T3227: Therapeutic Monitoring of Amphotericin B in Saudi ICU Patients Using UPLC MS/MS Assay -
alQuadeib, Bushra . 2013
Purpose: Monitoring of amphotericin-B (AmB) in Saudi critically ill patients in ICU after IV administration of 0.5-0.75 mg/kg/day AmB as Fungizone. Developing a fast, robust, selective, sensitive, and precise UPLC MS/MS method, to study the pharmacokinetics of AmB in these patients.
Methods; Waters AQUITY UPLC MS/MS system was used. After protein precipitation, the separation was performed on UPLCTM BEH Shield RP18 column with an gradient elution,and the detection was via electrospray ionization source with positive ionization mode, at 925.2 -> 742.3 and 321.8 -> 155 m/z for AmB and Clopidogrel (IS), respectively. Noncompartmental model was used to calculate the pharmacokinetics of AmB in these patients.
Results: A fast, robust, selective, sensitive, and precise UPLC MS/MS method for the monitoring of AmB in human plasma using clopidogrel as IS was developed. The method was validated by estimating the precision and accuracy for inter- and-intra-day analysis in the concentration range of 200-2000 ng/ml. The method was liner over the investigated range with all the correlation coefficient, r > 0.995 in six replicates. The intra- and-inter-day precision (9.6 to 17.6%), and the inaccuracy (8.0 to 14.1%) . The assay run time was 3.2 min. The pharmacokinetics of AmB in these patients showed a Cmax of 456.5 +/- 250.3 ng/ml, Cmin 316.4+/-128.9 ng/ml, t1/2 125.6+/-72.7 h, Cl 86 +/- 39 ml/h/kg at steady state condition. There was an excellent correlation (0.93) between the AmB clearance and creatinine clearance in these patients, which was not reported before.
Conclusion: This rapid and sensitive method was validated and could be applied to pharmacokinetics studies for the determination of AmB concentrations in human plasma samples. It is recommended to calculate AmB dose based on creatinine clearance in critically ill ICU patients.
Purpose: Monitoring of amphotericin-B (AmB) in Saudi critically ill patients in ICU after IV administration of 0.5-0.75 mg/kg/day AmB as Fungizone. Developing a fast, robust,…
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…