UPLC-MS/MS method for simultaneous determination of cyclophosphamide, docetaxel, doxorubicin and 5-fluorouracil in
Carla Brigagão Pacheco da Silva1, Isabelle Prado Julio1, Giuliano Engler Donadel1
1Laboratory of Toxicants and Drug Analysis - LATF, Faculty of Pharmaceutical Sciences, Federal University of Alfenas - Unifal-MG, Rua Gabriel Monteiro da Silva, 700, Alfenas, Minas Gerais 37130.000, Brazil.
Introduction:
There is certainly a great benefit to treatment with antineoplastic drugs for cancer patients with a life-threatening disease. However, for the workers who are exposed to these agents as part of their work practice, precautions should be taken to eliminate or reduce exposure as much as possible.
Objective:
The aim of this study is to develop and validate a wipe sampling procedure followed by liquid chromatographic separation with electrospray ionization and a tandem mass spectrometric detection method for the simultaneous determination of cyclophosphamide (CP), docetaxel (DOC), doxorubicin (DOXO) and 5-fluorouracil (5-FU).
Method:
The chromatographic separation was carried out in 15min by applying a gradient elution of 0.1% formic acid and acetonitrile. MS/MS was performed on a triple quadrupole instrument in the multiple reaction monitoring (MRM) mode.
Results:
The analytical range was linear between 3.5 to 300ng/mL for CP, 4 to 300ng/mL for DOC and DOXO and 2 to 300ng/mL for 5-FU. The present method offers a high sensitivity, with detection limits of 1.0ng/mL for CP, DOXO and DOC and 0.5ng/mL for 5-FU. The selectivity, accuracy (relative standard error between 82.3 and 113.9%) and precision (relative standard deviation between 1.2 and 14.2%) make the method suitable for the routine determination of these drugs to estimate the occupational exposure of personnel handling.
Conclusions:
The developed method allows a reliable assessment of exposure, which is one of the steps for evaluation the risk inherent to workers in contact with antineoplastic drugs.
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