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DESI-MS2: a rapid and innovative method for trace analysis of six cytostatic drugs in health care setting

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Abstract

With the aim of establishing exposure levels for hospital personnel preparing and administering cytostatic drugs (CDs), here, we present an innovative screening method based on the use of the desorption electrospray ionization (DESI) interface coupled with a hybrid quadrupole linear ion trap mass spectrometer. A rapid, simple, and sensitive procedure was developed for the simultaneous surface monitoring of cyclophosphamide, dacarbazine, methotrexate, vincristine, gemcitabine, and cytarabine. Since analytes were in the solid state, a novel approach based on the use of passive samplers was combined with the direct analysis of wipes. A PTFE-printed glass slide was used as a passive sampler, while hydrophobic centers of Swiffer® cloths were judged extremely efficient as wipe samplers. After the sampling period, the CD collectors were directly processed with the DESI-MS system without any further treatment. MS/MS confirmatory analysis was conducted using selected reaction monitoring in the positive ion mode and detection limits were evaluated. Values were at the picograms per square millimeter levels on the passive collector and at the picograms per square centimeter levels for the wipe ones. Direct determination on solid-state samples combined with mass spectrometry selectivity provided a powerful tool so far unapplied to occupational hygiene.

DESI interface detail (spray emitter and MS inlet) with 3D spacefill structures of the six cytostatic drugs analyzed

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References

  1. Van Berkel GJ, Pasilis SP, Ovchinnikova O (2008) Established and emerging atmospheric pressure surface sampling/ionization techniques for mass spectrometry. J Mass Spectrom 43(9):1161–1180

    Article  Google Scholar 

  2. Alberici MR, Simas RC, Sanvido GB, Romão W, Lalli PM, Benassi M, Cunha IBS, Eberlin MN (2010) Ambient mass spectrometry: bringing MS into the “real world”. Anal Bioanal Chem 398:265–294

    Article  CAS  Google Scholar 

  3. Takáts Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306(5695):471–473

    Article  Google Scholar 

  4. Takáts Z, Wiseman JM, Cooks RG (2005) Ambient mass spectrometry using desorption electrospray ionization (DESI): instrumentation, mechanisms and applications in forensics, chemistry, and biology. J Mass Spectrom 40(10):1261–1275

    Article  Google Scholar 

  5. Cody RB, Laramee JA, Durst HD (2005) Versatile new ion source for the analysis of materials in open air under ambient conditions. Anal Chem 77(8):2297–2302

    Article  CAS  Google Scholar 

  6. Petucci C, Diffendal J, Kaufman D, Mekonnen B, Terefenko G, Musselman B (2007) Direct analysis in real time for reaction monitoring in drug discovery. Anal Chem 79(13):5064–5070

    Article  CAS  Google Scholar 

  7. Williams JP, Patel VJ, Holland R, Scrivens JH (2006) The use of recently described ionisation techniques for the rapid analysis of some common drugs and samples of biological origin. Rapid Commun Mass Spectrom 20(9):1447–1456

    Article  CAS  Google Scholar 

  8. Van Berkel GJ, Ford MJ, Deibel MA (2005) Expanded electrochemical capabilities of the electrospray ion source using porous flow-through electrodes as the upstream ground and emitter high-voltage contact. Anal Chem 77(24):8041–8049

    Article  Google Scholar 

  9. Takáts Z, Cotte-Rodriguez I, Talaty N, Chen H, Cooks RG (2005) Direct, trace level detection of explosives on ambient surfaces by desorption electrospray ionization mass spectrometry. Chem Commun 15:1950–1952

    Article  Google Scholar 

  10. Hall KA, Green M, Newton P, Fernandez F (2005) Desorption electrospray ionization orthogonal TOF MS and LC-TOF MS studies of counterfeit and low-quality antimalarial drugs. Proceedings of the 53rd ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX, June 5–9

  11. Chen H, Talaty N, Takáts Z, Cooks RG (2005) Desorption electrospray ionization mass spectrometry for high-throughput analysis of pharmaceutical samples in the ambient environment. Anal Chem 77(21):6915–6927

    Article  CAS  Google Scholar 

  12. Soparawalla S, Salazar GA, Perry RH, Nicholas M, Cooks RG (2009) Pharmaceutical cleaning validation using non-proximate large-area desorption electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 23:131–137

