Evaluation of Freezing Point Depression Osmolality for Classifying Random Urine Specimens Defined as Substituted Under HHS/DOT Criteria

This study evaluates the analytical performance characteristics of freezing point depression osmolality in urine and osmolality as a suitable analytical indicator for determining the concentration of urine specimens submitted for workplace drug testing. Specifically, this study attempted to determine the utility of urine osmolality to serve as an indicator of substitution as defined by HHS/SAMHSA criteria. Urine osmolality was validated by determining the accuracy, precision, analytical sensitivity, reportable range, and reference interval for the method. Osmolality was measured in workplace urine specimens (n = 66) with creatinine concentrations < or = 5.0 mg/dL. Comparing the results with the lower limit of the random urine reference intervals for specific gravity (1.002) and osmolality (50 mOsm/kg), 62% had specific gravities < or = 1.001, 52% had osmolalities < 50 mOsm/kg, and 47% had both a creatinine < or = 5.0 mg/dL, specific gravity < or = 1.001 and an osmolality < 50 mOsm/kg. Urine specimens (n = 311) were collected from 35 volunteers enrolled in a controlled water loading study in which at least 80 oz (2370 mL) of fluid was ingested over a 6-h period. The lowest achieved osmolality was 28 mOsm/kg. Polyuria disorders have produced abnormally low urine osmolalities (lowest reported 18 mOsm/kg) but osmolalities < or = 23 mOsm/kg have resulted in death from water intoxication. An osmolality substitution cut-off to delineate a specimen as inconsistent with normal human urine can be set at some value < 50 mOsm/kg, when used in a population of individuals with urine creatinine concentrations < or = 5.0 mg/dL.