Analysis of Ecteinascidin 743, a new potent marine-derived anticancer drug, in human plasma by high-performance liquid chromatography in combination with solid-phase extraction.
A reversed-phase high-performance liquid chromatographic method has been developed and validated for the quantification of the novel anticancer drug Ecteinascidin 743 in human plasma. The sample pretreatment of the plasma samples involved a solid-phase extraction (SPE) on cyano columns. Propyl-p-hydroxybenzoate was added after the sample pretreatment to correct for variability in injection volumes. The separation was performed on a Zorbax SB-C18 column (75x4.6 mm I.D., particle size 3.5 microm) with acetonitrile-25 mM phosphate buffer, pH 5.0 (70:30, v/v) as the mobile phase. The flow-rate was 1.0 ml/min and the eluent was monitored at 210 nm. The accuracies and precisions of the assay fall within +/-15% for all quality control samples and within +/-20% for the lower limit of quantitation, which was 1.0 ng/ml using 500 microl of plasma. The overall recovery of the sample pretreatment procedure for Ecteinascidin 743 was 87.0+/-5.9%. The drug was found to be stable in human plasma at -30 degrees C for at least 2 months. At room temperature Ecteinascidin 743 was stable in human plasma for 5 h at most.
Dept. of Pharmacy and Pharmacology, Slotervaart Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands.
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H
Rosing
M J
MJ
Hillebrand
J M
JM
Jimeno
A
A
Gómez
P
P
Floriano
G
G
Faircloth
L
L
Cameron
R E
RE
Henrar
J B
JB
Vermorken
A
A
Bult
J H
JH
Beijnen
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004149:Dioxoles / Q000097:blood* / Q000493:pharmacokinetics; D005069:Evaluation Studies as Topic; D006801:Humans; D007546:Isoquinolines / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D014561:Urochordata
D000970:Antineoplastic Agents; D004149:Dioxoles; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin