Analysis of GHB and 4-Methyl-GHB in Postmortem Matrices after Long-Term Storage

Abstract

Postmortem heart blood, peripheral blood, vitreous humor, urine, and bile specimens from 26 autopsy cases were analyzed for the presence of gamma-hydroxybutyric acid (GHB) and gamma-methyl gamma-hydroxybutyric acid (4-Me-GHB) after long-term freezer storage. Cases were selected for which exogenous GHB, gamma-butyrolactone (GBL), gamma valerolactone (GVL), or 1,4-butanediol use was not suspected. One documented positive GHB case subjected to the same storage conditions was also evaluated for comparison. Specimens did not contain any preservatives or additives except heart blood, which contained sodium fluoride (2% w/v). The results of the analysis for GHB in vitreous humor (n = 26) demonstrated, with one exception, concentrations below the limit of detection for the method (5 mg/L). In the exception case, the value was determined to be 7 mg/L. Documented cases of GHB positive fatalities showed vitreous humor concentrations (n = 6) that exceeded this range by a factor of 12 or more. There was no apparent relationship between storage times and GHB concentrations. The data developed in this study demonstrate a postmortem endogenous range for GHB in vitreous humor that is less than or equal to 7 mg/L. Studies of the stored GHB-positive case demonstrated no significant change in concentration over the time period studied. None of the specimens analyzed in this study contained detectable amounts of 4-Me-GHB. This would support the contention that when 4-Me-GHB is detected, it is most likely due to the exogenous consumption of GVL.

Gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL) and 1,4-butanediol (1,4-BD; BDO): A literature review with a focus on UK fatalities related to non-medical use

“…These levels overlap with the range of reported fatal GHB intoxications with concentrations of 27 to 2937 mg/L and could possibly lead to misinterpretation as intoxication (Andresen et al, 2011). Concentrations in non-fatal intoxications as high as 551 mg/L have been reported (Couper and Marinetti, 2002;Elliott, 2004b;Van Sassenbroeck et al, 2007), whilst fatalities with concentrations of 303 mg/L have been recorded (Duer et al, 2001;Marinetti et al, 2005).…”

“…Other substances and levels Dosages Marinetti, 2001 Therapeutic Bl 24-88 mg/L Palatini et al, 1993 Drowsiness -25 mg/kg (oral) -80 mg/L peak plasma Baselt, 2008 Amnesia -10 mg/kg; sleep/deep sedation -20-30 mg/kg; recreational -35 mg/kg; anaesthesia ->50mg/L Helrich et al, 1964 Sleep -50 mg/kg (IV) peak blood 170 mg/L Hoes et al, 1980 Sleep -75mg/kg (oral) peak plasma at 2 h 90 mg/L, plasma at 6 h 9 mg/L; 100 mg/kg (oral) ur peak at 4 h 1100 mg/L Baselt, 2008 Sleep/deep sedation -20-30 mg/kg Baselt, 2008 Recreational -35 mg/kg Baselt, 2008 Anaesthesia ->50mg/L Endogenous PM GHB Busardò et al, 2014 Deaths with no GHB ingestion Range ND-11.6; mean 4.6; median 4.7 Elliott, 2001 Deaths with no GHB ingestion Range 0-197 Fieler et al, 1998 Deaths with no GHB ingestion 3.2-168 Marinetti et al, 2005 Deaths with no GHB ingestion 11-97 Moriya & Hashimoto, 2004 Deaths with no GHB ingestion 0-43.0 Stephens et al, 1999 Deaths with no GHB ingestion 5-77 Anaethesia study Helrich et al, 1964 Surgical patients (N = 14) 100mg/kg of GHB, intravenous, no pre-meds or other drugs administered …”

Gamma-hydroxybutyric acid stability and formation in blood and urine

“…Due to the growing number of cases of overdose or sexual assault where GHB application is suspected, there are increasing demands for routine toxicological examinations in laboratories. However, the interpretation of data related to biological specimens and pos-tmortem blood in particular, has become very problematic and controversial, as has been shown previously by many authors [7][8][9][10][11][12][13][14][15][16][17].…”

Metabolism of Levulinate in Perfused Rat Livers and Live Rats

“…The five-carbon 4-hydroxypentanoate, as a racemic mixture, is a new drug of abuse used in lieu of 4-hydroxybutyrate, which is now a controlled substance in the United States (7)(8)(9)(10)(11). Based on our previous work, we hypothesized that calcium levulinate could be used as a precursor of 4-hydroxypentanoate, i.e.…”