A more sensitive MS detector does not obviously lead to a more sensitive assay: experiences with ES-285.
In this paper the transfer of an existing method for the quantitative determination of the anticancer agent ES-285 in human plasma using liquid chromatography tandem mass spectrometry on an API 365 to an API 3000 mass spectrometer is described. The transfer appeared not to be straightforward. Problems arose resulting from carry-over and interferences. In addition, due to the expansion of the calibration range, data ought to be weighted with a different factor to increase the accuracy of the lower concentrations. After finding appropriate solutions for these problems, the lower limit of quantitation could be lowered from 10 to 1 ng/mL for ES-285 in human plasma. The usefulness and necessity of the modified assay was demonstrated by analysis of plasma samples from a patient receiving a low dosage of the drug.
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. apess@slz.nl
Ellen
E
Stokvis
Hilde
H
Rosing
Luis
L
López-Lázaro
Jan H M
JH
Schellens
Jos H
JH
Beijnen
D000473:Alkanes / Q000097:blood* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000493:pharmacokinetics; D013058:Mass Spectrometry / Q000295:instrumentation*; D012680:Sensitivity and Specificity
D000473:Alkanes; D000970:Antineoplastic Agents; D008055:Lipids; C408363:spisulosine