Trace analysis of SN-38 in human plasma by high-performance liquid chromatography.
A reversed-phase high-performance liquid chromatographic method with fluorescence detection was developed and validated for the quantitation of SN-38, the active metabolite of irinotecan (CPT-11), a new anticancer drug. This method uses solid-phase extraction with a C18 column for sample clean-up and concentration following acidification of human plasma with two volumes of 0.1 M HCl. Using blank plasma spiked with SN-38, we found the assay to be linear over the concentration range of 10-500 pM (3.9-195 pg/ml) with acceptable total and within-day imprecision. The recovery of SN-38 ranged from 48.3% (10 pM) to 91.5% (500 pM) whereas that of the internal standard, 20-(S)-camptothecin, was 96.9% (500 pM). This method represents a sizeable increase in sensitivity over other published methods and is shown to be suitable for the measurement of 'trough' concentrations of SN-38 during the treatment of patients with a weekly regimen of irinotecan.
Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
L P
LP
Rivory
M
M
Findlay
S
S
Clarke
J
J
Bishop
D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D000077146:Irinotecan; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin