Quality of Active Pharmaceutical Ingredients Present on Algerian Soil: Control of Impurities of Ciprofloxacin, Metronidazole and Fluconazole.

ABSTRACT

INTRODUCTION: The medicine quality is defined by its aptitude to meet certain requirements declared by the regulatory authorities. Among these, impurities control which constitutes the major fear of pharmaceutical manufacturers in efficiency and safety terms. Nowadays, in many developing countries, the presence of poor quality drugs is common, for this reason, an increased control should be instituted including impurities which represent a serious public health problem threatening the efficacy and the safety medicines, because of their nocuous repercussions on health. The objective of this study is to verify that impurities in certain APIs Ciprofloxacin, Metronidazole and Fluconazole actually collected on Algerian soil meet the impurity requirements. MATERIALS AND METHODS: An observational experimental study was carried out from 1st December 2013 to 31st December 2017, on impurities control in the APIs of Ciprofloxacin, Metronidazole and Fluconazole medicines registered in the Algerian Medicines Nomenclature and marketed in Algeria. All samples collected were analyzed to detect, quantify and evaluate impurties for rigorous control of three categories of impurties, such as Organic related-impurities analysis by High-Pressure Liquid Chromatography with UV Detector (HPLC-UV), Elemental-impurities analysis by Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) and Residual Solvents-impurities analysis by Headspace Gas Chromatography with Flame Ionization Detection (HS-GC-FID). RESULTS AND DISCUSSION: 18 samples collected from 11 laboratories among 27 requested. 22% of non-conformities were detected, including 5.5% Indian origin, 5.5% Spanish origin, 5.5% French origin and 5.5% Chinese origin. These non-conformity cases are due to the high rate of degradation product-impurity for C5 sample, Cobalt-impurity and Nickel-impurity contents exceeding the required limits for C4 and M3 samples respectively, Methanol-impurity and Toluene-impurity contents exceeding the authorized limits for M2 and F3 samples respectively. CONCLUSION: This study concluded that samples non-compliance rate is high because of certain impurities detection exceeding the safety standards. So, we interpellate the health authorities to ensure the APIs impurities control before being put into the manufacturing process in order to prevent the potentially serious health problems that are difficult to control.