Some strategies for improving specificity and sensitivity in the analysis of anti-cancer drugs

Abstract

Some approaches are discussed for introducing specificity and sensitivity into analytical methods for anti-tumour agents which include a liquid chromatographic step. Various modes of HPLC have been exploited to monitor these drugs specifically and at therapeutically low levels. The use of column switching technology and chemical derivatization techniques to enhance both specificity and sensitivity are discussed. Multiple columns (linked through switching valves) containing packings exhibiting different affinities for the analytes cisplatin and riboxamide provide (a) a high degree of selectivity with convenient analysis times, (b) the opportunity for preconcentration of analytes, (c) improved longevity of analytical columns, (d) a solution to the 'general elution problem', and (e) allow direct application of biological fluid to the HPLC system. The use of chemical derivatization techniques (pre- and post-column) to achieve improved sensitivity and altered chromatographic and chemical properties of these and other anti-tumour agents (galactitol, tamoxifen, emetine) is also described. The high chemical reactivity of many anti-tumour agents often requires their rapid derivatization after a biological sample is drawn to prevent chemical degradation in the sample vial. The use of chemical and photochemical derivatization techniques combined with spectrophotometric, fluorometric and voltammetric detectors illustrates the power and utility of derivatization technology in trace drug analysis.