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Characterization of imatinib mesylate formulations distributed in South American countries: Determination of genotoxic impurities by UHPLC–MS/MS and dissolution profile
Author(s) -
Wolff Fernanda Caroline,
Dillenburg Thaís Luise,
Venzon Antunes Marina,
Linden Rafael,
Comparsi Wagner Sandrine,
Verza Simone G.
Publication year - 2018
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4222
Subject(s) - chemistry , chromatography , ammonium formate , formic acid , dissolution , imatinib mesylate , drug , dissolution testing , analyte , pharmacology , imatinib , organic chemistry , medicine , myeloid leukemia , immunology , biopharmaceutics classification system , biology
Imatinib mesylate (IM) is an anti‐neoplasic drug used for the treatment of cancer. Recent new guidelines specify daily doses and concentration limits for genotoxic impurities (GTIs) in pharmaceutical final products. Therefore, in this work an analytical method using UHPLC–MS/MS was developed, validated and applied to characterize IM tablets for two GTIs: N‐ (2‐methyl‐5‐aminophenyl)‐4‐(3‐pyridyl)‐2‐pyrimidine amine (Imp. 1), and N‐ [4‐methyl‐3‐(4‐methyl‐3‐yl‐pyrimidin‐2‐ylamino)‐phenyl]‐4‐ chloromethyl benzamide (Imp. 2), simultaneously. Additionally, dissolution data of IM tablets were compared using a methodology recommended by the US Food and Drug Administration. The UHPLC method utilized an Acquity BEH C 18 (150 × 2.1 mm, 1.7 μm) maintained at 40°C. The mobile phase consisted of ammonium formate 0.063% (phase A) and acetonitrile plus 0.05% formic acid (phase B) in gradient elution. A sensitive method for determination of previously mentioned GTIs in IM tablets was successfully developed and applied. Overall, the formulations analyzed in this work showed low levels of Imp. 1 and Imp. 2. However, the sample named D1 showed very high levels of Imp. 1 and failed to meet the requirements established by the US Food and Drug Administration for dissolution data. Periodic verification of GTIs in pharmaceutical formulations is important to minimize safety risks, so analytical methods to determine it need be available and implemented in routine analysis.