Comparison of exposure assessment methods in occupational exposure to benzene in gasoline filling-station attendants.

The aim of this study was to assess gasoline filling-station attendants' exposure to benzene and to determine which biological exposure index (BEI), trans,trans-muconic acid (t,t-MA) or S-phenylmercapturic acid (S-PMA), shows better correlation with environmental exposure. Exposure to benzene was measured using passive samplers (Radiello) attached to the collar of the overalls of subjects (n=33) just before the work-shift (approximately 8h); analysis was performed by GC-FID. S-PMA and t,t-MA were determined, respectively, by an immunochemiluminescent assay based on specific monoclonal antibodies and by HPLC-UV at 264 nm. Both methods of biological monitoring were performed on beginning and end-shift urine samples, and expected t,t-MA and S-PMA values were calculated. Smoking habits and life-style were ascertained by means of a questionnaire. Both environmental and biological monitoring data showed that benzene exposure for gasoline filling-station attendants was low when compared with the respective ACGIH limit values (means-benzene: 0.044 mg/m(3); t,t-MA: 171 microg/g creatinine; S-PMA: 2.7 microg/g creatinine). No significant correlation was found between exposure to benzene and t,t-MA or S-PMA excretion data. The use of expected values was also experimented for S-PMA and t,t-MA. This consists of calculating, on the basis of the known half-life of the benzene metabolite, the concentration of that metabolite that a worker should present at the end of the work-shift, the difference between this value and the value actually found is a measure of benzene exposure during work. The use of expected values in biological monitoring did not improve correlations. At these low benzene levels, environmental monitoring seems to be the best method of evaluating individual exposure. However, biological monitoring remains useful, as a mean of assessing group exposure.

Highly sensitive high-performance liquid chromatography/selective reaction monitoring mass spectrometry method for the determination of cyclophosphamide and ifosfamide in urine of health care workers exposed to antineoplastic agents.

In recent years, the potential for exposure of health care workers to antineoplastic agents has led to the establishment of more restrictive government and professional standards and procedures for handling cytotoxic drugs. Therefore, the detection of low exposure levels is a new and important aim of biological monitoring. In the present paper we report an assay for the simultaneous determination of cyclophosphamide (CP) and ifosfamide (IF) in urine, using electrospray ionization liquid chromatography/tandem mass spectrometry with selective reaction monitoring (HPLC/SRM-MS). A rapid sample preparation procedure uses a solid-phase extraction stage with C18 columns. The urine assay is linear over the range 0.02 to 0.4 microg/L, with lower limits of quantification (LLOQs) of 0.02 and 0.04 microg/L for CP and IF. The accuracy and precision have been carried out through the validation study. The intra-day precision, expressed as relative standard deviation (RSD), is found to be always less than 14.7% for both analytes. The overall precision, assessed on three different days, is less than 15.0%. The recovery of ozaxaphosphorines ranges from 83.5% (CP) to 88.5% (IF) with a RSD always less than 14.6%. The uncertainty of the overall method was also evaluated, to identify possible sources of error. The combined uncertainty was less than 25% over all the days of the validation study. This method is selective and sensitive enough to determine trace levels of CP and IF in a range of urine concentrations relevant to performing low exposure assessment.

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.