Evaluation of the effect of temperature on the stability and antimicrobial activity of rifampicin quinone

Abstract

Rifampicin is an antibiotic used as a first line treatment for tuberculosis, as well as in the treatment of other infectious diseases. Drug quality is essential for drug efficacy. Determining the stability and activity of Rifampicin Quinone in solution is important in its role as a standard against which to determine Rifampicin quality and in its effect on treatment and AMR development. Poor quality medicines, such as antimicrobials not only increase mortality and morbidity, but can also contribute to the development of antimicrobial resistance (AMR). One common marker of poor quality in Rifampicin samples is the presence of the degradation product Rifampicin Quinone. In this study we have found that Rifampicin Quinone in solution undergoes a chemical conversion to Rifampicin that is temperature dependent. This conversion occurs in physiologically relevant temperatures (30−50 °C) and time scales (24−120 h) and was verified using HPLC and LC–MS methods. Additionally, the conversion of Rifampicin Quinone to Rifampicin results in an increase in antimicrobial activity. We believe that ours is the first study reporting the instability of Rifampicin Quinone, and this instability in solution at these temperatures and time scales raises concerns for its use as a standard in quality testing using liquid chromatography methods and in studies of the effect of Rifampicin Quinone on AMR. Due to the use of Rifampicin Quinone as a standard in determining Rifampicin quality, the instability of Rifampicin Quinone also poses public health concerns, as the incorrect determination of medicine quality risks patient health and may promote the development of AMR.