Development and validation of methods for environmental monitoring of cyclophosphamide in workplaces

Abstract

Methods to monitor contamination of workplaces with antineoplastic drugs have been developed and validated. Cyclophosphamide (CP) was used as a model compound as it is one of the most commonly used antineoplastic drugs. A wipe sampling method to detect contamination with CP at surfaces was developed. A personal air sampling method to sample gas and vapour on solid sorbent tubes and particles with filters was also developed. Wipe and filter samples were extracted and sorbent samples were eluted, all with ethyl acetate. The samples were analysed with liquid chromatography tandem mass spectrometry.2 H 6 -labelled cyclophosphamide was used as an internal standard. The between-day precision was 2-5% for wipe samples, 4-6% for sorbent samples and 3-8% for filter samples. The limit of detection was 0.02 ng CP per sample for the wipe and filter methods and 0.03 ng CP per sample for the solid sorbent method. Wipe sampling on surfaces made of different materials resulted in mean recoveries between 78-106%. The desorption recovery was between 97-102% for the wipe samples, 97% for the sorbent samples and 101% for the filter samples. Samples were stable for up to 2 months at 5 1C and À20 1C and for about 2 d at room temperature. The developed methods were applied to the measurement of contamination with CP in a hospital pharmacy. Trace amounts of CP, 1.3 and 1.4 ng, were detected on surfaces in the pharmacy.

Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals

“…This can be explained by the lower sensitivity of the CP method, leading to the incapacity to measure values below 30 μg, than in the cases of 5FU (LOQ=1,000 ng) and PTX (LOQ=50 ng). Additionally, CP is unstable at room temperature (Hedmer et al 2004). In an opposite way, PTX presented higher number of contaminated surfaces (21.7 %) when comparing with the other two drugs studied (4.6 % for CP and 10.7 % for 5FU) ( Table 4).…”

Hygienic guidance values for wipe sampling of antineoplastic drugs in Swedish hospitals

“…Cyclophosphamide (CP) and ifosfamide (IF) are two commonly used antineoplastic drugs in Swedish hospitals and for which sensitive analytical methods are available. [12][13][14] The International Agency for Research on Cancer (IARC) has classified CP as carcinogenic to humans and IF as 5 probably carcinogenic to humans. [15][16][17] Thus, CP and IF were used as indicator substances for surface contamination of antineoplastic drugs.…”

Development of a Method for Screening Spill and Leakage of Antibiotics on Surfaces Based on Wipe Sampling and HPLC-MS/MS Analysis

“…The previously developed HPLC-MS/MS method for determination of CP [11] was investigated for the analysis of various antibiotic substances. A similar method has also been presented for determination of antibiotics in sewage waters [7].…”

“…Similar methods have also been developed for screening spill and leakage of antineoplastic drugs. These latter screening methods are frequently based on wipe sampling followed by gas chromatography-mass spectrometry (GC-MS) [9], liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) [10][11][12], or voltammetry [13][14] (see Ref 1 for more references).…”

“…The aim of this study has been to develop and validate a screening method for antibiotic substances taking its basics from a previously developed method for determination of cyclophosphamide (CP) and ifosfamide (iF), based on wipe sampling followed by an HPLC-3 (20) MS/MS analysis [11,[15][16] of the samples. The method will be validated for screening a large number of substances used as active components in frequently used antibiotics in wipe samples collected from various frequently occurring surface materials.…”