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

Autor: Rosing H; Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands., Hillebrand MJ, Jimeno JM, Gómez A, Floriano P, Faircloth G, Henrar RE, Vermorken JB, Cvitkovic E, Bult A, Beijnen JH
Jazyk: angličtina
Zdroj: Journal of mass spectrometry : JMS [J Mass Spectrom] 1998 Nov; Vol. 33 (11), pp. 1134-40.
DOI: 10.1002/(SICI)1096-9888(1998110)33:11<1134::AID-JMS730>3.0.CO;2-S
Abstrakt: 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 microgram 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 microliters 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.
Databáze: MEDLINE