scholarly journals Acidic Drug Concentrations in Postmortem Vitreous Humor and Peripheral Blood

2019 ◽  
Author(s):  
Jacqueline A Hubbard ◽  
Aylmer L Navarrete ◽  
Robert L Fitzgerald ◽  
Iain M McIntyre
Keyword(s):  
Peripheral Blood ◽  
High Performance ◽  
Vitreous Humor ◽  
Vitreous Fluid ◽  
Over The Counter ◽  
Acidic Drugs ◽  
Drug Concentrations ◽  
Postmortem Toxicology ◽  
Potential Alternative ◽  
Array Detection

Abstract Vitreous humor is a potential alternative matrix for postmortem toxicology drug screens when peripheral blood is unavailable. It is easily and reliably collected and may not suffer from the same postmortem redistribution as seen in blood. Here, we compared the concentrations of 7 acidic drugs (acetaminophen, ibuprofen, naproxen, salicylic acid, carbamazepine, phenobarbital and phenytoin) in peripheral blood and vitreous fluid collected in 89 autopsy cases. Analysis was done by high-performance liquid chromatography with diode-array detection. Overall, we found that vitreous drug concentrations were significantly lower than peripheral blood with median vitreous to peripheral blood (V/PB) ratios ranging from 0.0 to 0.6 (mean, 0.1–0.6). The correlations between the concentrations of over-the-counter analgesics in peripheral blood versus vitreous fluid were poor, with acetaminophen exhibiting the best linearity (R2 = 0.72). The antiepileptic drugs (carbamazepine, phenytoin and phenobarbital) exhibited good correlations between peripheral blood and vitreous humor, with all exhibiting an R2 ≥ 0.95. Overall, we have demonstrated the potential of vitreous fluid as an alternative matrix for the detection of select acidic drugs.

scholarly journals Methadone, Buprenorphine, Oxycodone, Fentanyl, and Tramadol in Multiple Postmortem Matrices

2021 ◽  
Author(s):  
Stine Marie Havig ◽  
Vigdis Vindenes ◽  
Åse Marit Leere Øiestad ◽  
Sidsel Rogde ◽  
Cecilie Hasselø Thaulow
Keyword(s):  
Peripheral Blood ◽  
Vitreous Humor ◽  
Pericardial Fluid ◽  
Limited Information ◽  
Blood Concentrations ◽  
Bodily Fluids ◽  
Drug Concentrations ◽  
Quantitative Analyses ◽  
Alternative Matrices ◽  
Almost All

Abstract Peripheral blood concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid, muscle, and vitreous humor have been suggested as alternatives to blood, but only a few studies have investigated the detection of opioids in these matrices. In this study, we aimed to investigate the detection of methadone, buprenorphine, oxycodone, fentanyl, and tramadol in postmortem samples of pericardial fluid, skeletal muscle, and vitreous humor, in addition to peripheral and cardiac blood; and if drug concentrations in these alternative matrices were comparable to those in peripheral blood, and thereby useful for interpretation. In most of the 54 included cases, only one opioid was detected. Methadone, oxycodone, fentanyl, and tramadol were detected in all of the alternative matrices in almost all cases, while buprenorphine was detected less often. For methadone, the concentrations in the alternative matrices, except for in vitreous humor, were relatively similar to those in peripheral blood. Larger variations in concentrations were found for buprenorphine, oxycodone, and tramadol. Quantitative analyses appeared useful for fentanyl, in all of the alternative matrices, but only four cases were included. Toxicological analyses of opioids in these alternative postmortem matrices can be useful for detection, but interpretation of quantitative results must be performed with caution.

scholarly journals Tolerability, kinetics, and efficacy of subconjunctival pefloxacin in pigmented rabbits.

