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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 26, Number 6, September 2002,
pp. 340-346
Intra- and Interindividual Variations in Urinary Concentrations
of Endogenous Gamma-Hydroxybutyrate*
Marc A. LeBeau
Chemistry Unit, FBI Laboratory, Federal Bureau of Investigation, Washington,
D.C. 20535
Robert H. Christenson and Barry Levine
University of Maryland, Department of Pathology, Baltimore, Maryland 21201
W. David Darwin and Marilyn A. Huestis
Chemistry and Drug Metabolism, IRP, NIDA, NIH, Baltimore, Maryland 21224
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 (a = 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. Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
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