Abstract
<p class="Default"><strong>Objective: </strong>A simple, cost-effective and mass compatible ultra-high fast performance liquid chromatographic (Agilent-Infinity LC 1290) method has been developed and validated for the determination of potentially genotoxic impurities in dasatinib active pharmaceutical ingredients.</p><p class="Default"><strong>Methods: </strong>This method comprises the determination of three possible genotoxic impurities in dasatinib. The mobile phase is trifluoroacetic acid, acetonitrile and water with linear gradient elution curve number 6. The column used for the development and validation is zorbax RRHD eclipse plus C18 with the length of 50 mm, the internal diameter of 2.1 mm and particle size of 1.8 microns.</p><p class="Default"><strong>Results: </strong>The limit of detection of the potential genotoxic impurities are less than 0.1 µg/ml with respect to dasatinib test concentration of 1000 µg/ml. The limit of quantification of the potential genotoxic impurities is less than 0.3 µg/ml with respect to dasatinib test concentration of 1000 µg/ml.</p><p style="margin: 6pt 0cm; text-align: justify;"><strong>Conclusion: </strong>This method has been validated as per ICH guidelines Q2 (R1). These three potential mutagenic impurities are not degradant impurities of dasatinib and its only process related impurities. The method development has been approached using the QbD principle.</p>
Highlights
Sprycel is indicated for the treatment of adults with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase
Dilute 1 ml of trifluoroacetic acid in 1000 ml of HPLC grade water used as mobile phase-D1 and dilute 1 ml of ammonium hydroxide in 1000 ml of HPLC grade water used as mobile phase-D2
The resolution between the peaks was observed that more than resolution of 1.5. These results showed that the system was suitable and accepted for the determination of imp-1, imp-2 and imp-3 in dasatinib drug substance at the level of potentially genotoxic impurities
Summary
Sprycel (dasatinib) is indicated for the treatment of adults with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness is based on cytogenetic response and major molecular response rates. The trial is ongoing, and further data will be required to determine longterm outcome. Chronic, accelerated, or myeloid or lymphoid blast phase Ph+CML with resistance or intolerance to prior therapy including imatinib. Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with resistance or intolerance to prior therapy. The recommended starting dosage of sprycel for chronic phase CML is 100 mg administered orally once daily
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