Enzymatic Assay for GHB Determination in Forensic Matrices

Grenier, Vincent; Huppé, Geneviève; Lamarche, Martine; Mireault, Pascal

doi:10.1093/jat/bks053

Cited by 13 publications

(5 citation statements)

References 15 publications

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“…A number of simpler and more economical enzymatic methods are available for the analysis of GHB in biological fluids [ 97 , 98 ]. One of these involves oxidation with the enzyme GHB dehydrogenase and the co-factor NAD + which becomes reduced to NADH, and the later is determined quantitatively by UV spectrometry at 340 nM [ 99 ].…”

Section: Methodsmentioning

confidence: 99%

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GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

Busardò¹,

Jones²

2015

175

227

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The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant withdrawal symptoms. There is no evidence-based protocol available to deal with GHB withdrawal, apart from administering benzodiazepines.

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Section: Methodsmentioning

confidence: 99%

“…A recent photometric procedure was adapted to work with a Thermo Scientific MGC-240 auto-analyzer and this furnished a rapid method for determination of GHB in blood, vitreous humor and urine [ 97 ]. The authors reported a good correlation when paired samples were analyzed with a more specific GC-MS method.…”

Section: Methodsmentioning

confidence: 99%

GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

Busardò¹,

Jones²

2015

175

227

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“…The diagnosis of SSADH-D is presently based on the detection of GHB in the organic acid profile in urine [13]. In addition, GHB can be measured in other body fluids [23,24]. Genetic testing should always be used to confirm biochemical findings that point to SSADH-D. SSADH-D can present as an autism spectrum disorder [25], and the ALDH5A1 gene has been included in the commercially available autism gene panels [26].…”

Section: Metabolitementioning

confidence: 99%

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Didiášová

Banning

Brennenstuhl

et al. 2020

Cells

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Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degrees of mental retardation, autism, ataxia, and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved curative therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials, and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs, and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between researchers and patients.

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“…The diagnosis of SSADH-D is presently based on detection of GHB in the organic acid profile in urine [11]. In addition, GHB can be measured in other body fluids [17,18], but this is usually done only for research purposes and is not routinely used. In addition, genetic testing can be the first diagnostic step and should always follow a biochemical suspicion for confirmation of the diagnosis.…”

mentioning

confidence: 99%

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Didiášová¹,

Banning²,

Brennenstuhl³

et al. 2020

Preprint

View full text Add to dashboard Cite

Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by the impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degree of mental retardation, autism, ataxia and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential use of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between the researchers and the patients.

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Enzymatic Assay for GHB Determination in Forensic Matrices

Cited by 13 publications

References 15 publications

GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

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