Significant inter-patient variations in pharmacokinetics and pharmacodynamics have been associated with anticancer drugs, which generally have narrow therapeutic index.Reliable and practical bioanalytical methods are required for measuring drug concentrations in various biological fluids in order to understand preclinical and clinical pharmacology, and new drug development.In this regard, HPLC-based technology gains rapid expansion in recent years due to its versatility, sensitivity and robustness, such as inductively coupled plasma mass spectrometry (ICP-MS).Platinum-based anticancer drugs are one of the most important classes of chemotherapeutic agents in the treatment of testicular, ovarian, breast, lung, esophageal and gastric cancers.The elemental platinum contained in various drug entities provided an opportunity to utilize mass based ICP-MS methods, particularly in protein enriched complex biological specimens.We have successfully established online HPLC-ICP-MS methods for analyzing cisplatin, oxaliplatin, satraplatin, their metabolites and biotransformation products in matrices such as blood plasma, cell culture medium and urine, by combining the chromatographic separation capacity with the sensitivity of the latter.These methods were further validated according to the industrial standards of USA Food and Drug Administration and applied to clinical samples of cancer patients.The major metabolites of satraplatin (JM216), the active metabolite Pt(diaminocyclohexane)dichloride of oxaliplatin, and monohydrated cisplatin were identified and measured at clinically relevant concentrations in rat, dog and human plasma following incubations, blood samples collected from cancer patients for up to 4h following a standard 2-h infusion of oxaliplatin, and in culture medium and plasma following incubation with cisplatin.We also combined size-exclusion chromatography online with ICP-MS to identify the protein species containing oxaliplatin-derived platinum.