include the required level of uncertainty, expressed either as a standard uncertainty or as expanded uncertainty.10 In practice, the uncertainty regarding the result may arise from many sources. It is there- fore very important to look closely at all possible sources of uncertainty (including sampling, matrix effects and interferences, environmental conditions and approximations in the measurement method and procedure). Each source of uncertainty is then treated separately to obtain the contribution from that source (uncertainty component). The total uncertainty, termed “combined standard uncertainty”, is a standard deviation obtained by combining all the uncertainty components. In analytical chemistry, an expanded uncertainty is often used, which provides an interval within which the value of the measurand is believed to lie with a higher level of confidence.
The main results of our work are presented in a series of papers.11–18
the most important antineoplastic agents the instrumental technique used, precision (CV%), trueness, limit of detection (LOD), limit of quantitation (LOQ) and combined relative uncertainty at a given concentration level are listed. It is noteworthy that use of high- performance instrumentation such as HPLC-MS/MS allows simultaneous analysis of different drugs with low LODs.16,18
The evaluation of uncertainty
further increases the confidence that can be placed on the results. Note that a method is conventionally considered reliable when the total uncertainty is less than 30%. Our results comply with this rule, making the methods at issue suitable for application to exposure assessment.
After gaining consistent analytical results, the next step is interpreting them. In this respect, itcould be useful to have a sort of reference table for each drug and for each kind of matrix, which could ensure a uniform interpretation of the analytical results across the countries.
In addition, the practice should be to keep on record any analysis (along with an updated list of exposed personnel), the frequency and duration of exposure, and reports of incidents, injuries or any equipment failure. This database is essential for future reference in order to assess any possible relationship between occupational exposure and adverse health effects.
It is still true that the percentage of positive samples has significantly decreased in recent years, but in fact there is no safe exposure level above zero.8,19 Nevertheless, despite the large amount of effort and all the progress made, contamination still occurs. What is actually required here is a comprehensive approach: analytical aspects cannot be separated from monitoring strategy and from education and training. That is why personnel must take their share of responsibility. Education and training is undoubtedly a key component of the overall system.
Conclusions Last but not least, existing guidelines call for economically feasible tests. However, a mandatory monitoring system involves costs and this, along with the necessary technical requirements, may be a limiting factor in implementation. ●
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11. Sottani C, Tranfo G, Faranda P, et al. Highly sensitive high-performance liquid chromatography/selective reaction monitoring mass spectrometry method for the determination of cyclophosphamide and ifosfamide in urine of health care workers exposed to antineoplastic agents. Rapid Commun Mass Spectrom 2005;19(19):2794-800.
12. Minoia C, Turci R, Sottani C, et al. Application of high performance liquid chromatography/tandem mass spectrometry in the environmental and biological monitoring of health care personnel occupationally exposed to cyclophosphamide and ifosfamide. Rapid Commun Mass Spectrom 1998;12:1485-93.
13. Turci R, Micoli G, Minoia C. Determination of methotrexate in environmental samples by solid phase extraction and high performance liquid chromatography: ultraviolet or tandem mass spectrometry detection? Rapid Commun Mass Spectrom 2000;14:685-91.
14. Micoli G, Turci R, Arpellini M, Minoia C. Determination of 5-fluorouracil in environmental samples by solid-phase extraction and high performance liquid chromatography with ultraviolet detection. J Chromatogr B 2001;750:25- 32.
15. Sottani C, Zucchetti M, Zaffaroni M, et al. Validated procedure for simultaneous trace level determination of the anti-cancer agent gemcitabine and its metabolite in human urine by high-performance liquid chromatography with tandem mass spectrometry. Rapid Commun Mass Spectrom 2004;18(10):1017-23.
16. Sottani C, Tranfo G, Bettinelli M, et al. Trace determination of anthracyclines in urine: a new high-performance liquid chromatography/tandem mass spectrometry method for assessing exposure of hospital personnel. Rapid Commun Mass Spectrom 2004;18(20):2426-36.
17. Spezia S, Bocca B, Forte G, et al. Comparison of inductively coupled plasma mass spectrometry techniques in the determination of platinum in urine: quadrupole vs sector field. Rapid Commun Mass Spectrom 2005;19:1551-6.
18. Sottani C, Turci R, Schierl R, et al. 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. Rapid Commun Mass Spectrom 2007;5;21(7):1289-96.
19. Turci R et al. Biological monitoring of hospital personnel occupationally exposed to antineoplastic agents. Toxicol Lett 2002;134(1- 3):57-64.
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