First inter-laboratory comparison exercise for the determination of anticancer drugs in aqueous samples

Abstract

The results of an inter-laboratory comparison exercise to determine cytostatic anticancer drug residues in surface water, hospital wastewater and wastewater treatment plant effluent are reported. To obtain a critical number of participants, an invitation was sent out to potential laboratories identified to have the necessary knowledge and instrumentation. Nine laboratories worldwide confirmed their participation in the exercise. The compounds selected (based on the extent of use and laboratories capabilities) included cyclophosphamide, ifosfamide, 5-fluorouracil, gemcitabine, etoposide, methotrexate and cisplatinum. Samples of spiked waste (hospital and wastewater treatment plant effluent) and surface water, and additional non-spiked hospital wastewater, were prepared by the organising laboratory (Jožef Stefan Institute) and sent out to each participant partner for analysis. All analytical methods included solid phase extraction (SPE) and the use of surrogate/internal standards for quantification. Chemical analysis was performed using either liquid or gas chromatography mass (MS) or tandem mass (MS/MS) spectrometry. Cisplatinum was determined using inductively coupled plasma mass spectrometry (ICP-MS). A required minimum contribution of five laboratories meant that only cyclophosphamide, ifosfamide, methotrexate and etoposide could be included in the statistical evaluation. z-score and Q test revealed 3 and 4 outliers using classical and robust approach, respectively. The smallest absolute differences between the spiked values and the measured values were observed in the surface water matrix. The highest within-laboratory repeatability was observed for methotrexate in all three matrices (CV ≤ 12 %). Overall, inter-laboratory reproducibility was poor for all compounds and matrices (CV 27-143 %) with the only exception being methotrexate measured in the spiked hospital wastewater (CV = 8 %). Random and total errors were identified by means of Youden plots.

A Fully Automated Online SPE-LC-MS/MS Method for the Determination of 10 Pharmaceuticals in Wastewater Samples

“…The pharmaceutical compounds targeted in this study consisted of eight anticancer drugs, one antidepressant, and one antihypertensive. According to recent studies, C18-based analytical columns are the most suitable and often employed for the analysis of a similar group of compounds in water [ 14 , 30 , 32 ]. In this work, we tested three reversed-phase C18 analytical columns of which one column had additional polar functionality.…”

“…The continuous rise of cancer cases has led to the increased use of anticancer drugs and a further increase in their use in the years to come can be foreseen [ 14 , 15 ]. Anticancer drugs (also known as antineoplastics) are generally administered in hospitals and, thus, hospital wastewater is considered as the one of the various routes through which those compounds reach the aquatic environment [ 16 ].…”

Antineoplastic drugs and their analysis: a state of the art review

“…4,9,10 Most of the reported methods are based on the use of liquid chromatography (LC) coupled with UV spectrophotometry (UV) 11,12,13,14 or mass spectrometry (MS), when there was a need for high selectivity and/or sensitivity. [15][16][17][18][19][20][21][22]23,24,25,26,27,28,29,30,31,32,33,34 Limits of detection 51 In our opinion, ELSD is not recommended for analysing pemetrexed since this molecule is UV-active and ELSD is often less sensitive and selective than the commonly used UV detectors. A methodology including a PP step followed by LC-MS analysis was also developed for the determination of raltitrexed in human plasma with a limit of quantification (LOQ) of 2 ng mL −1 .…”

“…LOD of 1.7 ng mL −1 was reached for the analysis of 5FU in effluents using an SPE-CE-UV method. 106 Gas chromatography (GC) coupled to MS was also used for the analysis of 5FU, 113,114,27 but the time consuming and tedious derivatisation step means low popularity of GC for the analysis of these non-volatile compounds. 2.1.3.…”

Degradation of (E)- and (Z)-Endoxifen: Kinetics, By-products Identification and Toxicity Assessment.

“…However, the actual concentration of endoxifen in wastewater and natural water bodies has been poorly documented (Borgatta et al, 2015). The lack of technology and the know-how to measure endoxifen in laboratories are handicaps in order to determine its concentration in wastewater and surface water (Heath et al, 2016;Kovalova, Siegrist, Singer, Wittmer, & McArdell, 2012). Ferrando-Climent, Rodriguez-Mozaz, & Barceló (2013) detected but did not quantify endoxifen in two hospital wastewater samples, while a study by Negreira et al (2014) reported a concentration of 96 ng L -1 of endoxifen in a wastewater effluent sample.…”