title: Dried blood spot analysis of an iron chelator--deferasirox and its potential application to therapeutic drug monitoring.
abstract: 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 C(max) from DBS sample (1121 ng/mL) was comparable to mean C(max) found in blood samples (1015 ng/mL) at 2h after oral dose of deferasirox. All the other calculated pharmacokinetic parameters were quite comparable for both liquid blood and DBS samples.
authors.affiliation: Biopharmaceutical Research, Suven Life Sciences Ltd, Serene Chambers, Banjara Hills, Hyderabad, India. ramakrishna_nirogi@yahoo.co.in
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Nirogi
authors.forename: Devender Reddy
authors.initials: DR
authors.lastname: Ajjala
authors.forename: Vishwottam
authors.initials: V
authors.lastname: Kandikere
authors.forename: Raghupathi
authors.initials: R
authors.lastname: Aleti
authors.forename: SuryaRao
authors.initials: S
authors.lastname: Srikakolapu
authors.forename: Himabindu
authors.initials: H
authors.lastname: Vurimindi
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001565:Benzoates / Q000008:administration & dosage / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods; D000077588:Deferasirox; D059788:Dried Blood Spot Testing / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D005229:Fatty Acids, Monounsaturated; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000032:analysis*; D016014:Linear Models; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood*
chemical_list: D001565:Benzoates; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D007502:Iron Chelating Agents; D014230:Triazoles; D000077340:Fluvastatin; D000077588:Deferasirox