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Therapeutic monitoring of amphotericin B in Saudi ICU patients using UPLC MS/MS assay

Lookup NU author(s): Dr Bushra alQuadeib, Professor Lidija Siller, Dr Elaine Mutch, Dr Ben Horrocks, Professor Matthew Wright

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Abstract

Amphotericin B (AmB) is the first-line agent for the treatment of life-threatening invasive fungal infections. The aim of this study was to monitor AmB in critically ill Saudi patients in ICU after i.v. administration of 0.68 +/- 0.1 mg/kg/day Fungizone (R). A selective, sensitive and precise UPLC MS/MS method was developed to measure AmB concentrations in these patients. Seven ICU patients with creatinine clearance (ClCr) >40 mL/min were included. AmB levels were analyzed using a Waters Aquity UPLC MS/MS system, a BEH Shield RP18 column and detection via electrospray ionization source with positive ionization mode. The precision and accuracy of the developed UPLC method in the concentration range of 200-4000 ng/mL show no significant difference among inter- and-intra-day analysis (p > 0.05). Linearity was observed over the investigated range with correlation coefficient, r > 0.995 (n = 6/day). The pharmacokinetics of AmB in these patients, at steady state, showed a high terminal half-life of 124.6 +/- 73.4 h, with a highest concentration of 513.9 +/- 281.1 ng/mL, a lowest concentration 316.4 +/- 129.0 ng/mL and a mean clearance 91.1 +/- 39.2 mL/h/kg. The pharmacokinetics of AmB in critically ill Saudi patients in ICU was studied using a fully validated assay. A weak correlation (r = -0.22) of AmB Cl with ClCr was obtained, which suggests the need for further investigation in a larger population. Copyright (c) 2014 John Wiley & Sons, Ltd.


Publication metadata

Author(s): Al-Quadeib BT, Radwan MA, Siller L, Mutch E, Horrocks B, Wright M, Alshaer A

Publication type: Article

Publication status: Published

Journal: Biomedical Chromatography

Year: 2014

Volume: 28

Issue: 12

Pages: 1652-1659

Print publication date: 01/12/2014

Online publication date: 14/04/2014

Acceptance date: 07/03/2014

ISSN (print): 0269-3879

ISSN (electronic): 1099-0801

Publisher: John Wiley & Sons, Ltd.

URL: http://dx.doi.org/10.1002/bmc.3198

DOI: 10.1002/bmc.3198


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