Zepsyre ( PM1183 ) . Development and validation of a liquid chromatography-tandem mass spectrometry assay for the quantification of lurbinectedin in human plasma and urine .

Journal of Pharmaceutical and Biomedical Analysis.
Available online 1 June 2018.

Lvan Andela , H. Rosinga, R. Lubomirov, P. Avilés, S. Fudio, M.M. Tibbena, L. Nan-Offeringa, J.H.M. Schellens , J.H. Beijnena .

Highlights

• A rapid and sensitive LC-MS/MS method developed to quantify lurbinectedin in human plasma and urine.

• The assay has successfully been validated in the 0.1–100 and 1–1,000 ng/mL ranges .

• The assay was successfully applied for quantification of lurbinectedin in plasma and urine in a mass balance study .

Abstract

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.