Quantitative determination of Ecteinascidin 743 in human plasma by miniaturized high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
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.
Rosing
H
H
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Hillebrand
M J
MJ
Jimeno
J M
JM
Gómez
A
A
Floriano
P
P
Faircloth
G
G
Henrar
R E
RE
Vermorken
J B
JB
Cvitkovic
E
E
Bult
A
A
Beijnen
J H
JH
D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004149:Dioxoles / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007546:Isoquinolines / Q000097:blood* / Q000493:pharmacokinetics; D013058:Mass Spectrometry; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin
D000970:Antineoplastic Agents; D004149:Dioxoles; D007546:Isoquinolines; D012996:Solutions; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin