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Metallo-DrugsPlatinum Based Cancer Therapeutics Validated methods for platinum assays using ICPMS have been established at the low to sub ng/mL levels for three matrices of clinical interest: urine, plasma and plasma ultrafiltrate. Methods have been developed using LC-ICPMS to speciate the various “free” equilibria and degradation products of the two widely used platinum based cancer therapeutics: carboplatin and cisplatin. A quantitative and specific assay for free carboplatin using extraction or ultrafiltration with LC-ICPMS has been validated; allowing a more sensitive, specific and direct alternative to the conventional ultrafiltration/ LC-UV approach. Metal Speciation Since early 2000, CANTEST has been developing an increasing array of metal speciation assays based on LC-ICPMS. The methods are amenable to a variety of separation options including ion exchange chromatography, reverse phase chromatography and weak anion exchange/ size exclusion chromatography. The simplest applications of this technique enable the separation of various cationic and anionic species of a given element with different valences and toxicities. Detection limits for these assays typically meet or exceed regulatory limits/ guidelines in water, foods and biota. LC-ICPMS also allows for specific quantitation of metallo-drugs (carboplatin or cisplatin) in biological matrices such as plasma, plasma ultrafiltrate and urine. More recently, chromatography coupled ICPMS has been used to evaluate the protein binding and bioavailability of metallo-drugs, essential elements and heavy metals. Select protein groups such as transferrins, albumins and metallothioneins may be tracked via endogenous elemental markers while being simultaneously monitored for toxic impurities. |
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