Simultaneous determination of gemcitabine, taxol, cyclophosphamide and ifosfamide in wipe samples by high‐performance liquid chromatography/tandem mass spectrometry: protocol of validation and uncertainty of measurement

Abstract

Measurable levels of anticancer agents are still detected on work surfaces in health-care settings. However, application of recent guidelines for the protection of workers' safety and health has resulted in lowered contamination levels. To assess occupational exposure to antineoplastic agents, very sensitive and specific procedures for environmental sampling and analysis are therefore needed. In the present study an assay for simultaneous determination of gemcitabine, taxol, cyclophosphamide, and ifosfamide in wipe samples, using two internal standards (trofosfamide and cephalomannine), was developed and validated by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Solid-phase extraction (SPE) was used for sample concentration and cleanup. The assay was found to be linear up to 1000 ng/wipe, with limits of quantitation of 25.0 ng/wipe for gemcitabine and taxol, and 12.5 ng/wipe for cyclophosphamide and ifosfamide. In order to investigate the effectiveness of the surface sampling, removal efficiency tests were repeated on different types of surfaces. Recovery rates of between 62 and 81% were obtained at two contamination levels (50.0 and 250 ng/100 cm2). Precision and trueness were determined on three different days. The within-day precision was found to be always less than 12.1% for all the analytes. The overall precision, expressed as relative standard deviation (RSD), was always less than 9.4%. Recoveries varying from 75.0 (gemcitabine) to 95.0% (taxol) were obtained at three levels. In order to obtain a quantitative indication of the quality of the result, the overall uncertainty of measurement (UOM) was evaluated according to the EURACHEM/CITAC guide. The relative combined uncertainty was found to be always less than 9.5%. The relative expanded uncertainty was also calculated, at three contamination levels.

Evaluation of Environmental Contaminations and Occupational Exposures Involved in Preparation of Chemotherapeutic Drugs

“…12,13) While the JSHP 31) and Mochizuki 32) recommended use of sodium hydroxide (NaOH) solution for wiping solvent, this solution decomposed paclitaxel and docetaxel. 32) We selected 20％ methanol as wiping solvent, because we will extend this measurement system to simultaneous determination of multidrugs, 13,18,33) and conˆrmed this solvent was adequate to SPE extraction with high recovery.…”

“…The procedures to obtain samples were modiˆed by previous reports. 9,13,18,19) Brie‰y, weˆrst applied 500 ng PSL/50 ml methanol to the sampling spots as internal standards. After the spots were air-dried, we wiped 800 cm 2 area (20 cm×40 cm) with a sheet of KimwipeS-200 (120 mm×215 mm, Nippon Paper Crecia, Tokyo, Japan) wetted with 1.5 ml of 20％ methanol.…”

An analysis to study trends in occupational exposure to antineoplastic drugs among health care workers

“…Thus, the ESI interface demonstrated to be the most successful hyphenation of LC and MS allowing better sensitivity and selectivity than other techniques [30]. Furthermore, LC-MS showed to be the most suitable technique to obtain reproducible assays where uncertainty parameters associated with potential analytical errors may be controlled and measured [31][32][33][34][35][36][37][38][39][40].…”

“…Since exposure to antineoplastic agents should be avoided because any detectable level is considered to be a hazard, four different LC-ESI-MS/MS methods previously developed and validated were used [34,35,44]. Environmental samples were analyzed using an API 300 triple-quadrupole mass spectrometer [36]. The assay was developed according to the 'Guide for Expression of Uncertainty in Measurement' issued by EURACHEM in 1998 and reviewed in 2000 [41].…”

Environmental Contaminations and Occupational Exposures Involved in Preparation of Chemotherapeutic Drugs

“…However, there are only several reports in the fields of occupational exposures to healthcare workers [Larson et al,2003;Sabatini et al,2005;Sottani et al,2007Sottani et al, , 2008Nussbaumer et al,2010].…”