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

Background: Dofetilide is the class III antiarrhythmic drug used as a potassium channel blocker approved by US FDA in 1999 for the maintenance of sinus rhythm in individuals prone to atrial flutter and atrial fabrication. Currently there is no HPTLC-MS method 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 pharmaceutical formulation 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 [+ or -] 0.3. The degradation study was performed as per ICH guidelines (Q2R1). Isolation of the degradation 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 [r.sup.2] of 0.998. Dofetilide was subjected to stability studies, the drug was found to degrade under various stress conditions. The recovery was found in the range 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 its shelf life. Conclusion: The HPTLC method developed for its linearity, range, precision studies, LOD and LOQ can be used for the routine quality control of the drug dofetilide in bulk drugs. The degradation pathway of a drug can help in the future to identify the impurities and for the impurity profiling of dofetilide. Keywords: Stability indicating, HPTLC, HPTLC-MS/MS degradation studies, dofetilide