SIMULTANEOUS DETERMINATION OF N,N',N''-TRIETHYLENETHIOPHOSPHORAMIDE, CYCLOPHOSPHAMIDE AND SOME OF THEIR METABOLITES IN PLASMA USING CAPILLARY GAS-CHROMATOGRAPHY

A sensitive assay for the simultaneous determination of N,N',N ''-trie thylenethiophosphoramide (thioTEPA), its metabolite N,N',N ''-triethyl enephosphoramide (TEPA), cyclophosphamide (CP) and its metabolite 2-de chloroethylcyclophosphamide (2DCE-CP) in plasma has been developed and validated. The analytes were determined using gas chromatography with nitrogen/phosphorus selective detection after liquid-liquid extractio n with chloroform using 100 mu l of plasma. Diphenylamine (for TEPA, t hioTEPA and 2-DCE-CP) and imipramine (for CP) were used as internal st andards. The limits of quantitation for thioTEPA, TEPA, CP and 2-DCE-C P were 5, 5, 50 and 250 ng/ml, respectively. Linear calibration curves were observed over two decades of concentration. Accuracy, within-day and between-day precision were less than 13% for all analytes. Stabil ity of the analytes proved to be satisfactory for at least 1 month, st ored at -70 degrees C. Analysis of samples obtained from patients rece iving cyclophosphamide, thioTEPA and carboplatin in a high-dose regime n demonstrated the applicability of the assay. (C) 1998 Elsevier Scien ce B.V. All rights reserved.