Enzymatic assays for detecting lactose and sucrose in urine to reveal intravenous drug abuse with emphasis on buprenorphine.

Buprenorphine and methadone are commonly used medications for opioid maintenance treatment (OMT), using sublingual and oral administration, respectively. Although beneficial for OMT, these drugs can also be abused by intravenous administration. In intravenous abuse cases, the adjuvants lactose and sucrose are excreted in urine without hydrolysis to monosaccharides, since there are no disaccharidases in the blood. We validated enzymatic methods for the analysis of lactose and sucrose in urine. The analytical performance of both assays was considered appropriate for detecting intravenous drug abuse. The principle was proven by analyzing 93 postmortem (PM) urine samples for lactose, following comprehensive toxicological drug screening. In addition, 32 clinical urine samples from potential drug abusers were analyzed to assess the effect of PM changes on the assay. The mean level of lactose was low in clinical samples and relatively low in PM samples in which no drugs were found. Markedly elevated levels were seen in many of the buprenorphine positive samples, suggesting intravenous administration. Enzymatic methods could provide a simple and cost effective way to assess the intravenous administration of OMT drugs or drugs of abuse. Very high levels of glucose in urine may interfere with the assays. Furthermore, other causes for elevated urine disaccharides, such as hypolactasia and increased intestinal permeability, need to be considered in the interpretation of the results. Copyright © 2016 John Wiley & Sons, Ltd.

Post-mortem analysis of lactate concentration in diabetics and metformin poisonings.

Lactate is produced in carbohydrate metabolism under anaerobic conditions. Lactic acidosis occurs when the production of lactate exceeds its removal. In post-mortem (PM) context, the lactic acidosis is difficult to interpret due to unknown pathophysiological factors prior to death and PM changes that may affect the lactate levels. We evaluated 1865 medico-legal autopsy cases where the quantitation of glucose, lactate, and ketone bodies was performed as a part of the cause of death (CoD) investigation. Lactate was shown to ascend in a logarithmic manner as the PM interval increased until a plateau was achieved approximately after 8-10 days PM, and the elevation was caused mainly by PM changes. The lactate level was higher than the mean in cases where the CoD was diabetes mellitus type 2 (DM2) or metformin poisoning. Although there was a correlation between metformin and lactate levels, our findings suggest the DM2 and its complications were the cause for elevated lactate levels rather than metformin, since the lactate levels were similar in DM2-associated deaths where no metformin was detected. Elevated lactate levels in PM samples rather referred to metabolic disturbances often caused by DM2. An assay to detect D-lactate in PM samples was described.