title: Simultaneous determination of N,N',N"-triethylenethiophosphoramide, cyclophosphamide and some of their metabolites in plasma using capillary gas chromatography.
abstract: A sensitive assay for the simultaneous determination of N,N',N"-triethylenethiophosphoramide (thioTEPA), its metabolite N,N',N"-triethylenephosphoramide (TEPA), cyclophosphamide (CP) and its metabolite 2-dechloroethylcyclophosphamide (2-DCE-CP) in plasma has been developed and validated. The analytes were determined using gas chromatography with nitrogen/phosphorus selective detection after liquid-liquid extraction with chloroform using 100 microl of plasma. Diphenylamine (for TEPA, thioTEPA and 2-DCE-CP) and imipramine (for CP) were used as internal standards. The limits of quantitation for thioTEPA, TEPA, CP and 2-DCE-CP 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. Stability of the analytes proved to be satisfactory for at least 1 month, stored at -70 degrees C. Analysis of samples obtained from patients receiving cyclophosphamide, thioTEPA and carboplatin in a high-dose regimen demonstrated the applicability of the assay.
authors.affiliation: Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam.
authors.forename: A D
authors.initials: AD
authors.lastname: Huitema
authors.forename: M M
authors.initials: MM
authors.lastname: Tibben
authors.forename: T
authors.initials: T
authors.lastname: Kerbusch
authors.forename: J W
authors.initials: JW
authors.lastname: Zwikker
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000097:blood*; D002849:Chromatography, Gas / Q000379:methods*; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000097:blood*; D004355:Drug Stability; D006801:Humans; D011786:Quality Control; D012680:Sensitivity and Specificity; D013852:Thiotepa / Q000097:blood*; D013721:Triethylenephosphoramide / Q000097:blood
chemical_list: D018906:Antineoplastic Agents, Alkylating; C064445:dechloroethylcyclophosphamide; D003520:Cyclophosphamide; D013852:Thiotepa; D013721:Triethylenephosphoramide