Biological monitoring of drugs

Introduction
Biological monitoring (biomonitoring) in occupational safety and health is the detection of substances (biomarkers) in biological samples of workers, compared to reference values. This article is limited to chemical exposures. Biomonitoring can help in exposure assessment of speciï¬c chemicals, characterisation of exposure pathways and potential risks. Biomarkers can detect the exposure, the effect, or reveal susceptibility. Biomonitoring may be interpreted at group or individual level. Most common media are urine and blood. While multitudes of substances can be measured, there are still only limited numbers of validated methods and limit values with scientifically proven background. The first paper on occupational biomonitoring was published in the USA, and worldwide mainstreaming started in the 1980s.
Definition
Human biomonitoring can be defined as the method for assessing human exposure to chemicals or their effects by measuring these chemicals, their metabolites or reaction products in human specimens. Biomonitoring involves measurements of biomarkers in bodily fluids, such as blood, urine, saliva, breast milk, sweat, and other specimens, such as faeces, hair, teeth, and nails. In the area of occupational medicine or occupational hygiene, biomonitoring is to be understood as the examination of biological materials of employees for the quantitative determination of hazardous substances, their metabolites or their biochemical and/or biological parameters. Within the occupational context, biomonitoring may help assess actual worker risk, where air monitoring alone may seriously underestimate the total uptake of certain substances.
Biological monitoring of hospital pharmacy
For evaluation of the risk borne by hospital pharmacy personnel exposed to antineoplastic agents, the incorporation of cyclophosphamide, ifosfamide, and platinum-containing drugs was quantified by the determination of urinary concentrations. In addition, the induction of micronuclei (MN) and sister-chromatid-exchange (SCE) rates in peripheral blood lymphocytes were studied for correlation with the urinary excretion of cytostatic drugs. Cyclophosphamide and ifosfamide were determined in 24-h urine samples using gas chromatography with electron capture (detection limit 2.5 μg/l). Voltammetric analysis enabled the determination of platinum concentrations of 4 ng/l. Heparinized blood (20 ml) was drawn and lymphocytes were cultured for MN and SCE studies.
In all, 13 hospital pharmacists and pharmacy technicians regularly involved in the preparation of cytostatic drugs participated in this investigation (7 persons represent a follow-up group). All subjects applied standard safety precautions, including the use of a vertical laminar air-flow hood, protective gowns, and latex gloves. On the day of urine sampling an average of 4,870 mg cyclophosphamide, 5,580 mg ifosfamide, and 504 mg platinum-containing drugs were handled. The excretion of 5 and 9 μg cyclophosphamide/1 urine was measured in two samples, respectively.
An elevated level of urinary platinum was found in one pharmacist (22.3 ng/g creatinine) in comparison with a nonexposed control group. Mean frequencies of MN and SCE did not differ significantly between the drug exposed group and control group. The employees who had incorporated chemotherapeutic agents were part of the follow-up group and, thus, particularly cautious and sensitive to a possible hazard. The results emphasize the necessity of improving personal protection of hospital pharmacy personnel occupationally exposed to cytostatic drugs and support the importance of biological monitoring.
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Clinical Pharmacology and Toxicology Research
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