Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in vitreous humor

Abstract

The use of vitreous humor (VH) as an alternative matrix to blood in the field of forensic toxicology has been described for numerous drugs. Interpretation of drug concentrations measured in VH, as in other matrices, requires statistical analysis of a data set obtained on a significant series. In the present study, two diagnostic tests interpreting postmortem VH concentrations of meprobamate in 117 sets of autopsy data are reported. (1) A VH meprobamate concentration threshold of 28 mg/l was statistically equivalent to that of blood meprobamate concentration threshold of 50 mg/l distinguishing overdose from therapeutic use in blood. The intrinsic qualities of the test were good, with sensitivity of 0.95 and absolute specificity of 1. (2) A novel interpretation tool is proposed, allowing blood concentration range to be evaluated, with a known probability, from VH concentration.

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review

“…As described above, the main approach used for the extrapolation of blood levels at death from VH levels is based on correlations. However, Bévalot et al [ 88 ] proposed the use of statistical data processing for interpreting meprobamate concentrations in VH, determining a VH concentration threshold to distinguish therapeutic from overdose levels. In a 117-case series (40 deemed therapeutic, 77 overdose), a threshold of 28 mg/L was determined for VH meprobamate, with sensitivity of 0.95 and absolute specificity of 1.…”

“…Rather than reflecting differential concentration between the two eyeballs, this may be a question of reproducibility related to the sampling procedure [ 81 ], of analytical problems due to the gelatinous consistency of VH [ 86 ], and of hematic contamination [ 87 ]. Bévalot et al [ 88 ], in a series of 92 human autopsies, found the left/right VH differential to be non-significant for meprobamate. Findings were similar for 3,4-methylenedioxymethamphetamine (MDMA) [ 89 ], phenytoin [ 90 ], barbiturates [ 90 ] and cocaine [ 91 ].…”

Acidic Drug Concentrations in Postmortem Vitreous Humor and Peripheral Blood

“…However, interpretation is difficult without established reference ranges or correlative data to blood concentrations. Bevalot and Downloaded from https://academic.oup.com/jat/advance-article-abstract/doi/10.1093/jat/bkz076/5613880 by University of California, San Diego Library user on 20 February 2020 colleagues (2011) showed that meprobamate, a carbamate derivative, exhibits a linear relationship between peripheral blood and vitreous humor concentrations using a logarithmic model with an R 2 of 0.94 (12). Here, we found that carbamazepine, a much more commonly prescribed drug, also exhibits a linear relationship between vitreous humor and peripheral blood and can serve as a means to estimate blood concentrations when necessary.…”

“…Vitreous humor is a clear gelatinous substance that is routinely collected from the eye during autopsy. It has been proposed as an alternative matrix when peripheral blood or urine is not available (12,13). It is thought to be less susceptible to redistribution due to its isolated nature (14); however, this has been debated (2).…”

L’humeur vitrée en toxicologie médico-légale : revue de la littérature et applications

“…Récemment, une série de cas concernant le méprobamate a été publiée par Bévalot et al Ces auteurs ont pu déterminer un facteur de corrélation entre les concentrations dans le sang et dans l'HV. Ils proposent d'appliquer comme seuil dans l'HV une concentration de 28 µg/mL qui correspondrait au seuil toxique de 50 µg/mL dans le sang [42]. Des données sont également disponibles pour quelques molé-cules de la classe des antipsychotiques comme la loxapine [43], l'olanzapine [44], la quétiapine [45].…”