    Article  CAS  Google Scholar 

  13. Weston DJ, Bateman R, Wilson ID, Wood TR, Creaser C (2005) Direct analysis of pharmaceutical drug formulations using ion mobility spectrometry/quadrupole-time-of-flight mass spectrometry combined with desorption electrospray ionization. Anal Chem 77(23):7572–7580

    Article  CAS  Google Scholar 

  14. Leuthold LA, Mandscheff JF, Fathi M, Giroud C, Augsburger M, Varesio E, Hopfgartner G (2006) Desorption electrospray ionization mass spectrometry: direct toxicological screening and analysis of illicit Ecstasy tablets. Rapid Commun Mass Spectrom 20(2):103–110

    Article  CAS  Google Scholar 

  15. Eberlin LS, Haddad R, Sarabia Neto RC, Cosso RG, Maia DRJ, Maldaner AO, Zacca JJ, Sanvido GB, Romão W, Vaz BG, Ifa DR, Dill A, Cooks RG, Eberlin MN (2010) Instantaneous chemical profiles of banknotes by ambient mass spectrometry. Analyst 135(10):2453–2744

    Article  Google Scholar 

  16. Cooks RG, Ouyang Z, Takats Z, Wiseman JM (2006) Ambient mass spectrometry. Science 311(5767):1566–1570

    Article  CAS  Google Scholar 

  17. Harris GA, Nyadong L, Fernandez FM (2008) Recent developments in ambient ionization techniques for analytical mass spectrometry. Analyst 133(10):1297–1301

    Article  CAS  Google Scholar 

  18. McDevitt JJ, Lees PSJ, McDiarmid MA (1993) Exposure of hospital pharmacists and nurses to antineoplastic agents. JOM 35(1):57–60

    CAS  Google Scholar 

  19. Rombaldi F, Cassini C, Salvador M, Saffi J, Erdtmann B (2009) Occupational risk assessment of genotoxicity and oxidative stress in workers handling anti-neoplastic drugs during a working week. Mutagenesis 24(2):143–148

    Article  CAS  Google Scholar 

  20. Cavallo D, Ursini CL, Perniconi B, Di Francesco A, Giglio M, Rubino FM, Marinaccio A, Iavicoli S (2005) Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. Mutat Res 587(1–2):45–51

    CAS  Google Scholar 

  21. Dranitsaris G, Johnston M, Poirier S, Schueller T, Milliken D, Green E, Zanke B (2005) Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta-analysis of the literature. J Oncol Pharm Pract 11(2):69–78

    Article  Google Scholar 

  22. IARC (1990) IARC monographs on the evaluation of the carcinogenic risk to humans, vol 50. Pharmaceuticals drugs. World Health Organization, International Agency for Research on Cancer, Lyons, France

  23. IARC (2009) IARC monographs on the evaluation of carcinogenic risks to humans. World Health Organization, International Agency for Research on Cancer, Lyons, France

  24. Connor TH, Anderson RW, Sessink PJ, Spivey SM (2002) Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. Am J Health Syst Pharm 59(1):68–72

    CAS  Google Scholar 

  25. Burgaz S, Karahalil B, Canli Z, Terzioglu F, Ançel G, Anzion RBM, Bos RP, Hüttner E (2002) Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations. Hum Exp Toxicol 21(3):129–135

    Article  CAS  Google Scholar 

  26. Fransman W, Roeleveld N, Peelen S, de Kort W, Kromhout H, Heederik D (2007) Nurses with dermal exposure to antineoplastic drugs: reproductive outcomes. Epidemiology 18(1):112–119

    Article  Google Scholar 

  27. Falck K, Gröhn P, Sorsa M, Vainio H, Heinonen E, Holsti LR (1979) Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1(8128):1250–1251

    Article  CAS  Google Scholar 

  28. Ng LM, Jaffe N (1970) Possible hazards of handling antineoplastic drugs. Pediatrics 46(4):648–649

    CAS  Google Scholar 

  29. Donner AL (1978) Possible risk of working with antineoplastic drugs in horizontal laminar flow hood. Am J Hosp Pharm 35(8):900

    CAS  Google Scholar 

  30. Hedmer M, Tinnerberg H, Axmon A, Jönsson BAG (2008) Environmental and biological monitoring of antineoplastic drugs in four workplaces in a Swedish hospital. Int Arch Occup Environ Health 81(7):899–911

