INVESTIGATION OF UNACCEPTABLE IMPURITIES IN THE PHARMACEUTICAL COMPOSITIONS OF METAMIZOLE SODIUM BY HPLC METHOD

Abstract

The method of high-performance liquid chromatography (HPLC) is widely used in recent times for the analysis of medicinal substances, biologically active substances, and medicinal products. The advantages of this method, compared to liquid chromatography (LC) or gas-liquid chromatography (GLC), are low limits of detection of components, reproducibility of analysis results and high selectivity. The implementation of the HPLC method in quality control of dosage forms of finished medicines remains relevant. Metamizole sodium monohydrate is a well-known drug with analgesic, antiinflammatory and antipyretic effects, however, under certain conditions, it can lead to the development of undesirable effects and complications: Quincke’s edema, anaphylactic shock, Stevens-Johnson syndrome, etc. Therefore, checking the quality of the metamizole sodium substance requires a high-tech, thorough analysis and to ensure the possibility of detecting precisely unacceptable accompanying impurities, the presence of which often threatens the health and life of the patient. It should be noted that the chromatographic analysis of the substance metamizole sodium, according to the requirements of the State Pharmacopoeia of Ukraine (SPU) and the British Pharmacopoeia, is performed by the LC method. The purpose of our research is to find new chromatographic conditions and to develop an appropriate technique for determining the purity and chemical composition of metamizole sodium substance with regard to the presence of unacceptable accompanying impurities using the HPLC method; interpretation of the results of instrumental studies with the aim of further in-depth study of the possibility of implementing the HPLC method, as the most promising, in the pharmaceutical analysis of drugs. We have developed the conditions for chromatographic research using the HPLC method of metamizole sodium of the substance for the presence of specified and unspecified impurities, namely, the proposed mobile phase A (3.2 g of triethylamine was dissolved in 1000 ml of water and the pH of the solution was adjusted to 3.0±0.05 using phosphoric acid), mobile phase B – methanol; developed a technique for chromatography using the HPLC method of metamizole sodium substance for the presence of the accompanying impurity Rongalite. According to the results of HPLC chromatography of the metamizole sodium substance in comparison with standard samples of SPU, Rongalite (sodium formaldehyde sulfoxylate dihydrate) was detected – an unacceptable accompanying impurity that can be formed during the synthesis of metamizole sodium, in the composition of the substance with Rt in the interval 1.997–2.009 min. with an excess compared to standard samples.