Abstract

The aim of the work is to present a simple LC-MS/MS approach for a sensitive, specific, and quantitative determination of Tucatinib in human K2EDTA plasma. Tucatinib is used in the treatment of metastatic HER2-positive breast cancer. Linearity and a high r2 value (>0.99) characterize the calibration curve, which spans 1–2,000 ng/ml. The quality control levels were executed with plasma blank to get 1, 3, 1,000, and 1,500 ng/ml for the lower limit of quantification, LQC,low quality control, MQC, and high quality control, respectively. The relative errors for the intra- and inter-batches were from 3.49% to 4.75% and 2.82% to 4.14%, correspondingly, with coefficient variation varying from −3.02% to 5.21% and 2.82% to 5.12%. During the retention period of Tucatinib and internal standard, there was no discernible interference from the endogenous peak. No matrix impact was seen in the test samples and was stable throughout the conditions exposed; moreover, recoveries were accurate across the whole calibration curve range. As per the USFDA bioanalytical technique validation guideline, the LC-MS/MS method was validated in terms of accuracy, linearity, precision, specificity, stability, dilution integrity, extraction recoveries, selectivity, and matrix effect. In conclusion, a new approach to evaluating Tucatinib in human K2EDTA plasma has been approved for use in clinical, bioavailability, and bioequivalence investigations, and it may be used to quantify Tucatinib.

Key words: Tucatinib, LC-MS/MS, K2EDTA plasma, Validation.