    Article  CAS  Google Scholar 

  31. Brouwers EEM, Huitema ADR, Bakker EN, Douma JW, Schimmel KJM, van Weringh G, de Wolf PJ, Schellens JHM, Beijnen JH (2007) Monitoring of platinum surface contamination in seven Dutch hospital pharmacies using inductively coupled plasma mass spectrometry. Int Arch Occup Environ Health 80(8):689–699

    Article  CAS  Google Scholar 

  32. Sottani C, Porro B, Comelli M, Imbriani M, Minoia C (2010) An analysis to study trends in occupational exposure to antineoplastic drugs among health care workers. J Chromatogr B 878(27):2593–2605

    Article  CAS  Google Scholar 

  33. Connor TH (2006) Hazardous anticancer drugs in health care: environmental exposure assessment. Ann NY Acad Sci 1076:615–623

    Article  CAS  Google Scholar 

  34. DesRoches P (2003) Cytotoxic drug handling—monitoring in the occupational health setting. AAOHN J 51:106–108

    Google Scholar 

  35. Mason HJ, Blair S, Sams C et al (2005) Exposure to antineoplastic drugs in two UK hospital pharmacy units. Ann Occup Hyg 49(7):603–610

    Article  CAS  Google Scholar 

  36. Turci R, Minoia C (2006) Residual hazard assessment related to handling of antineoplastic drugs: safety system evolution and quality assurance of analytical measurement. Ann N Y Acad Sci 1076:659–656

    Article  Google Scholar 

  37. Acampora A, Castiglia L, Miraglia N, Pieri M, Soave C, Liotti F, Sannolo N (2005) A case study: surface contamination of cyclophosphamide due to working practices and cleaning procedures in two Italian hospitals. Ann Occup Hyg 49(7):611–618

    Article  CAS  Google Scholar 

  38. Roberts S, Khammo N, McDonnell G, Sewell JG (2006) Studies on the decontamination of surfaces exposed to cytotoxic drugs in chemotherapy workstations. J Oncol Pharm Pract 12(2):95–104

    Article  CAS  Google Scholar 

  39. NIOSH: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health (NIOSH) (2004) Alert: preventing occupational exposure to antineoplastic and other hazardous drugs in healthcare settings. DHHS (NIOSH), Publication No. 2004-165

  40. González-Bayón L, González-Moreno S, Ortega-Pérez G (2006) Safety considerations for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion. EJSO 32(6):619–624

    Google Scholar 

  41. Benoit L, Cheynel N, Ortega-Deballon P, Giacomo GD, Chauffert B, Rat P (2008) Closed hyperthermic intraperitoneal chemotherapy with open abdomen: a novel technique to reduce exposure of the surgical team to chemotherapy drugs. Ann Surg Oncol 15(2):542–546

    Article  Google Scholar 

  42. Turci R, Sottani C, Spagnoli G, Minoia C (2003) Biological and environmental monitoring of hospital personnel exposed to antineoplastic agents: a review of analytical methods. J Chromatogr B 789(2):169–209

    Article  CAS  Google Scholar 

  43. Pieri M, Castiglia L, Basilicata P, Sannolo N, Acampora A, Miraglia N (2010) Biological monitoring of nurses exposed to doxorubicin and epirubicin by a validated liquid chromatography/fluorescence detection method. Ann Occup Hyg 54(4):368–376

    Article  CAS  Google Scholar 

  44. Minoia C, Turci R, Sottani C, Schiavi A, Perbellini L, Angeleri S, Draicchio F, Apostoli P (1998) 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 12(20):1485–1493

    Article  CAS  Google Scholar 

  45. Connor TH, Anderson RW, Sessink PJ, BroadWeld L, Power LA (1999) Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States. Am J Health Syst Pharm 56:1427–1432

    CAS  Google Scholar 

  46. Castiglia L, Miraglia N, Pieri M, Simonelli A, Basilicata P, Genovese G, Guadagni R, Acampora A, Sannolo N, Scafarto MV (2008) Evaluation of occupational exposure to antiblastic drugs in an Italian hospital oncological department. J Occup Health 50:48–56

