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.

Quantitative liquid chromatographic analysis of anthracyclines in biological fluids.

Anthracyclines are amongst the most widely used drugs in oncology, being part of the treatment regimen in most patients receiving systemic chemotherapy. This review provides a comprehensive summary of the sample preparation techniques and chromatographic methods that have been developed during the last two decades for the analysis of the 4 most administered anthracyclines, doxorubicin, epirubicin, daunorubicin and idarubicin in plasma, serum, saliva or urine, within the context of clinical and pharmacokinetic studies or for assessing occupational exposure. Following deproteinization, liquid-liquid extraction, solid phase extraction or a combination of these techniques, the vast majority of methods utilizes reversed-phase C18 stationary phases for liquid chromatographic separation, followed by fluorescence detection, or, more recently, tandem mass spectrometric detection. Some pros and cons of the different techniques are addressed, in addition to potential pitfalls that may be encountered in the analysis of this class of compounds.

Trace determination of anthracyclines in urine: a new high-performance liquid chromatography/tandem mass spectrometry method for assessing exposure of hospital personnel.

Health-care workers handling antineoplastic agents may be exposed to extremely low doses of these drugs. Very sensitive and specific analytical methods are therefore needed for biological monitoring. The aim of this study was to develop and validate a method for trace level determination of doxorubicin, epirubicin, daunorubicin and idarubicin in human urine, using epi-daunorubicin as an internal standard. Solid-phase extraction (SPE) was used for sample preparation. Urine samples were loaded onto Bond Elut C18 cartridges. The analytes were eluted in methylene chloride/2-propanol (1:1, v/v) and then evaporated to dryness. The residue was reconstituted with the mobile phase prior to high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) analysis. Quantitation of each analyte was performed using the multiple reaction monitoring (MRM) method. The urine assay was linear over the range 0.1-2.0 microg/L, with a lower limit of quantification (LLOQ) of 0.10 microg/L for doxorubicin and epirubicin, and 0.03 microg/L for daunorubicin and idarubicin. The respective limits of detection (LODs) were 0.04 and 0.01 microg/L. The precision and accuracy of the assay were determined on three different days. The within-series precision was found to be always less than 13.9% for all the analytes. The overall precision expressed as relative standard deviation (RSD) was always less than 10.6%. The recovery of anthracyclines was assessed at two concentrations of the range tested (0.1 and 2.0 microg/L) and it ranged from 87.7% (daunorubicin) to 102.0% (doxorubicin) and from 79.1% (daunorubicin) to 90.7% (idarubicin) for the lower and the higher level, respectively, with a RSD always less than 9.1%. The uncertainty of the present assay was also evaluated and the combined uncertainty was always less than 20% over all the days of the validation study. This is the first method that makes use of LC/MS/MS for the biological monitoring of occupational exposure to anthracyclines.

Analysis of antibiotics by capillary electrophoresis.

Recent developments in the characterization of antibiotics are reviewed. Many capillary electrophoretic techniques have been utilized in their analyses, addressing various aspects of quantifying, profiling, and monitoring. Laser-induced fluorescence detection systems demonstrated their usefulness in clinical settings and in the monitoring of residue levels in food matrices. Different sample introduction methods have been explored, enhancing detection sensitivity, or reducing or eliminating sample manipulation prior to injection.