Validated method for occupational cyclophosphamide monitoring using LC-MS/MS and a Poroshell 120 column

Abstract

Pharmacy staff and health care workers in hospitals may be exposed to antineoplastic drugs during cancer chemotherapy. Sensitive methods should be used to monitor the occupational exposure in biofluids such as urine. In this study, a sensitive method for cyclophosphamide determination in urine with high recovery was developed and validated for monitoring occupational exposure. Triple liquid-liquid extraction with ethyl acetate/dichloromethane (phi(r) - 3 : 1; 6.0 mL) was applied. Good separation of cyclophosphamide and ifosfamide was achieved in a 9.0 min analysis, using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). Limit of detection and limit of quantification were 0.07 ng mL(-1) and 0.11 ng mL(-1), respectively. Repeatability (RSD, %) was <= 12.74 %. Inter-day and inter-analyst precision values (RSD, %) were <= 13.94 % and 12.59 %. Mean recovery for three different concentrations was (101.62 +/- 6.05) %. The validation results were fitted for the purpose of routine monitoring of occupational cyclophosphamide exposure in hospital staff. (C) 2015 Institute of Chemistry, Slovak Academy of Sciences