Evaluation of a Test Method for the Measurement of Urinary Cyclophosphamide, 4-Ketocyclophosphamide and Ifosfamide

Details

• Personal Author:
  B'Hymer, Clayton ; Cheever KL
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Biological Factors Carcinogens Drug Therapy Environmental Monitoring Hazardous Substances Health Personnel Hypersensitivity Microbiology Neoplasms Occupational Health Safety Toxicology Urine

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• Keywords:
  Biological-effects Biological-factors Cancer 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 Toxicopathology Urinalysis Urine-chemistry

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  336-337
• Volume:
  108
• Issue:
  1
• NIOSHTIC Number:
  nn:20035291
• Citation:
  Toxicologist 2009 Mar; 108(1):336-337
• CAS Registry Number:
  Cyclophosphamide (CAS RN 50-18-0)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Services ; Healthcare and Social Assistance
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ac842e57c5c8cd3cfa7c44f0660ddc638ef2d7d1dd2d10a0bc6d415a09029a706bf370a1385b9f1c6feb26994d1a001a80f4d0ab66c62ea4da101059f6a9d106
• Download URL:
  https://stacks.cdc.gov/view/cdc/187199/cdc_187199_DS1.pdf
• File Type:
  [PDF - 1.59 MB ]