A highly sensitive UHPLC-MS/MS method for urine biological monitoring of occupational exposure to anthracycline antineoplastic drugs and routine application.

Anthracycline antineoplastic drugs (doxorubicin, epirubicin, daunorubicin) are "hazardous drugs for handling" by healthcare professionals. To monitor their occupational exposure, a highly sensitive ESI-UHPLC-MS/MS method for the assay of anthracyclines in urine was developed. The urine extraction consisted of SPE extraction method. A good linearity (r > 0.996), precision (CV < 14.4%), and accuracy (bias < 13.6%) were achieved for the three drugs. The lower limit of quantification (LOQ) was 10 ng/L. This LOQ value is equal to the LOQ of published methods except for epirubicin, for which the LOQ value is better by a factor of 10 (best published LOQ value: 100 ng/L). Applying this method in routine, more than 77 healthcare professionals occupationally exposed to anthracyclines were monitored and 77 urines were analyzed. Two healthcare professionals (2.6%) were found to be contaminated to doxorubicin and/or epirubicin. The measured concentrations ranged from 17.7 to 218 ng/L. Such an efficient analytical tool, combining both high specificity and sensitivity is essential for reliable highlight of contamination during biological monitoring of healthcare professionals widely exposed to these drugs. This anthracycline antineoplastic drugs exposure monitoring allows healthcare professionals for assessing effectiveness individual and collective protective measures and for ensuring traceability of occupational exposure to these drugs.

Biomonitoring of occupational exposure to 5-FU by assaying α-fluoro-ß-alanine in urine with a highly sensitive UHPLC-MS/MS method.

5-Fluorouracil (5-FU) is one of the most widely used antineoplastic drugs handled by healthcare professionals (HCP). To monitor occupational exposure to 5-FU, a highly sensitive ESI-UHPLC-MS/MS method was developed for the assay of its main human metabolite, α-fluoro-ß-alanine (FBAL), in urine. After a derivatization step, solid phase extraction was used for the urine. Good linearity (r > 0.996), precision (CV < 14.76%), and accuracy (bias < 12.16%) were achieved. The lower limit of quantification (LOQ), 20 pg ml-1, is the lowest one published to date. Seven urine samples from 73 HCP exposed to 5FU were positive for FBAL, indicating 5FU contamination (9.6%). FBAL urine concentrations ranged from 25 to 301 pg ml-1. Such an efficient analytical tool combining high specificity with high sensitivity is essential for the reliable detection and routine biological monitoring of healthcare professionals occupationally exposed to this widely used antineoplastic drug. This method allows biomonitoring of occupational exposure to 5-fluorouracil in a routine manner, with the aim of assessing the effectiveness of collective and individual protective measures.