Detection of Impurities in Anti-infective Generic Drugs in Brazil by Liquid Chromatography-Mass Spectrometry

Abstract

Impurities found in generic medicinesmay contribute to loss of efficacy and adverse side effects when administered to patients suffering from various diseases. Methods of analysis of the quality of drug products are well advanced. Herein, we used Liquid Chromatography with Diode Array Detector coupled to Mass Spectrometry to detect the presence of organic impurities and determine the quantity of the Active Pharmaceutical Ingredient (API) present in representative Antibiotics (2) and Antifungals (2). Possible impurities were detected in some of the generic drugs in both classes of anti-infective drugs. No impurities were detected in the amoxicillin. The compounds 3’-N,N-Di(demethyl) azithromycin (azithromycin impurity E) and 3’-De(dimethylamino)-3’-keto azithromycin (azithromycin impurity N) were detected in generic azithromycin. For itraconazole, the compounds cis-[2-(2,4 dichlorophenyl)-2-(1H-1,2,4-triazol-4-yl-methyl)-1,3-dioxolan-4 yl] methylmethanesulfonate and trans-[2-(2,4-dichlorophenyl)-2-(1H 1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl]methylmethanesulfonate, besides a third substance identified as 2- (2-Butyl) -4-{4-[4-(4-methyloxy-phenyl)-piperazin-1-yl]-phenyl}-2,4-dihydro-[1,2,4]-triazol-3-one were detected as possible impurities. Interestingly, an additional peak was noted in the chromatogram for the generic fluconazole, in addition to the peak of the API; however, none of known impurities of fluconazole were identified. We conclude that tests in addition to bioequivalence measurements may be required to assess post-market generic quality. Such surveillance of generic quality should be performed routinely.