Validated method for the determination of platinum from a liposomal source (SPI-77) in human plasma using graphite furnace Zeeman atomic absorption spectrometry.
A sensitive analytical method based on flameless atomic absorption spectrometry with Zeeman correction has been validated for the quantitative determination in human plasma of platinum originating from cisplatin in a liposomal source, SPI-77. The performance of the method was acceptable over a sample concentration range of 0. 125-1.25 micromol platinum/L and the lower limit of quantification was determined to be 1.25 micromol platinum/L in undiluted clinical samples. The performance data of the assay were investigated using both a calibration curve with carboplatin in plasma ultrafiltrate and diluted human plasma samples spiked with SPI-77. The recoveries, between-day and the within-day precisions of both methods of calibration were not significantly different allowing carboplatin ultrafiltrate calibration standards to be used to quantify platinum derived from SPI-77 in human plasma. Apparently, the liposomal formulation had no significant influence on the determination of platinum. The usefulness of the presented method was demonstrated in a phase I clinical and pharmacokinetic study. In addition, in vitro experiments were carried out to determine the distribution of SPI-77 in blood. The results indicated that platinum from SPI-77 mainly concentrates in plasma and that binding to and/or endocytosis in red blood cells is negligible.
The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam.
J M
JM
Meerum Terwogt
M M
MM
Tibben
H
H
Welbank
J H
JH
Schellens
J H
JH
Beijnen
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013054:Spectrophotometry, Atomic / Q000379:methods
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; C422270:SPI-77, liposomal; D002945:Cisplatin