Sequential extraction of platinum, cisplatin and carboplatin from environmental samples and pre-concentration/separation using vesicular coacervative extraction and determination by continuum source ETAAS.

A sequential extraction procedure is developed for the separation of trace levels of hexachloroplatinate, cisplatin and carboplatin from soil, which are then, pre-concentrated using a vesicular coacervative cloud point extraction method prior to their determination as platinum by continuum source ETAAS. Sequential extraction of carboplatin, cisplatin and hexachloroplatinate from a specific red soil is achieved by using the 20% HCl, aqua regia at room temperature and by combination of aqua regia and HF with microwave digestion, respectively. The pre-concentration of these species from the extracted solutions is based on the formation of extractable hydrophobic complexes of PtCl6(2-) anionic species with free cationic head groups solubilizing sites of the Triton X-114 co-surfactant stabilized TOMAC (tri-octyl methyl ammonium chloride) vesicles through electrostatic attraction. This process separates the platinum from bulk aqueous solution into a small vesicular rich phase. The parameters affecting the extraction procedures are optimized. Under the optimized conditions, the achieved pre-concentration factor is 20 and detection limit is 0.5 ng g(-1) for soil and 0.02 ng mL(-1) for water samples. The spiked recoveries of hexachloroplatinate, cisplatin and carboplatin in water and soil extracts in the vesicular coacervative extraction are in the range of 96-102% at 0.5-1 ng mL(-1) with relative standard deviation of 1-3%. The accuracy of the method for platinum determination is evaluated by analyzing CCRMP PTC-1a copper-nickel sulfide concentrate and BCR 723 road dust certified reference materials and the obtained results agreed with the certified values with 95% confidence level of student t-test. The results were also compared to mixed-micelle (MM)-CPE method reported in the literature.

Quantification of intact carboplatin in human plasma ultrafitrates using hydrophilic interaction liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

Carboplatin is a platinum agent that is used for treatment of non-small-cell lung cancer and ovarian cancer. A sensitive and selective analytical method for the quantification of carboplatin in human plasma ultrafiltrates using liquid chromatography-tandem mass spectrometry was developed. Human plasma ultrafiltrates were precipitated by acetonitrile containing carboplatin-d4 as an internal standard and were further diluted with acetonitrile. Chromatographic separation was performed on a Accucore HILIC (50mm×2.1mm i.d., 2.6µm) column using mobile phase (acetonitrile-water-acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min. Detection was performed on electrospray ionization triple quadrupole tandem mass spectrometer using low-energy collision induced dissociation (CID-MS/MS) analysis operating in the selected reaction monitoring (SRM) scan mode. The lower limit of quantification for carboplatin was 0.025µg/mL. This method covered a linearity range of 0.025-50µg/mL. The intra-day precision and inter-day precision (R.S.D.) ranged from 1.5 to 4.3%, and the accuracy (R.E.) was within ±2.9%. The present method was applied to a clinical pharmacokinetic study of carboplatin in a cancer patient.

HPLC method for the determination of carboplatin and paclitaxel with cremophorEL in an amphiphilic polymer matrix.

Simple and rapid reversed phase HPLC methods for individual as well as simultaneous analysis of paclitaxel and carboplatin with cremophorEL (CrEL) in an amphiphilic polymer matrix were developed. Different analytical performance parameters such as linearity, accuracy, precision, specificity, limit of detection (LOD) and limit of quantification (LOQ) were determined according to ICH guidelines. All the analytical methods were developed by reverse phase HPLC on C-18 column with a mobile phase comprising of water-acetonitrile run on isocratic mode for the analysis of carboplatin and gradient mode for individual analysis of paclitaxel and for simultaneous analysis of the two drugs at a flow rate of 1 ml/min at 227 nm. The proposed methods for independent analysis of the drugs elute out carboplatin in 4.3 min and paclitaxel in 10.5 min while in simultaneous analysis carboplatin shows R(t) at 4 min and paclitaxel at 18 min with a continuous run for 17 more minutes to elute out CrEL. These methods were found to be specific as none of the components of the media, i.e. polymer, CrEL and buffer interfered with the drug peaks. The linearity of the calibration curves for each analyte in the desired concentration range was found to be good (r(2)>0.9995). The methods were accurate and precise with recoveries ranging from 98 to 101% for each drug and relative standard deviation (%RSD) <2%. Peaks corresponding to each of the drug showed positive value for the minimum peak purity index over the entire range of integrated chromatographic peak thus indicating the purity of the peaks. Stability analysis of the two drugs revealed that the drugs remain stable during the period of study.