Quantitative determination of Ecteinascidin 743 in human plasma by miniaturized high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

✍ Scribed by Rosing, H.; Hillebrand, M. J. X.; Jimeno, J. M.; Gómez, A.; Floriano, P.; Faircloth, G.; Henrar, R. E. C.; Vermorken, J. B.; Cvitkovic, E.; Bult, A.; Beijnen, J. H.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 124 KB
• Volume: 33
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/(sici)1096-9888(1998110)33:11<1134::aid-jms730>3.0.co;2-s

✦ Synopsis

A method was developed for the bio-analysis of Ecteinascidin 743 (ET-743) using miniaturized liquid chromatography (LC) coupled to an electrospray ionization sample inlet (TurbolonSpray) and two quadrupole mass analyzers (LC/ESI-MS/MS). Solid-phase extraction was used as a sample pretreatment procedure. Ecteinascidin 743 is a very potent anticancer compound and is administered in lg m-2 dosages, which demands special requirements in terms of sensitivity for the analytical method supporting clinical pharmacokinetic studies. Using conventional LC/UV, a lower limit of quantitation (LLQ) of 1 ng ml-1 plasma was reached using a 500 ll sample volume, but LC/ESI-MS/MS permitted an LLQ of 10 pg ml-1. The latter method was found to be accurate and precise, and provided a broad linear concentration range of 0.010-2.50 ng ml-1.