Local administration routes have been investigated to reduce the systemic toxicity and to increase the local efficacy of cytotoxic drugs. Some examples of local administration strategies are cutaneous, intraperitoneal, intrathecal and intravesical chemotherapy. When administered locally, high local drug concentrations can be achieved with increased local efficacy and, conditionally that only small amounts of drug are absorbed into the bloodstream, low systemic toxicity. Our main purpose is to

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... ke an inventory and to comment on the availability of ultrasensitive bioanalytical assays that could determine traces of the drugs that may have passed into the bloodstream, e.g. after local application, and which may lead to the systemic toxicity. We conclude that in the last years, multiple ultrasensitive assays have been designed capable to quantitatively determine very low levels of cytotoxic agents e.g. systemically reached after local administration. Most methods are based on the hyphenated liquid chromatography with tandem mass spectrometric detection. local administration Systemic circulation ? Stability implications Stability/metabolism Implications Ultra sensitive bioanalytical assays Fig. (1) . Model for systemic exposure of locally administered agents.