Development and validation of a liquid chromatography-tandem mass spectrometry assay for the quantification of lurbinectedin in human plasma and urine

作者：van Andel L^*; Rosing H; Lubomirov R; Aviles P; Fudio S; Tibben M M^*; Nan Offering L; Schellens J H M; Beijnen J H

来源：Journal of Pharmaceutical and Biomedical Analysis, 2018, 158: 160-165.

DOI：10.1016/j.jpba.2018.05.053

• Lurbinectedin
• PM01183
• HPLC-MS/MS
• Plasma
• Urine
• Bioanalysis

Lurbinectedin is a novel highly selective inhibitor of RNA polymerase II triggering caspase-dependent apoptosis of cancerous cells. This article describes the development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to quantify lurbinectedin in human plasma and urine. Plasma samples were pre-treated with 1 M aqueous ammonia after which they were brought onto supported liquid extraction (SLE) columns. Lurbinectedin was eluted from the columns using tert-butyl methyl ether (TBME). Urine was first diluted in plasma and lurbinectedin was extracted from this matrix by liquid-liquid extraction using TBME. Samples were measured by LC-MS/MS in the positive electron ion spray mode. The method was linear over 0.1-100 ng/mL and 1-1000 ng/mL in plasma and urine, respectively, with accuracies and precisions within +/- 15% (20% for LLOQ) and below 15% (20% for LLOQ), respectively. The method was developed to support a mass balance study in which patients received a dose of 5 mg lurbinectedin.

• 出版日期2018-9-5