1995 ◽  
Vol 39 (4) ◽  
pp. 834-838 ◽  
Author(s):  
S Marrakchi-Benjaafar ◽  
I Cochereau ◽  
F D'Hermies ◽  
J J Pocidalo
Keyword(s):  
Half Life ◽  
Maximum Concentration ◽  
High Performance ◽  
Histopathological Examination ◽  
Vitreous Humor ◽  
Subconjunctival Injection ◽  
Corneal Ulcers ◽  
Drug Concentrations ◽  
Pigmented Rabbits ◽  
The Right

Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend its clinical use, we have assessed the tolerability, kinetics, and efficacy of subconjunctival pefloxacin in phakic pigmented rabbits. The tolerability of a single subconjunctival injection of pefloxacin (0.8, 1.6, 8, or 16 mg in 0.2 ml) in the right eyes of eight rabbits was evaluated by clinical and histopathological examination. The 0.8-mg dose of pefloxacin was well tolerated. The kinetics was evaluated after a single subconjunctival injection of 0.8 mg in 18 rabbits. Animals were sacrificed at 1, 3, 5, 7, 12, or 18 h postinjection. Drug concentrations were measured by high-performance liquid chromatography. Pefloxacin was found in the cornea (maximum concentration, 18.13 micrograms/ml; half-life, 3.92 h) and in the aqueous humor (maximum concentration, 3.40 micrograms/ml; half-life, 2.14 h). Pefloxacin did not penetrate into the vitreous humor by this route. The efficacy was evaluated in an experimental model of staphylococcal corneal ulcers in eight rabbits which received two subconjunctival injections of 0.8 mg of pefloxacin at 16 and 24 h after intrastromal inoculation. The results (expressed as mean log10 CFU per milliliter +/- standard deviation) showed that pefloxacin significantly (P < 0.001) reduced the bacterial counts (4.39 +/- 0.97) compared with those in control eyes (6.46 +/- 0.69). For phakic eyes, subconjunctival pefloxacin might be of value for the treatment of corneal ulcers. Further studies are required to determine its penetration into the vitreous humor of aphakic eyes.

Endogenous Gamma-Hydroxybutyrate in Postmortem Samples

2019 ◽  
Vol 44 (3) ◽  
pp. 263-267
Author(s):  
Helen H Ha ◽  
Dani C Mata ◽  
Jay R Vargas
Keyword(s):  
Peripheral Blood ◽  
Liver Homogenate ◽  
Internal Standard ◽  
Brain Homogenate ◽  
Vitreous Humor ◽  
The Body ◽  
Matrix Analysis ◽  
Postmortem Toxicology ◽  
Gamma Hydroxybutyrate ◽  
Heart Blood

Abstract Gamma-hydroxybutyrate (GHB) is a naturally occurring molecule present in the human body as a catabolite of the neurotransmitter gamma-aminobutyrate (GABA). In the USA, GHB has a history of being manufactured illicitly and abused, with misguided proposed benefits for the body-building community and a persistent party drug with reported GHB overdoses occurring worldwide. The interpretation of GHB in postmortem biological fluids is complicated by the endogenous nature of the molecule. Analysis often requires more than one biological matrix to detect exogenous exposure, typically in urine. The analysis is further complicated by the endogenous de novo production of GHB in postmortem specimens. This work sought to examine the prevalence of endogenous GHB concentrations in postmortem toxicology samples from Orange County, CA, and to establish suitable in-house secondary matrices to confirm or rule out exogenous GHB exposure. A total of 348 postmortem heart blood samples were randomly selected and analyzed for GHB using liquid–liquid extraction followed by gas chromatography–mass spectrometry with selective ion monitoring and GHB-d6 as an internal standard. Of the 348 cases analyzed, 39 cases resulted in positive GHB detection with the median concentration of 22.45 mg/L (10.4–62.16 mg/L). None of the positive samples had suspected GHB ingestion or usage from the case report. GHB concentrations were then examined in secondary matrices collected at autopsy from the positive cases that included (when available) peripheral blood, urine, vitreous humor, liver homogenate and brain homogenate. Within the secondary matrices, GHB levels in peripheral blood compared to that of heart blood, while liver homogenate levels were variable. Quantifiable GHB levels were not identified in vitreous humor and brain homogenate samples. Our findings reaffirm the importance of multi-matrix analysis in postmortem toxicology and further confirm the utility of vitreous humor and brain tissue to distinguish exogenous GHB exposure from endogenous production.

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