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Evaluation of a test method for the measurement of urinary cyclophosphamide, 4-ketocyclophosphamide and ifosfamide.

B'Hymer-C; Cheever-KL
Toxicologist 2009 Mar; 108(1):336-337
High-Performance Liquid Chromatography-Mass Spectrometric (HPLC-MS) conditions were developed and validated for use to detect and quantitate urinary levels of cyclophosphamide (CP), 4-ketocyclophosphamide (4-ketoCP) and ifosfamide (IF). CP and IF are common antineoplastic drugs used for the treatment of many types of cancer. These compounds have known toxicity and are carcinogenic; thus, workers in the health care field, including nurses and pharmacists who prepare or dose patients, have potential exposure risk. 4-KetoCP is the primary urinary metabolite of CP and is a good potential biomarker of exposure to the parent drug. Spiked urine specimens were extracted with ethyl acetate, and then the liquid volume was reduced by evaporation. A triple quadrupole mass spectrometer (MS/MS) was used as detector with gradient reversed-phase HPLC conditions to measure the target analytes. Recovery studies using 1, 2, 4 and 15 ng/ml CP and IF spiked urine samples, and 25, 50, 100 and 375 ng/ml 4-keto-CP spiked urine samples, demonstrated good accuracy and precision. Recovery of the three compounds averaged between 97 to 105% of theory with precision [measured as percent relative standard deviation (%RSD)] as high as 8.4% for 4-ketoCP. Linearity of response was verified for concentrations of 0.5 to 25 ng/ml CP and IF in urine, and from 10 to 625 ng/ml 4-ketoCP in urine. Correlation coefficients of 0.99 or greater were obtained for all standard curves. This method offers a valid test for the determination of the urinary levels of CP, 4-ketoCP and IF as demonstrated by the accuracy and precision of the recovery studies. Disclaimers: Mention of company names and/or products does not constitute endorsement by the National Institute for Occupational Safety and Health (NIOSH). The findings and conclusions in this abstract have not been formally disseminated by NIOSH and should not be construed to represent any agency determination or policy.
Biological-effects; Biological-factors; Cancer; Carcinogens; Carcinogenicity; Chemical-hypersensitivity; Drug-therapy; Exposure-assessment; Exposure-levels; Exposure-methods; Health-care-personnel; Health-hazards; Microscopic-analysis; Microscopy; Quantitative-analysis; Statistical-analysis; Toxic-effects; Toxic-effects; Toxicopathology; Urinalysis; Urine-chemistry
Publication Date
Document Type
Fiscal Year
Issue of Publication
NIOSH Division
Priority Area
Services; Healthcare and Social Assistance
Source Name
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division