Development and validation of HPTLC method for estimation of dofetilide in pharmaceutical dosage form and determination of its degradation profile by MS-MS method

Abstract

Background: Dofetilide is the class III antiarrhythmic drug used as a potassium channel blocker approved by US FDA in 1999for the maintenance of sinus rhythm in individuals prone to atrial flutter and atrial fabrication. Currently there is no HPTLC-MSmethod reported for systematic characterization of degradation products dofetilide.Methods: As per the ICH guidelines, the HPTLC method for the determination of dofetilide both in bulk and pharmaceuticalformulation has been developed and validated. The degradation products were identified and characterized by using MS/MS.The Rf value was found to be 0.52±0.3. The degradation study was performed as per ICH guidelines (Q2R1). Isolation of thedegradation product by HPTLC method and categorized by MS/MS method.Results: The linearity of the method was found suitable over the range 100-600 ng/band with r2 of 0.998. Dofetilide wassubjected to stability studies, the drug was found to degrade under various stress conditions. The recovery was found in therange of 98-101%. HPTLC-MS/MS method showed a possible degradation mechanism of 7 degrading products. The degradation of the drug under various stress conditions indicates the storage conditions for the drug and drug product during itsshelf life.Conclusion: The HPTLC method developed for its linearity, range, precision studies, LOD and LOQ can be used for the routinequality control of the drug dofetilide in bulk drugs. The degradation pathway of a drug can help in the future to identify theimpurities and for the impurity profiling of dofetilide.