LC and LC-MS/MS Studies for the Characterization of Forced Degradation Products of Tucatinib, a Novel Tyrosine Kinase Inhibitor

Abstract

The development, validation, and characterisation of forced degradation products utilising LC-MS/MS were the main goals of the current investigation.

Using an isocratic HPLC approach, tucatinib can be measured quantitatively at a wavelength of 239 nm in a simple, selective, validated, and well-defined manner. An isocratic elution of samples was performed on an Inertsil ODS (250x4.6mm, 5m) column with a mobile phase of 70:30v/v Acetonitrile and formic acid (0.1%) delivered at a flow rate of 1.0 mL/min. The degradation products created during the forced degradation investigation were characterised using MS/MS. 

Over the concentration range of 5-100\(\mu\)g/ml, a good linear response was obtained. Tucatinib's LOD and LOQ were determined to be 0.05 and 0.5, respectively. The approach was quantitatively assessed in terms of system appropriateness, linearity, precision, accuracy, and robustness in accordance with standard guidelines, and the findings were found to be within acceptable limits. In studies on forced deterioration, the medication decomposed in acidic, alkaline, and reduction environments. It was determined that the approach could be used for standard tucatinib analysis. Since there hasn't been any evidence of an LC-MS/MS method for quantifying tucatinib and its degradation products in the literature. A mechanism for researching the entire tucatinib degradation process has to be developed.