Abstract

HILIC-MS/MS FOR TRABECTEDIN QUANTIFICATION: OVERCOMING PHARMACOKINETIC CHALLENGES IN CANCER THERAPY

P. S. Seethal*, S. Risana Nizar and S. Sunwin

.

Abstract

Objective: To develop a sensitive, high-throughput HILIC-MS/MS method for measuring trabectedin in human plasma. This method addresses the issues of current LC-MS/MS techniques, such as lengthy SPE steps and large sample sizes. Methods: We used protein precipitation with acidified acetonitrile (0.1% formic acid). This was followed by HILIC separation on an Acquity BEH Amide column (2.1 × 100 mm, 1.7 μm) and MRM detection (*m/z* 762→234 for trabectedin and *m/z* 765→234 for d3-trabectedin internal standard). Validation included checking linearity (0.01–2.5 ng/mL), precision (80%), and matrix effects. Results: The method achieved a limit of quantification of 0.01 ng/mL with a 7- minute runtime. When applied to 26 STS patients receiving a 1.5 mg/m² dose of trabectedin (24-hour infusion), it showed a median AUC0–48h of 33.28 μg·h·L⁻¹ and a Cmax of 1.8 μg/L.

Keywords: Trabectedin, HILIC-MS/MS, Soft Tissue Sarcoma, LC-MS, Pharmacokinetics, Bioanalytical Method.