Optimization of the Method for Spectrofluorimetric Determination of Aluminum Impurities in Substances

E. V. Vishnyakov, A. A. Tolstikova, Yu. E. Generalova, A. K. Kaldybaeva, Inna Ivanovna Terninko

Drug development & registration, 2023

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DOI 10.33380/2305-2066-2024-13-1-1530
Data confidence 70 medium
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Abstract

Introduction. Evaluation of the content of impurities is the most important step in confirming the safety and efficacy in the quality control of the medicinal product. Aluminum, being an acceptable impurity in a number of pharmaceutical substances, can adversely affect the human body, as a result of which its content is normalized. The admixture of aluminum in the State Pharmacopoeia of the Russian Federation XV is determined by the spectrofluorimetric method using the ligand – 8-hydroxyquinoline in chloroform. In the present work, it is proposed to replace 8-hydroxyquinoline with the more accessible rutin, which also forms fluorescent complexes with metals. This approach involves the exclusion of the stage of extraction of the aluminum complex into chloroform from sample preparation, which improves the accuracy of the technique, and the replacement of chloroform has a positive effect on safety. Aim. To create an alternative approach for the spectrofluorimetric determination of aluminum impurities using rutin and "potassium chloride" as an active pharmaceutical ingredient. Materials and methods. The following substances and reagents were used as research materials: CRS of aluminum ion 1 mg/ml (LLC "EKROSHIM", Russia), CRS of iron ion (II) 1 mg/ml (LLC "EKROSHIM", Russia), CRS of zinc ion 1 mg/ml (LLC "EKROSHIM", Russia), CRS of lead-ion 1 mg/ml (LLC "EKROSHIM", Russia), CRS nickel-ion 1 mg/ml (LLC "EKROSHIM", Russia), CRS copper-ion 1 mg/ml (LLC "EKROSHIM", Russia), chromium (III) cation standard 1 mg/ml (imp., Sigma-Aldrich, USA) rutin (imp., Sichuan Guangsong Pharmaceutical Co., Ltd., China), ammonium acetic acid (imp., Molekula GmbH, Germany), glacial acetic acid (chemically pure, JSC "Base No. 1 Himreaktivov", Russia), potassium chloride (pharmaceutical substance, LLC "MZHR", Russia). The spectrofluorimetric study was carried out on an FL 6500 instrument (PerkinElmer Inc., USA). The aluminum impurity content was also evaluated using an Optima 8000 inductively coupled plasma atomic emission spectrometer (ICP AES) (PerkinElmer Inc., USA) and a Multi-Element Solution standard sample (PerkinElmer Inc., USA). Results and discussion. The approach given in the article eliminates the use of 8-hydroxyquinoline in chloroform and replaces it with rutin in 70 % ethyl alcohol. The aluminum-rutin complex has an excitation wavelength at 445 nm and an emission wavelength at 565 nm. The proposed method was tested on the substance "Potassium chloride" to assess the indicator "Aluminum", the content of which should not exceed 0.0001 %. Method validation was carried out according to three parameters "Specificity", "Linearity" and "Limit of detection". Comparison of the data obtained was carried out using atomic emission spectroscopy, during which the relevance of the technique was proved. Conclusion. An ergonomic approach has been developed for the spectrofluorimetric determination of aluminum impurities using rutin with approbation on the substance "Potassium chloride". The results obtained during the experiment were confirmed by the ICP AES method.