title: Therapeutic monitoring of amphotericin B in Saudi ICU patients using UPLC MS/MS assay.
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®. 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.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Bushra T
authors.initials: BT
authors.lastname: Al-Quadeib
authors.forename: Mahasen A
authors.initials: MA
authors.lastname: Radwan
authors.forename: Lidija
authors.initials: L
authors.lastname: Siller
authors.forename: Elaine
authors.initials: E
authors.lastname: Mutch
authors.forename: Ben
authors.initials: B
authors.lastname: Horrocks
authors.forename: Matthew
authors.initials: M
authors.lastname: Wright
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Alshaer
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003430:Cross-Sectional Studies; D004355:Drug Stability; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012529:Saudi Arabia; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000666:Amphotericin B
keywords: Fungizone®; UPLC MS/MS; amphotericin B; human; pharmacokinetics