Simultaneous determination of rifampicin, isoniazid, pyrazinamide and ethambutol in fixed-dose combination antituberculosis pharmaceutical formulations: a review

According to the World Health Organization, rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride are the first-line drugs used to treat tuberculosis - an infectious disease caused by Mycobacterium tuberculosis. Since 2010, tuberculosis has been treated with a fixed-dose combination containing the four drugs in only one tablet, called 4-FDC, which has simplified the treatment, minimized prescription errors and increased patients' adherence to their treatment regime. Within this context, the present review aims to show the evolution of different analytical methods that have been applied to simultaneous 4-FDC content determination in pharmaceutical formulations, such as high performance liquid chromatography, ultrahigh performance liquid chromatography, thin layer chromatography and capillary electrophoresis as separation techniques and molecular spectroscopic techniques associated with chemometric approaches, such as UV, Raman, Fourier transform infrared and near infrared.