RESUMO
A wipe sampling procedure followed by a simple ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of six cytotoxic drugs: 5-fluorouracil (5FU), doxorubicin (DOXO), epirubicin (EPI), ifosfamide (IF), cyclophosphamide (CP) and gemcitabine (GEM), as surrogate markers for occupational exposure. After a solid-phase extraction of wiping filter on 10â¯×â¯10 cm surface, the separation was performed within 6.5â¯min, using a gradient mobile phase and the analytes were detected by mass spectrometry in the multiple reaction ion monitoring mode. The method was validated according to the recommendations of the US Food and Drug Administration. The method was linear (r2â¯>â¯0.9912) between 2.5 and 200â¯ng per wiping sample (25 to 2000â¯pg/cm2) for 5FU, doxorubicin and epirubicin and between 0.2 and 40â¯ng per wiping sample (2 to 400â¯pg/cm2) for cyclophosphamide, ifosfamide and gemcitabine. The lower limits of quantification were 2.5â¯ng (25â¯pg/ cm2) for 5FU, doxorubicin and epirubicin, and 0.2â¯ng (2â¯pg/cm2) for CP, IF and GEM. Within-day and between-day imprecisions were <14.0, 10.6, 11.1, 8.7, 11.2 and 10.9% for 5-fluorouracil, doxorubicin, epirubicin, ifosfamide cyclophosphamide and gemcitabine, respectively. The inaccuracies did not exceed 2.7, 10.9, 1.1, 4.5, 1.6 and 2.9% for the studied molecules, respectively. This new sensitive validated method for surface contamination studies of cytotoxics was successfully applied on different localizations in hospital. This approach is particularly suitable to assess occupational exposure risk to cytotoxic drugs.
Assuntos
Citotoxinas/análise , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Antineoplásicos/análise , Cromatografia Líquida , Ciclofosfamida/análise , Desoxicitidina/análogos & derivados , Desoxicitidina/análise , Doxorrubicina/análise , Epirubicina/análise , Contaminação de Equipamentos/prevenção & controle , Fluoruracila/análise , Ifosfamida/análise , Estudos de Amostragem , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , GencitabinaRESUMO
An improved liquid chromatography-mass spectrometry method for the determination of pemetrexed in human plasma was developed and validated using a simple quadrupole LC-MS and a new SPE cartridge (Plexa Bond Elut). The analysis was achieved with a C18 analytical column using a mobile phase consisting of formic acid/acetonitrile and isocratic flow for 7 min. The linear ranges (r(2)>0.99) were found from 5 to 5000 ng/mL. The lower limit of detection was 2.5 ng/mL. Within-day and between-day precisions were less than 7.2% and inaccuracy did not exceed 2.8%. This new method is suitable to support pharmacokinetic studies and drug monitoring.