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Investigation of unbound colistin A and B in clinical samples using a mass spectrometry method

Fage, D., Deprez, G., Wolff, F., Hites, M., Jacobs, F., Van Bambeke, F., Cotton, F.
International journal of antimicrobial agents 2019 v.53 no.3 pp. 330-336
albumins, colistin, creatinine, drugs, glycoproteins, mass spectrometry, monitoring, patients, protein content, therapeutics, ultracentrifugation, ultrafiltration
Colistin, used as a last-resort drug, has a narrow therapeutic range that justifies therapeutic drug monitoring. Few data are available in the literature regarding the in vivo unbound fraction of colistin. The objectives of this study were to develop a method to isolate unbound colistin in clinical samples by ultrafiltration and to quantify it. The association between unbound colistin and biological parameters (total protein, albumin, alpha-1-acid glycoprotein and creatinine) was investigated. The measured ranges were 0.036–7.160 mg/L for colistin A and 0.064–9.630 mg/L for colistin B. The process of isolation and determination of unbound colistin was applied to clinical samples (n = 30) within 40 min and no non-specific binding was observed during the ultracentrifugation step. The median unbound fractions of colistin measured were 34.3% (12.8–51.0%) and 53.4% (27.0–77.8%) for colistin A and B, respectively. High interindividual biological variation of binding was observed for colistin A and B that was not explained by the biochemical parameters studied. The method developed could be useful to improve outcomes for patients.