Quantification of cyclophosphamide and its metabolites in urine using liquid chromatography/tandem mass spectrometry

Rapid Communications in Mass Spectrometry : RCM
Dirk KaselUwe Fuhr

Abstract

A reliable and easy to use liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous quantification of urinary concentrations of cyclophosphamide (CP) and its main metabolites excreted in urine, i.e. N-dechloroethylcyclophosphamide (DCL-CP), 4-ketocyclophosphamide (4KetoCP), and carboxyphosphamide (CarboxyCP). Sample preparation consisted of dilution of urine with an aqueous solution of the internal standard D(4)-CP and methanol, and centrifugation. LC/MS/MS detection was performed using a triple-quadrupole mass spectrometer working in selected reaction monitoring mode. All analytes were quantified in a single run within 11.5 min. The limits of detection were 5 ng/mL for CP and 4KetoCP, 1 ng/mL for DCL-CP, and 30 ng/mL for CarboxyCP. Quantification ranges were adjusted to the expected concentrations in 24-h urine collections of patients treated with a polychemotherapy regimen (3-175 microg/mL for CP, 0.5-27 microg/mL for 4KetoCP and 0.17-9 microg/mL for CarboxyCP and DCL-CP, respectively). The method was validated according to international guidelines of the ICH and the FDA.

Citations

Mar 3, 2012·Environmental Science and Pollution Research International·Cristian Gómez-CanelaJosep Caixach
Apr 4, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Thomas F KalhornJeannine S McCune
Sep 28, 2014·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Francine Attié de CastroVera Lucia Lanchote
Apr 1, 2012·Acta Pharmaceutica Sinica. B·Duan Wang, Hongbing Wang
Oct 4, 2011·Talanta·Susanne NussbaumerSandrine Fleury-Souverain
Jun 1, 2017·The Analyst·Nicolas GuichardSandrine Fleury-Souverain

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