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Abstract

Background: Metamizole (Dipyrone) is widely used and has effective analgesic, antipyretic, and antispasmodic properties. After oral or intravenous administration, dipyrone is rapidly hydrolyzed to the active moiety 4-methylaminoantipyrine. Aim: The aim of this study was to assess the bioequivalence of 2 oral formulations of Metamizole 500 mg. Methods: This double blind, randomized, single-dose, 2-period crossover study in healthy Indian adult volunteers was conducted at PERD Centre, Ahmedabad. Subjects received Metamizole 500 mg of either test or reference formulation with a washout period of 7 days. After study drug administration, serial blood samples were collected over a period of 24 hours. Plasma concentration of 4-methylaminoantipyrine was measured by pre-validated LC-MS method. Pharmacokinetic (PK) parameters C max , T max , t 1/2 , AUC 0-t , AUC 0-∞ , and k el , were determined for test and reference formulations. The formulations were to be considered bioequivalent if the log-transformed ratios of C max , AUC 0-t , and AUC 0-∞ were within the predetermined bioequivalence range of 80% to 125%. Results: A total of 14 subjects were enrolled. No significant differences were found based on analysis of variance, with mean values and 90% confidence intervals of test/reference ratios for these parameters as follows: C max , 18.24 versus 18.44 μg/mL (92.68 -106.61); AUC 0-t , 92.97 Versus 91.37 μg.hr/mL (89.49 -113.09); and AUC 0-∞ , 96.64 Versus 94.65 μg.hr/mL (92.31 -111.63). Conclusion: Since the 90% confidence intervals for C max , AUC 0-t , and AUC 0−∞ were within the interval of 80-125%, it was concluded that both formulations were bioequivalent, according to both the rate and extent of absorption.

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.…”

“…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. Generally, a liquid-liquid extraction sample preparation technique into ethyl acetate or chloroform with sodium hydroxide additive is described (Agundez et al, 1994;Aupanun et al, 2016;Katz et al, 1984;Ojha et al, 2009;Shep et al, 2012). The large volume of extraction solvent (4-5 ml) requires a long time for evaporation, which is undesirable when a large number of samples need to be analyzed.…”