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

Deferasirox is an iron chelating agent for the treatment of transfusional iron over load in patients with chronic anemia. These anemic patients require close monitoring of the deferasirox exposures for ensuring its therapeutic efficacy. Dried blood spot (DBS) sampling methodology has the advantages of low volume of blood withdrawal and ease of transportation and storage over liquid blood methods. A LC–MS/MS based analytical method was developed using reversed phase column with gradient elution program and quantitated in MRM mode. Linearity range for the liquid blood was 1–1000 ng/mL and for DBS was 5–5000 ng/mL under similar mass spectrometry conditions. The method was validated with respective (M−H)− ions, m/z 372→118 for deferasirox and m/z 410→348 for fluvastatin (internal standard). The validated method was applied for the analysis of DBS samples from a rat pharmacokinetic study and results were compared against liquid blood samples from the same animal. The mean Cmax from DBS sample (1121 ng/mL) was comparable to mean Cmax found in blood samples (1015 ng/mL) at 2 h after oral dose of deferasirox. All the other calculated pharmacokinetic parameters were quite comparable for both liquid blood and DBS samples.

► Deferasirox is an iron-chelator used in treating the transfusional iron overload.
► Therapeutic drug monitoring of deferasirox was required to titrate dosage for its efficacy/toxicity.
► Quantification of deferasirox was performed by LC–MS/MS using dried blood spot (DBS) approach.
► Pharmacokinetic parameters obtained in DBS method were compared with that of the whole blood method.
► Feasibility to translate method developed in rat DBS to human DBS was checked.
► Fragmentation pathway of deferasirox was described similar to 1,2,4-Triazoles.