Determinação de alguns produtos de degradação da azitromicina por cromatografia líquida de alta eficiência UV-vis em formas farmacêuticas comprimido revestido

Abstract

Azithromycin (AZM) is a broad-spectrum, semi-synthetic antibiotic from the macrolide family, used for decades to treat infections caused by bacteria, such as pharyngitis and tonsillitis. During the pandemic, its possible repositioning against the new coronavirus (SARS-Cov-2) was widely publicized, however, the World Health Organization (WHO) does not recommend this therapy. Drugs may contain impurities, which are inevitably produced during their synthesis route, but may also originate throughout the shelf life of the drug, as degradation products. In the case of AZM, these impurities can reduce the antibacterial activity and increase the toxicity of the drug. Therefore, regulatory authorities describe that the impurity profile of a medicine is a critical attribute of quality (CQA) and safety and thus, it has been triggering greater technical rigor and global guidelines in this control. Impurities that exceed 0.1% must have their structures confirmed to comply with the limits proposed by ICH (International Conference on Harmonization of Requirements for Registration of Pharmaceutical Products for Human Use). Therefore, it is important to identify AZM impurities, which are its structural analogues, and monitor their presence and quantity in the medicine. This work proposed to evaluate the analytical methods available in official compendia and make the necessary adjustments for the analytical suitability by HPLC UV-vis detector in a multinational pharmaceutical industry (since it had not been achieved previously), with consequent validation of the analytical method for evaluating the known and unknown organic impurities arising from the degradation of AZM in the medicine (finished product), demonstrating its selectivity, precision, accuracy, linearity and robustness, in accordance with the specifications contained in RDC nr. 166/17. Finally, monitor the quality of six batches from five different registration holders available on the Brazilian market