Analytical methodologies for measuring colistin levels in pharmacokinetic studies

Colistin is an old antibiotic reintroduced in response to an increased incidence of multi-resistant Gram-negative bacterial infections. It has a narrow therapeutic window, and dose optimization is required. Dose optimization requires accurate method of measurement. The goal of this manuscript is to review previously developed methods, their advantages and disadvantages, and problems to be addressed for colistin assay in pharmacokinetic studies. Articles published in English from December 2000 to 2019 were systematically searched using PubMed and Scopus. Reference lists of articles were reviewed to identify additional studies. A total of 220 articles were identified, 26 of which met the inclusion criteria in this review. Of those, six articles were found to contain relevant methods for pharmacokinetic analysis of colistin in subjects treated with colistimethate sodium. The report describes sample preparation techniques, analytical methods used for the determination, and quantification of colistimethate sodium and colistin, mobile phase use, and problems encountered. One of the greatest challenges in colistin bioanalysis is ensuring the stability of colistimethate sodium in vivo and in vitro prior analysis. This review also highlights the precautionary measures to minimize hydrolysis of colistimethate sodium during experiments.