Development of an LC–ESI–MS/MS Method for the Quantification of Tucatinib in K2EDTA Human Plasma and Its Validation

ABSTRACT Aim of the work is to present a simple LC–ESI–MS/MS approach for a sensitive, specific, and quantitative determination of tucatinib in human K2EDTA plasma. During the retention period of tucatinib and internal standard erlotinib, there was no discernible interference from the endogenous peak. No matrix impact was seen in the test samples and was stable throughout conditions exposed; moreover, recoveries were accurate across the whole calibration curve range. As per the United States Food and Drug Administration 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. Linearity and a high r 2 value (>0.99) characterize the calibration curve, which spans 141.5–5660 ng/mL. The intra‐batch accuracy was within −8.45%–5.68% relative error and the precision was within 3.13%–4.91%. The inter‐batch accuracy was within −5.25%–4.64% relative error and the precision was within 3.34%–4.95%. 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.