[Chromatographic determination of novamidazofen in pharmaceutical preparations]

Novamidazofen (metamizol) has been used again as antipyretic and antirheumatic also in abroad recently. In aqueous solutions, such as injections, hydrolysis takes place in its formaldehyde sulfoxylate side chain resulting in an equilibrium mixture of novamidazofen and nor-amidazofen. A high-performance liquid chromatographic method was developed to study the hydrolysis and for the selective and accurate determination of the two components. UV detection at 242 nm wavelength, where the absorbance of novamidazofen and nor-amidazofen were identical, was applied. The rate constants k1 and k3 of the opposite direction reactions as well as K = k1 k3(-1), the hydrolytic equilibrium constant were determined. In aqueous solution, at I-->0 ionic strength and 25 degrees C pK = 3.52 +/- 0.12; 10(4) k1 = 1.74 (+/- 0.25) min-1, P = 0.95. Addition of methanol to the system decreased both the rate and equilibrium constants of the hydrolysis. For the quantitation of novamidazofen Nucleosil C18 column and 20 mmol dm-3 natrium sulphate in methanol-water 40 + 60 V + V eluent were used. The calibration curve was linear in the 20 to 1000 ng range. This method is suitable also for the detection of other, mostly oxidised impurities. A thin-layer chromatographic procedure was also developed on silica GF254 applying acetone-water-ether 30 + 40 + 5 V + V + V eluent. After extraction with chloroform, the oxidised decomposition products can be detected also in injections allowed to stand for a few minutes in an open vessel. The densitometric version of the TLC method was also developed but its precision was lower than that of the HPLC.