Intra- and interindividual variations in urinary concentrations of endogenous gamma-hydroxybutyrate

This study was designed to determine the urinary concentrations of endogenous GHB over a one-week period, the variations that occur within those concentrations, and whether those variations are affected by normalization to urinary creatinine. Its purpose was to ascertain whether endogenous concentrations fluctuate to such an extent that they may be misinterpreted as due to GHB ingestion. Every urine void produced by eight GHB-free subjects (five males and three females) over a one-week period was individually collected and analyzed for the presence of endogenous GHB and creatinine. The results of the non-normalized and normalized concentrations were statistically analyzed. Non-normalized GHB concentrations ranged from 0.00 to 6.63 μg/mL over seven days. The coefficients of variation (CV) for the individual non-normalized data were 44.0% to 77.7%. When the data were normalized to creatinine, the concentrations ranged from 0.00 to 6.79 μg/mg. The CVs for the creatinine-normalized results were between 29.7% and 76.8%. Analysis of the differences in CVs by the paired t-test (α = 0.05) found these improvements to be statistically insignificant. Such normalization allows for correction of urinary dilution or concentration by the kidneys which may affect endogenous GHB concentrations. The data also suggest significant (p < 0.001) differences in median endogenous urinary concentrations of GHB between males and females using the Mann-Whitney test. Because of the small number of subjects in this study, further investigations are required to substantiate this observation. Some of the subjects in this study demonstrated a strong tendency to produce higher or lower GHB concentrations at consistent periods during the day. This was most evident when looking at the creatinine-normalized concentrations. The results of our study indicate that there are significant intra- and interindividual variations in the urinary concentrations of endogenous GHB. Furthermore, there are also wide variations between individuals in the total daily amount of GHB excreted in the urine. Nonetheless, no specimen's GHB concentration approached 10 μg/mL (non-normalized) or 10 μg/mg (normalized). This study of the variability in endogenous urinary GHB excretion supports the recommendation of 10 μg/mL as an appropriate cutoff to identify exogenous GHB exposure in the absence of rare genetic deficiencies such as GHB aciduria. Patients with such a deficiency should be readily identifiable through prominent symptoms, repeated urinalysis, or genetic testing.