Triethyloxonium Tetrafluoroborate Derivatization and HPLC Analysis of Diethyldithiocarbamate in Plasma

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Abstract
An analytical method was developed to quantitate diethyldithiocarbamate (DDTC) in plasma [from humans] by derivatization and HPLC [high-performance liquid chromatography] analysis. A plasma sample was rapidly derivatized by addition of 10 .mu.l of Meerwein''s reagent (Et3O+BF4-) in methylene chloride. The resulting S-ethyl diethyldithiocarbamate was extracted into chloroform containing S-isopropyl diethyldithiocarbamate as the internal standard. Concentrations of DDTC were then determined by reverse phase HPLC analysis with detection at 254 nm. The detection limit for DDTC as the S-ethyl ester was 5 ng/ml. The chromatographic response was linear over the range of 250-500,000 ng/ml (R2 > 0.9995). This method was used to determine DDTC plasma levels in animal models prior to clinical use of DDTC as a kidney rescue agent for patients receiving cis-diammine-dichloroplatinum(II) (Cisplatin) chemotherapy.