Development, Validation, and Application of an LC–MS/MS Method for Pharmacokinetic Studies for the Datopotamab Deruxtecan-Dlnk Quantification in Rat Plasma

Abstract

To quantify datopotamab deruxtecan-dlnk in rat plasma, a selective, sensitive, and quick LC–MS/MS technique was created, validated, and successfully used in pharmacokinetic investigations. The analyte separation was accomplished on an Agilent Eclipse XDB-C18 analytical column (150 × 4.6 mm, 3.5 μm particle size) employing isocratic elution using an acetonitrile and buffer mobile phase (50:50, v/v) delivered at 1.0 mL/min. The internal standard was tisotumab vedotin. Mass spectrometric analysis was conducted using electrospray ionization (ESI) operated in the multiple reaction monitoring (MRM) mode. A simple and efficient protein precipitation technique was employed to prepare the sample. The method demonstrated remarkable linearity within the range of 25–1000 ng/mL, with an r² value exceeding 0.999. Accuracy values ranged between 93.76% and 106.23%, with corresponding intraday and interday precision values being within reasonable bounds. There were no discernible matrix effects, and recovery was reliable and repeatable. Datopotamab deruxtecan-dlnk was found to be stable under all tested conditions, according to stability studies. After intravenous injection, the validated approach was effectively applied to pharmacokinetic research in rats, allowing for accurate estimates of important pharmacokinetic parameters. This approach is ideal for routine bioanalysis and pharmacokinetic evaluation of datopotamab deruxtecan-dlnk in preclinical research.