Simple and sensitive liquid chromatographic quantitative analysis of the novel marine anticancer drug Yondelis™ (ET-743, trabectedin) in human plasma using column switching and tandem mass spectrometric detection

✍ Scribed by E. Stokvis; H. Rosing; L. López-Lázaro; J. H. Beijnen

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 146 KB
• Volume: 39
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.608

✦ Synopsis

Abstract

The development of a simple and sensitive assay for the quantitative analysis of the marine anticancer agent Yondelis (ET‐743, trabectedin) in human plasma using liquid chromatography (LC) with column switching and tandem mass spectrometric (MS/MS) detection is described. After protein precipitation with methanol, diluted extracts were injected on to a small LC column (10 × 3.0 mm i.d.) for on‐line concentration and further clean‐up of the sample. Next, the analyte and deuterated internal standard were back‐flushed on to an analytical column for separation and subsequent detection in an API 2000 triple‐quadrupole mass spectrometer. The lower limit of quantitation was 0.05 ng mL^−1^ using 100 µl of plasma with a linear dynamic range up to 2.5 ng ml^−1^. Validation of the method was performed according to the most recent FDA guidelines for bioanalytical method validation. The time needed for off‐line sample preparation has been reduced 10‐fold compared with an existing LC/MS/MS method for ET‐743 in human plasma, employing a labor‐intensive solid‐phase extraction procedure for sample pretreatment. The proposed column switching method was successfully applied in phase II clinical trials with Yondelis and pharmacokinetic monitoring. Copyright © 2004 John Wiley & Sons, Ltd.