Bioanalysis and Stability of Polymyxins

Clinical use of the polymyxin antibiotics began approximately 10 years after their discovery in the late 1940s. Their concentrations in biological fluids were measured using microbiological methods. These methods were reasonably accurate for measuring the active polymyxin base, such as polymyxin B and colistin (polymyxin E), but were used inappropriately for measuring the concentrations of “colistin” in humans or animals following the administration of colistimethate, also known as colistin methanesulphonate (CMS). The use of polymyxins for systemic infections waned in the 1970s because of their toxicity and the preference for other antibiotics, but their value for treating infections caused by several important Gram-negative pathogens becoming resistant to other antibiotics was realized in the mid-1990s. The lack of adequate pharmacokinetic and pharmacodynamic knowledge spurred the development of methods more specific for measuring polymyxin B and colistin after their administrations as sulphate salts, and of colistin and CMS after the administration of CMS sodium. These methods have been based on high-performance liquid chromatography, detection and quantification of fluorescent derivatives of the polymyxin bases, or of the bases themselves with detection and quantification by mass spectrometry.