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

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.

Suitability of cardiac blood, brain tissue, and muscle tissue as alternative matrices for toxicological evaluation in postmortem cases

“…This indicates that if the concentration in blood increases, the concentration in the alternative matrix also increases. Opioids are some of the most studied analytes in paired samples of peripheral blood and alternative matrices in the literature, where their concentration ratios in brain tissue, 21,27,32,35,[39][40][41] cardiac blood, [8][9][10]12,16,[40][41][42][43] and muscle tissue relative to peripheral blood 10,23,[40][41][42][44][45][46] are either reported or can be calculated from the concentrations. Even though some of the studies include many cases, there is a lack of consensus in the concentration ratios reported, with wide ranges generally being observed and the mean and median differing between studies.…”

“…Thus, peripheral blood is the primary choice of specimen for postmortem analysis. To evaluate the degree of PMR, concentrations in central blood are compared with concentrations in peripheral blood from authentic cases 4,8–11 . Systematic studies have compared concentrations measured upon morgue admission and at autopsy, where a high concentration ratio between the two sampling time points suggests a high degree of PMR 12–16 .…”

“…To evaluate the degree of PMR, concentrations in central blood are compared with concentrations in peripheral blood from authentic cases. 4,[8][9][10][11] Systematic studies have compared concentrations measured upon morgue admission and at autopsy, where a high concentration ratio between the two sampling time points suggests a high degree of PMR. [12][13][14][15][16] Animal studies investigating the influence of time on PMR have revealed that central blood drug concentrations change during the first hours after death.…”

Analytical Approaches for the Determination of Buprenorphine, Methadone and Their Metabolites in Biological Matrices

“…In addition, these matrices remain stable for a long time even after death [85]. A few studies have been reported in describing the determination of BUP, MTD and their metabolites in VH and skeletal tissue [39,74,85]. They concluded that VH and skeletal tissue are particularly important alternative matrices for post-mortem biochemical investigations.…”

“…Different biological specimens including urine [7,, plasma [13,20,21,35,38,40,[42][43][44][45][46][47][48][49][50][51][52][53][54][55], serum [30,[56][57][58][59], blood [15,18,22,49,[60][61][62][63], nails [64], oral fluid [17,31,55,[65][66][67][68][69], hair [47,[70][71][72], tissue [73,74] and exhaled breath condensate [75,76] have been used for the measurement of BUP, MTD and their metabo...…”