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

Abstract

Investigating toxicological causes of death may require alternative matrices when the usual ones are lacking. Whereas forensic toxicology uses bile almost only for xenobiotic screening, a diagnostic test interpreting postmortem bile concentrations of meprobamate is reported. Based on 128 sets of autopsy data, its intrinsic qualities were good, with 0.95 sensitivity and 0.93 specificity. In a French forensic population, the positive and negative predictive factors were 0.90 and 0.97, respectively. It is a useful means of revealing overdoses where blood samples are not available or of confirming blood tests when postmortem redistribution is suspected.

State-of-the-art of bone marrow analysis in forensic toxicology: a review

“…However, the application of these data, mostly obtained on animal models with standardized protocols, to human autopsy cases, subject to uncontrollable and often unknown postmortem conditions, requires further study. When correlation with blood is not established, a statistical approach could be interesting to determine either a toxicity threshold or the likelihood that a drug level, quantified in an alternative matrix, corresponds to overdose rather than therapeutic use [59,80]. Another aspect to consider for quantitative interpretation is the postmortem changes of BM concentration.…”

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

“…The approach was similar to that described by Fanton et al [14]. We sought to determine the VH meprobamate concentration corresponding to the 50 mg/l blood concentration threshold above which overdose is generally agreed to be suspected [20,21].…”

“…Analytical methods Blood samples were analyzed using a technique previously described [14], adapted and validated for meprobamate assay in VH as follows; 20 μl methanol solution at 1 mg/ml in carisoprodol (internal standard (IS)) were added to 200 μl VH. The mixtures were diluted in 1 ml ammoniac buffer (pH=9.5, 0.07 M) and extracted with 1.5 ml of a chloroform-isopropanol (9:1, v:v) mixture.…”

“…Although VH meprobamate concentrations were described in some case reports [17,18], no investigation of the correlation between blood and VH concentrations has been performed on a statistically significant series. Previously, the interpretation of meprobamate concentrations in bile was reported [14]; the present study looked at VH meprobamate concentrations, with the same objective and a similar approach.…”

“…There was great variability in results according to the molecule considered and to experimental conditions. Despite that meprobamate has been replaced by other sedative agents in some countries, it stays a drug frequently detected on postmortem toxicological investigation [14,15]. It is a carbamate derivative, prescribed as an anxiolytic but with well-established abuse potential [16].…”