Quantitative bioassay to identify antimicrobial drugs through drug interaction fingerprint analysis.

ABSTRACT

Drug interaction analysis, which reports the extent to which the presence of one drug affects the efficacy of another, is a powerful tool to select potent combinatorial therapies and predict connectivity between cellular components. Combinatorial effects of drug pairs often vary even for drugs with similar mechanism of actions. Therefore, drug interaction fingerprinting may be harnessed to differentiate drug identities. We developed a method to analyze drug interactions for the application of identifying active pharmaceutical ingredients, an essential step to assess drug quality. We developed a novel approach towards the identification of active pharmaceutical ingredients by comparing drug interaction fingerprint similarity metrics such as correlation and Euclidean distance. To expedite this method, we used bioluminescent E. coli in a simplified checkerboard assay to generate unique drug interaction fingerprints of antimicrobial drugs. Of 30 antibiotics studied, 29 could be identified based on their drug interaction fingerprints. We present drug interaction fingerprint analysis as a cheap, sensitive and quantitative method towards substandard and counterfeit drug detection.