An Application Of Forced Degradation Studies Of Tipiracil With A Developed And Validated RP-HPLC Method As Per ICH Guidelines
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Abstract
Tipiracil is a thymidine phosphorylase (TPase) inhibitor. Its function prevents the breakdown of the active component of trifluridine, thus increasing the bioavailability of trifluridine and boosting its systemic presence. The drug was subjected to forced degradation studies as per the conditions prescribed in ICH Q1 (R2) guideline. Tipiracil degraded in hydrolytic (acid and alkaline) and oxidative stress conditions. The drug was found to be stable in thermal and photolytic conditions. The novel degradation products were obtained and were well separated using an HPLC C18 stationary phase Cosmosil (250 × 4.6 mm, 5 μm) and mobile phase composed of Phosphate buffer (pH 3.0): Acetonitrile (30:70) pumped at 1.0 mL min−1 flow rate. The column temperature was set at 25°C and the detection at 257 nm using DAD detector. All the degradation products were isolated and characterised. A well resolved chromatographic method proposed in this study suggests that the proposed analytical method finds its application as a stability indicating assay method for the drug and can be used in routine analysis. The developed HPLC method will also suffice the suitability for impurity profiling and assay of Tipiracil in bulk drugs and pharmaceutical formulations.
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References
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