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Dicycloplatin is a new generation supramolecular platinum-containing anti-cancer drug. Due to its structure, it is difficult to differentiate dicycloplatin from physical mixtures of carboplatin and cyclobutane dicarboxylate, and confounding results may arise during drug characterization. To solve this problem, this study aims to provide a reliable and reproducible standard for the determination of dicycloplatin. A simple method for dicycloplatin quality control has been developed using X-ray powder diffraction (XRPD) and high performance liquid chromatography (HPLC). XRPD allowed the control of impurities and dissociation of the dicycloplatin active ingredient to less than 1%, and HPLC allowed the monitoring and control of the relative molar ratio of carboplatin and cyclobutane dicarboxylate within the purity range. The study proved for the first time that the dicycloplatin supramolecule is substantially different from a physical mixture of carboplatin and cyclobutane dicarboxylate.

A rapid and sensitive RP-HPLC method with UV detection for routine control of oxaliplatin in a pharmaceutical formulation (Eloxatin) was developed. Quantitation was accomplished with the internal standard method. The procedure was validated by linearity (correlation coefficient=0.999948), accuracy, robustness and intermediate precision. Experimental design was used during validation to calculate method robustness and intermediate precision. For robustness test three factors were considered: percentage v/v of acetonitrile, flow rate and temperature; an increase in the flow rate results in a decrease of the drug found concentration, while the percentage of organic modifier and temperature have no important effect on the response. For intermediate precision measure the considered variables were: analyst, equipment and days. The RSD value (2.27%, n=24) indicated a good precision of the analytical method.

Cis-dichloroamine (4-amino-2, 2, 6, 6-tetramethylpiperidine-1-oxyl) platinum (II) (abbreviated to HJ5) is a novel platinum anticancer compound which has prospects for research and application. In order to establish a conventional analytical method, an HPLC has been studied. Under the conditions of acetonitrile-water (10:90, volume ratio) as mobile phase, detection wavelength of 210 nm, a Phenomenex column C18(150 mm x 3.9 mm i.d., 10 microns). The linear equation, recovery and accuracy of the method were determined with external standard method. The HPLC has satisfactory resolution between the peaks of HJ5 and impurities. The peak areas of HJ5 were linear to its amounts detected and the detection limit was 0.07 microgram. The hydration of HJ5 can be inhibited effectively by NaCl solution. In a 9 g/L NaCl solution, the stability can be kept for more than 2 hours which is enough for analysis.

A sensitive postcolumn derivatization/UV detection system has been developed for HPLC analysis of antitumor divalent and quadrivalent platinum complexes. It is based on the derivatization of platinum complexes by reaction with sodium bisulfite to corresponding product(s) which has enhanced absorptivity at 280-300 nm. Platinum complexes examined in this study were cisplatin, carboplatin and oxaliplatin (divalent platinum complexes) and oxoplatin and tetraplatin (quadrivalent ones). The proposed detection system was sensitive to all these complexes. Under the detection conditions optimized for individual complexes, the HPLC gave linear relationships between the complex concentration and the peak height. Detection limits at 290 nm with 100 microliters injection were 20 nM for cisplatin, 40 nM for oxoplatin, 60 nM for carboplatin and tetraplatin and 100 nM for oxaliplatin (S/N = 3 at 0.005 AUFS). The proposed system was successfully applied for the determination of cisplatin and oxoplatin in plasma and urine. Pharmacokinetic behavior of oxoplatin and its reduced product cisplatin following a single intravenous injection of oxoplatin in rabbits has been discussed.