Normalization of Urinary Drug Concentrations with Specific Gravity and Creatinine

Abstract

Excessive fluid intake can substantially dilute urinary drug concentrations and result in false-negative reports for drug users. Methods for correction ("normalization") of drug/metabolite concentrations in urine have been utilized by anti-doping laboratories, pain monitoring programs, and in environmental monitoring programs to compensate for excessive hydration, but such procedures have not been used routinely in workplace, legal, and treatment settings. We evaluated two drug normalization procedures based on specific gravity and creatinine. These corrections were applied to urine specimens collected from three distinct groups (pain patients, heroin users, and marijuana/ cocaine users). Each group was unique in characteristics, study design, and dosing conditions. The results of the two normalization procedures were highly correlated (r=0.94; range, 0.78-0.99). Increases in percent positives by specific gravity and creatinine normalization were small (0.3% and -1.0%, respectively) for heroin users (normally hydrated subjects), modest (4.2-9.8%) for pain patients (unknown hydration state), and substantial (2- to 38-fold increases) for marijuana/cocaine users (excessively hydrated subjects). Despite some limitations, these normalization procedures provide alternative means of dealing with highly dilute, dilute, and concentrated urine specimens. Drug/metabolite concentration normalization by these procedures is recommended for urine testing programs, especially as a means of coping with dilute specimens.

Diagnostic Accuracy and Interpretation of Urine Drug Testing for Pain Patients: An Evidence-Based Approach

“…A creatinine-corrected value will correct for a patient's hydration on the day of the test and show a decrease in the amount of nordiazepam in the urine, thus supporting the patient's claim that he or she has stopped taking the drug. It is important that reference laboratories not only provide creatininecorrected results but that they give doctors or staff help in interpreting the data (Cone et al, 2009). It is also important for the physician to know if a patient has attempted to obscure UDT results by diluting a urine specimen.…”

False Negative Results in Testing for Drugs of Abuse from Diluted Urine

“… Some laboratories, in particular in area of doping controls, concentrated (spiked) urine samples or special normalization procedures that are based on specific gravity and creatinine content within the measured urine are recommended for accurate urine drug testing programs [24,25].…”

Quantification of a Methadone Metabolite (EDDP) in Urine: Assessment of Compliance

“…Additionally, reports prove that ratios in a light or infrequent user will decrease faster than those in a heavy or frequent user. Cone et al 33 reported on normalization of cocaine urine testing results to urine creatinine. Quantitative benzoylecgonine (BE) to urine creatinine levels allowed for the differentiation of positive BE levels arising from washout and from positive BE levels resulting from new cocaine use.…”