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

•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 1–1000 ng/mL ranges.•The assay was successfully applied for quantification of lurbinectedin in plasma and urine in a mass balance study....

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2018-09, Vol.158, p.160-165
Main Authors: van Andel, L., Rosing, H., Lubomirov, R., Avilés, P., Fudio, S., Tibben, M.M., Nan-Offeringa, L., Schellens, J.H.M., Beijnen, J.H.
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Language:English
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Summary:•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 1–1000 ng/mL ranges.•The assay was successfully applied for quantification of lurbinectedin in plasma and urine in a mass balance study. 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.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2018.05.053