Liquid chromatographic-mass spectrometric determination of the novel, recently identified thioTEPA metabolite, thioTEPA-mercapturate, in urine.
An assay for the quantitative determination of the mercapturic acid conjugate of N,N',N"-triethylenethiophosphoramide (thioTEPA-mercapturate) in human urine has been developed. ThioTEPA-mercapturate, a recently identified metabolite of the alkylating anticancer agent thioTEPA, was analyzed using LC-MS and with direct sample injection. Sulphadiazine was used as internal standard. Linearity was accomplished in the therapeutic relevant range of 1-25 microg/ml; recovery was 84% and both accuracy and precision were less than 20% for the lower limit of quantification (1.0 microg/ml) and less than 10% for the other concentration levels. The stability of thioTEPA-mercapturate proved to be satisfactory over a period of 2 months, when kept at -80 degrees C. ThioTEPA-mercapturate urine concentrations of two patients treated with thioTEPA are presented demonstrating the applicability of the assay for clinical samples.
van Maanen
M J
MJ
Department of Pharmaceutical Analysis, Utrecht University, The Netherlands. m.j.vanmaanen@pharm.uu.nl
Beijnen
J H
JH
D000111:Acetylcysteine / Q000378:metabolism*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D013852:Thiotepa / Q000378:metabolism*
D013852:Thiotepa; D000111:Acetylcysteine