    Article  CAS  Google Scholar 

  47. Sottani C, Rinaldi P, Leoni E, Poggi G, Teragni C, Delmonte A, Minoia C (2008) Simultaneous determination of cyclophosphamide, ifosfamide, doxorubicin, epirubicin and daunorubicin in human urine using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry: bioanalytical method validation. Rapid Commun Mass Spectrom 22(17):2645–2659

    Article  CAS  Google Scholar 

  48. Sugiura SI, Asano M, Kinoshita K, Tanimura M, Nabeshima T (2011) Risks to health professionals from hazardous drugs in Japan: a pilot study of environmental and biological monitoring of occupational exposure to cyclophosphamide. J Oncol Pharm Pract 17(1):14–19

    Article  CAS  Google Scholar 

  49. Sottani C, Turci R, Schierl R, Gaggeri R, Barbieri A, Violante FS, Minoia C (2007) 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 21(7):1289–1296

    Article  CAS  Google Scholar 

  50. Nussbaumer S, Geiser L, Sadeghipour F, Hochstrasser D, Bonnabry P, Veuthey J-L, Fleury-Souverain S (2011) Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces. Anal Bioanal Chem. doi:10.1007/s00216-011-5157-2

  51. IARC (2011) IARC monographs on the evaluation of the carcinogenic risk to humans, vol 100A. A review of human carcinogens: pharmaceuticals. World Health Organization, International Agency for Research on Cancer, Lyons, France

  52. IARC (1987) IARC monographs on the evaluation of the carcinogenic risk to humans, vol 26, suppl. 7. Overall evaluation of carcinogenicity: an updating of IARC monographs, volumes 1–42. World Health Organization, International Agency for Research on Cancer, Lyons, France

  53. Soparawalla S, Salazar GA, Sokol E, Perry RH, Cooks RG (2010) Trace detection of non-uniformly distributed analytes on surfaces using mass transfer and large-area desorption electrospray ionization (DESI) mass spectrometry. Analyst 135:1953–1960

    Article  CAS  Google Scholar 

  54. Altman DG, Bland JM (1994) Diagnostic tests: sensitivity and specificity. BMJ 308(6943):1552

    Article  CAS  Google Scholar 

  55. Thyssen JB, Skare L, Lundgren L, Menné T, Johansen JD, Maibach HI, Lidén C (2010) Sensitivity and specificity of the nickel spot (dimethylglyoxime) test. Contact Dermatitis 62:279–288

    Article  Google Scholar 

  56. Barbieri A, Sabatini L, Indiveri P, Bonfiglioli R, Lodi V, Violante FS (2007) Simultaneous determination of low levels of methotrexate and cyclophosphamide in human urine by micro liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 20:1889–1893

    Article  Google Scholar 

  57. Ling G, Zhang P, Sun J, Zhang W, Fu Q, Zhang T, Deng Y, He Z (2011) An LC-MS/MS method for simultaneous determination of vincristine and verapamil in rat plasma after oral administration of a dual agent formulation. Biomed Chromatogr 25:963–969

    Article  CAS  Google Scholar 

  58. Sun Y, Sun J, Wen B, Shi S, Xu Y, Chen Y, Wang Y, Pan C, Zhang C, Zhang T, He Z (2008) High-performance liquid chromatography/tandem mass spectrometry method for the simultaneous determination of cytarabine and its valyl prodrug valcytarabine in rat plasma. J Chromatogr B 870:121–125

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Occupational Hygiene Department, Chemical Agents Laboratory, Italian Workers’ Compensation Authority (INAIL)–ISPESL Area, Via Fontana Candida 1, 00040, Monte Porzio Catone, Rome, Italy

    Giovanni Fabrizi, Marzia Fioretti, Lucia Mainero Rocca & Roberta Curini

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  1. Giovanni Fabrizi
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  2. Marzia Fioretti
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  3. Lucia Mainero Rocca
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  4. Roberta Curini
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Correspondence to Giovanni Fabrizi.

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Published in the special issue Euroanalysis XVI (The European Conference on Analytical Chemistry) with guest editor Slavica Ražić.

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Fabrizi, G., Fioretti, M., Mainero Rocca, L. et al. DESI-MS2: a rapid and innovative method for trace analysis of six cytostatic drugs in health care setting. Anal Bioanal Chem 403, 973–983 (2012). https://doi.org/10.1007/s00216-011-5626-7

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