Determination of platinum-containing drugs in human plasma by liquid chromatography with reductive electrochemical detection

Abstract The platinum cis -diamminedichloroplatinum(II) (cisplatin or CDDP), which is used successfully to treat various kinds of tumour, can be determined in human plasma ultrafiltrate using liquid chromatography with reductive electrchemical detection (LC—ED). Polarographic analyses of other platinum-containing drugs have been carried out, and the results indicate that some of them might be good candidates for detection using the ED method. cis -Dichloro- trans -dihydroxo- cis -bis-(isopropylamine)platinum(IV) (CHIP or JM-9), diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDA or JM-8), and tetrachloro( trans -1,2-diaminocyclohexane)platinum(IV) (TCDCP), which are under evaluation for antitumour properties, have been investigated by this method. The results suggest that LC—ED may be a suitable technique for the determination of CHIP and TCDCP. The separation of cationic hydrolysis products from the neutral parent complex (CDDP) was carried out on reversed-phase columns, modified with alkylsuphonic acid ion-pair reagents. The rate of disapperance of CDDP in various media at 37.0°C was studied using this method. These results are in good agreement with those determined by other investigators using different methods. In addition, the monoaqua hydrolysis product was detected after incubation of CDDP with plasma ultrafiltrate and 100 m M sodium chloride. Atomic absorption spectrophotometry with electrothermal atomisation was used to determine the total platinum content in eluate fractions. This aided the identification of platinum-containing peaks in the LC—ED profile, and was also used to measure the percentage platinum recovered from the column.