A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

Abstract

We describe a new high performance liquid chromatography coupled with ultraviolet detection method for the quantification of plasma concentration of oral iron chelating agent deferasirox. A simple protein precipitation extraction procedure was applied on 500 μl of plasma aliquots. Chromatographic separation was achieved on a C18 reverse phase column and eluate was monitored at 295 nm, with 8 min of analytical run. This method has been validated following Food and Drug Administration procedures: mean intra and inter day variability was 4.64 and 10.55%; mean accuracy was 6.27%; mean extraction recovery 91.66%. Calibration curves ranged from 0.078125 to 40 μg/ml. Limit of quantification was set at 0.15625 while limit of detection at 0.078125 μg/ml. We applied methodology developed on plasma samples of thalassaemic patients treated with deferasirox, finding correlation between deferasirox plasma concentrations and serum ferritin levels. This methodology allowed a specific, sensitive and reliable determination of deferasirox, that could be useful to perform its therapeutic monitoring and pharmacokinetic studies in patients plasma.

Deferasirox pharmacokinetic evaluation in β-thalassaemia paediatric patients†

“…The absence of significant correlation between DFX plasma AUC and drug dose confirms the high PK individual differences, as previously shown . An explanation of this event could be the involvement of genetic polymorphisms in genes encoding proteins able to metabolize and transport DFX, affecting its plasma exposure.…”

“…Calibration curves ranged from 0.078125 to 40 μg/ml. Limit of quantification (LOQ) was set at 0.15625 μg/ml while limit of detection (LOD) at 0.078125 μg/ml . The AUC over 24 h values were determined by the mixed log‐linear rule, using Kinetica software (Waltham, USA).…”

“…TDM consists in individualizing dosages with the aim of maximizing the efficacy of treatment minimizing toxicity, through an available assay that reliably measures the compound of interest. In 2012, De Francia et al, described and fully validated a new high performance liquid chromatography coupled with an ultraviolet detection method (HPLC‐UV) for the quantification of plasma DFX. Using this methodology, we focused on a paediatric population, and we described its pharmacokinetic (PK) parameters.…”

Simultaneous Determination of Plasma Deferasirox and Deferasirox-Iron Complex Using an HPLC-UV System and Pharmacokinetics of Deferasirox in Patients With β-Thalassemia Major: Once-daily Versus Twice-daily Administration

“…Both DEFR and Fe-(DEFR) 2 are primarily metabolized by glucuronidation, whereas elimination occurs by hepatobiliary excretion into the feces. 3,4 The initial pharmacokinetic (PK) profile of DEFR supported a once-daily dosing regimen because of its longer t ½ (11-19 hours) and the maintenance of DEFR plasma levels within the therapeutic range during a 24-hour period. 5 Interindividual differences were reported, particularly in patients who were prescribed a high dose of 40 mg/kg/d of DEFR.…”

Dried blood spot analysis of an iron chelator – Deferasirox and its potential application to therapeutic drug monitoring

“…HPLC-UV methods are available for the measurement of deferasirox [19,[26][27][28], deferasirox and iron complex [19,26] which requires lengthy run times and these methods suffer from selectivity related issues. Few LC-MS/MS methods are reported for the quantitation of deferasirox [19,[29][30][31], and its iron complex [19,29] using blood, urine or plasma as a matrix.…”