Clinical Evaluation of Gamma Hydroxybutyric Acid (GHB) and its Glucuronide in Biological Matrices of Succinic Semi Aldehyde Dehydrogenase Deficient Patients

Abstract

Gamma hydroxybutyric acid (GHB), an endogenous metabolite, is an agonist towards both GHB and GABAB receptors. GHB is elevated during illicit drug use and in patients with heritable succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder of GABA degradation. Previous reports have postulated that the glucuronide conjugate (GHB‐gluc) may represent a urinary biomarker for GHB intoxication. The objective of the present work was to examine the level of GHB‐gluc in SSADH‐deficient patients and its applicability as a potential clinical biomarker. Urine was quantified for GHB and GHB‐gluc on an AB Sciex 6500 mass spectrometer. Semi validation of the urine method was conducted using plasma and cerebrospinal fluid (CSF). SSADH patient urine, plasma and CSF and healthy volunteer control urine and plasma were collected and quantified for GHB and GHB‐gluc using LC‐MS/MS. Absolute quantification of GHB and GHB‐gluc in patient urine samples revealed an inverse correlation between GHB and GHB‐gluc (r2, 0.6; p value<0.05). Relative to control samples, the GHB‐gluc was only moderately elevated in patient samples (~15%). The GHB‐gluc was below the limit of quantification (25 ng/ml) in patient CSF and was not discernible between groups in plasma specimens. This work indicates that GHB‐conjugation may occur primarily in the kidney, or that a fraction of the GHB‐gluc is excreted in the bile.Acknowledgement: The generous support of the SSADH Association (www.ssadh.net) is gratefully acknowledged.