DETERMINATION OF N,N',N''-TRIETHYLENTHIOPHOSPHORAMIDE IN BIOLOGICAL SAMPLES USING CAPILLARY GAS-CHROMATOGRAPHY

A sensitive assay for the determination of N,N',N ''-triethylenthiopho sphoramide (thioTEPA) in microvolumes of human plasma and urine has be en developed. ThioTEPA was analysed using gas chromatography with sele ctive nitrogen-phosphorus detection, after extraction with ethyl aceta te from the biological matrix. Diphenylamine is the internal standard. The limit of quantitation was 0.1 ng/ml, using only 100 mu l of sampl e; recoveries ranged between 85 and 100% and both accuracy and precisi on were less than 10%. Using a flame ionisation nitrogen-phosphorus de tector, the assay was not linear over the concentration range of 2-100 0 ng/ml for plasma and 10-1000 ng/ml for urine. Linearity was accompli shed in the range of 1-1000 ng/ml for plasma and urine when a thermion ic nitrogen/phosphorous detector was used. The stability of thioTEPA i n plasma proved to be satisfactory over a period of 3 months, when kep t at -20 degrees C, whereas it was stable in urine for at least 1 mont h at -80 degrees C. ThioTEPA plasma concentrations of two patients tre ated with thioTEPA are presented demonstrating the applicability of th e assay. (C) 1997 Elsevier Science B.V.