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"-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.
Huitema
A D
AD
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam.
Tibben
M M
MM
Kerbusch
T
T
Zwikker
J W
JW
Rodenhuis
S
S
Beijnen
J H
JH
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
D018906:Antineoplastic Agents, Alkylating; C064445:dechloroethylcyclophosphamide; D003520:Cyclophosphamide; D013852:Thiotepa; D013721:Triethylenephosphoramide