Abstract
Colistin is a polymixin antibiotic (polymixin E) that is produced by Bacillus colistinus bacteria. The aim of the present study was to develop and validate a method to quantify colistin levels in plasma using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique and then apply it in experimental animals (rats) to investigate the pharmacokinetic profile of colistin in this species. Polymyxin B was used as an internal standard (IS) and the quantitation was carried out using ESI + interface and employing multiple reaction monitoring (MRM) mode. A mobile phase consisting of acetonitrile:water:formic acid (30:70:0.1%; v/v/v) was employed and Zorbax eclipse plus C18 (1.8 µm, 2.1 mm i.d. x 50 mm) was the optimal column for this method and utilized at a flow rate of 0.2 mL/min. The full scan mass spectra of precursor/product ions of colistin A were at m/z 585.5 > 100.8, for colistin B at m/z 578.8 > 101 and for the IS at m/z 602.8 > 101. The lower limit of quantification (LLOQ) was 0.5 µg/mL. The method demonstrated acceptable intra-run and inter-run precision and accuracy for both colistin A and colistin B. Colistin was stable when assessed for long-term stability, freeze-thaw stability and autosampler stability. However, it was not stable when stored at room temperature. The matrix effect evaluation showed minimal or no effect. Incurred sample reanalysis findings were within acceptable ranges (<20% of the nominal concentration). The pharmacokinetic parameters of colistin were investigated in rats using the present method. The developed method for colistin demonstrates that it is rapid, sensitive, specific, accurate, precise, and reliable.
Highlights
Resistance to antibiotics is an ongoing concern of the medical and pharmaceutical industries
It has been reported that the inhalation of colistin sulphate in cystic fibrosis (CF) patients resulted in a maximum serum concentration of 0.13 mg/L after 1.5 h21
A mobile phase consisting of 30% (v/v) acetonitrile, 70% (v/v) water and 0.1% (v/v) formic acid was selected as the optimal mobile phase since it gave better formation of precursors and product ions than other compositions attempted
Summary
Resistance to antibiotics is an ongoing concern of the medical and pharmaceutical industries. Cases of chronic pulmonary infections with Pseudomonas aeruginosa (P. aeruginosa) are an immense challenge to health care professionals when dealing with cystic fibrosis (CF) patients[3]. The increase in the number of cases infected with multi-drug resistant (MDR) Gram-negative bacteria has led to the re-use of polymixin antibiotics[5]. These MDR Gram-negative bacteria are often of the following species: P. aeruginosa, Acinetobacter baumannii (A. baumannii) and Klebsiella pneumoniae (K. pneumoniae) which developed strains that are mostly susceptible only to polymixins[6,7,8]. The renal route is the main elimination pathway of CMS and it has a t1/2 of 124 ± 52 min in CF patients[26] in contrast to colistin which is eliminated extra-renally and its elimination half-life (3 h) is longer than that of CMS27
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