Determination of total platinum in plasma and plasma ultrafiltrate, from subjects dosed with the platinum-containing N-(2-hydroxypropyl)methacrylamide copolymer AP5280, by use of graphite-furnace Zeeman atomic-absorption spectrometry.
AP5280 is an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer to which are linked tetrapeptide side chains containing bioactive platinum complexes at their C-terminal sides. We have developed and validated a rapid and sensitive analytical assay for the determination of total platinum concentrations in plasma, and free platinum of an AP5280 origin in plasma ultrafiltrate (PUF), of subjects dosed with AP5280. The total platinum levels were determined by use of graphite-furnace atomic-absorption spectrometry (GF-AAS) with Zeeman correction after appropriate dilution of the plasma sample with plasma-hydrochloric acid 0.2 mol L(-1) (1:5) as diluent. The limit of quantitation of this assay is 0.25 micromol L(-1) platinum in plasma. Linear calibration curves were obtained over the concentration range 0.25-5.0 micromol L(-1). Accuracy was between 87.7% and 104.2% and precision was 15.3% at the lowest concentration and less than 14% for all other levels tested. Accuracy and precision were thus in accordance with generally accepted criteria for analytical methods. Analysis of samples obtained from patients receiving AP5280 demonstrated the applicability of the described assay. Analysis of free platinum in PUF was performed by use of a previously validated and reported assay from our institute in which the same instrumental method is used.
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. apmtb@slz.nl
M M
MM
Tibben
J M
JM
Rademaker-Lakhai
J R
JR
Rice
D R
DR
Stewart
J H M
JH
Schellens
J H
JH
Beijnen
D000178:Acrylamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002138:Calibration; D016503:Drug Delivery Systems / Q000592:standards; D006440:Hemofiltration; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010984:Platinum / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013054:Spectrophotometry, Atomic
D000178:Acrylamides; C438846:HPMA copolymer-platinate; D009944:Organoplatinum Compounds; D010984:Platinum