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 computed from the volume (liters) of the sample and the time (hours) elapsed since the last voiding. The adjustment is to a mean output of 0.05 L/h.

3. Creatinine concentration. This is the most frequently used adjustment. Creatinine is excreted by glomerular filtration at a relatively constant rate of 1.0-1.6 g/day. Urinary creatinine concentration can be determined by spectrometric or kinetic methods based on the Jaffé alkaline picrate reaction, enzymatic methods, and methods based on mass spectrometry and liquid chromatography [28]. The adjusted value is the quantity of the biomarker per unit quantity of creatinine.

There are other considerations to be taken into account when adjusting urinalysis data for dilution:

1. Adjustment to the creatinine level is not appropriate for compounds, such as methanol, that are excreted in the kidney primarily by tubular secretion.

2. Since the mechanism of excretion of a biomarker can be altered if the urine is very concentrated or very dilute, measurements on samples, having creatinine concentrations outside the range 0.5 to 3 g/L or having specific gravities outside the range 1.010 to 1.030, are unreliable [5].

3. Adjustment for creatinine concentration, while correcting for dilution, introduces additional variation, which must be considered when the data are evaluated. Among the factors affecting the rate of creatinine excretion are the muscularity of the subject, physical activity, urine flow, time of day, diet, pregnancy, and disease [27].

Quality Assurance. Good data require the utilization of an effective quality assurance program. In 1992, regulations implementing the Clinical Laboratory Improvement Amendments (CLIA) of 1988 were published by the Health Care Finance Administration and the Public Health Service to ensure that analysis of human specimens was done accurately and under good quality control procedures [29]. Any analysis of human specimens that can be used by a health care practitioner to assess the health of the individual or used in the diagnosis, prevention, or treatment of disease or impairment falls under the CLIA guidelines. Since, as a minimum, biological monitoring data are used to prevent occupational disease or impairment, CLIA guidelines apply. Key components of the CLIA quality assurance program include:

1. Strict management of specimen collection, handling, storage, and transportation, thus ensuring sample integrity

2. Thorough verification of a method by the laboratory before use on field specimens

3. High level of analytical quality control

4. Participation in proficiency testing programs, if available

5. Documented instrument evaluation and maintenance programs

6. Investigation of communication failures and complaints

7. Documentation of performance and corrective actions

Ethical Considerations. There are several ethical issues that must be considered before initiating a biological monitoring procedure [30, 31]:

1. Method should be appropriate for the requirements of the investigation. 1/15/98 Manual of Analytical Methods