.4 h, and 11.3 and 11.6 h, respectively. 4 of the subjects were rapid and 8 were slow acetylators; the peak plasma concentration (or the test preparation) differed significantly between the two acetylator types only for 4 aminophenazone (16.98 vs 18.52 for slow vs rapid acetylators) and 4acetylaminophenazone (1.38 vs 4.38 mg/L). [N. Bacracheva et al.,Arzneimittelforschung,1995, 45, 282285.] TOXICITY. The estimated minimum lethal dose is 5 g, but fatalities from acute poisoning are rare. A 56yearold man died after ingesting up to 20 g dipyrone, 2 g baclofen, and 0.15 g oxybutynin; terazosin,

aspirin, defibrotide, and laxatives also may have been ingested. Postmortem examination, performed a few hours after death, revealed dipyrone, baclofen, and oxybutynin concentrations, respectively, of 106, 669, and 0.1 mg/L in the blood and 774 mg/L, 215 mg/L, and trace amounts in the urine. [N. De Giovanni and E. dAloha,Forensic Sci. Int.,2001, 123, 2632.] HALFLIFE. Plasma halflife, 4acetylaminophenazone about 10.6 h, 4amino phenazone about 5 h, 4 formylaminophenazone about 10 h, and 4methylaminophenazone about 3.3 h. Dose. 0.5 to 4 g daily in divided doses.