Suspected North Carolina counterfeit pill-involved deaths, 2020-2022.

The NC Office of the Chief Medical Examiner regularly assumes jurisdiction over deaths that are suspicious, unusual or unattended by a medical professional. In recent years, the presence of counterfeit pills is occasionally suggested by investigatory notes and/or scene findings that document reported consumption of prescription drugs, or prescription drugs on scene, which are not reflected in the final autopsy findings after toxicological analysis of the decedent's blood samples. Counterfeit pill consumption is a major public health hazard worthy of attention from the forensic toxicology community. Seventy-five cases from January 2020 to December 2022 serve as a convenience sample of cases where prescription pills including formulations of alprazolam, oxycodone and hydrocodone were specifically referenced during the death scene investigation as recently consumed, yet an unexpected substance was found during toxicological analysis rather than the expected pharmaceutical drug. Of note, novel benzodiazepines detected included flualprazolam, etizolam, clonazolam metabolite (8-aminoclonazolam), bromazolam, flubromazolam and desalkylflurazepam. Decedents' ages ranged from 16 to 69, across 33 different NC counties. Case notes indicated that eight of the decedents obtained pills through direct personal relationships, six decedents obtained them from "the street" and one decedent likely purchased pills online. Pills were largely consumed orally or through insufflation. Seven case reports contained indication that decedents knew or suspected the counterfeit nature of their pills. This study describes the context and characteristics of 2020-2022 suspected counterfeit pill-involved deaths in NC to further the understanding of the forensic science community, law enforcement partners, public health stakeholders and those potentially at risk through the consumption of counterfeit pills.

Buprenorphine-Related Deaths in North Carolina from 2010 to 2018.

Buprenorphine (BUP) is a commonly prescribed medication for the treatment of opioid use disorder (OUD). As prescriptions increase in North Carolina, BUP is more frequently encountered statewide in routine postmortem casework. Between 2010 and 2018, there were 131 select cases investigated by the Office of the Chief Medical Examiner where BUP was detected in peripheral blood and considered a primary cause of death (COD), with no other opioids present and no other non-opioid substances found in the lethal range. The decedents ranged in age from 14 to 64 years, with 67% male. The mean/median peripheral blood concentrations were 4.1/2.1 ng/mL for BUP and 7.8/3.4 ng/mL for its metabolite, norbuprenorphine. These postmortem blood concentrations overlap antemortem therapeutic concentrations in plasma reported in the literature for opioid-dependent subjects receiving sublingual maintenance therapy. The pathologist considered scene findings, prescription history, autopsy findings, toxicological analysis and decedent behavior prior to death to conclude a drug-related COD. Many of the deaths were complicated by the presence of other central nervous system depressants along with contributory underlying cardiovascular and respiratory disease. The three most prevalent additive substances were alprazolam, ethanol and gabapentin, found in 67, 36 and 32 cases out of 131, respectively. Interpreting BUP involvement in a death is complex, and instances may be underestimated in epidemiological data because of the lack of a defined toxic or lethal range in postmortem blood along with its good safety profile. As expansion of access to OUD treatment becomes a priority, awareness of the challenges of postmortem interpretation is needed as increased use and diversion of BUP are inevitable.

The Trouble With Kratom: Analytical and Interpretative Issues Involving Mitragynine.

Mitragynine is the primary active alkaloid in the leaves of the tropical tree Mitragyna speciosa, and goes by the popular names "Kratom", biak-biak and maeng da. Mitragynine is increasingly seen in forensic toxicology casework including driving under the influence of drugs and medicolegal death investigation cases. The toxicity of mitragynine continues to be debated in the scientific community as advocates highlight its long history of use in Southeast Asia and testimonials to its benefits by present-day users, while opponents point to an increasing number of adverse events tied to mitragynine use in Western societies. Quantitative reports of mitragynine in biological specimens from forensic investigations in the literature are sparse and may be influenced by poor analyte stability and inadequate resolution of mitragynine from its diastereomers, which could lead to falsely elevated concentrations and subsequently render those reported concentrations inappropriate for comparison to a reference range. Over the course of 27 months, 1,001 blood specimens submitted to our laboratory tested positive for mitragynine using a sensitive and specific quantitative LC-MS/MS method; concentrations ranged from 5.6-29,000 ng/mL, with mean and median concentrations of 410 ± 1,124 and 130 ng/mL, respectively. Mitragynine presents an analytical challenge that requires a method that appropriately separates and identifies mitragynine itself from its isomers and other related natural products. We describe a validated analytical method and present a short series of case reports that provide examples of apparent adverse events, and the associated range of mitragynine concentrations. This type of analytical specificity is required to appropriately interpret mitragynine concentrations detected in biological specimens from forensic casework and assess its potential toxicity.

Unimolecular reactions of CH(2)BrCH(2)Br, CH(2)BrCH(2)Cl, and CH(2)BrCD(2)Cl: identification of the Cl-Br interchange reaction.

The recombination reactions of CH(2)Br and CH(2)Cl radicals have been used to generate vibrationally excited CH(2)BrCH(2)Br and CH(2)BrCH(2)Cl molecules with 91 kcal mol(-1) of energy in a room-temperature bath gas. The experimental unimolecular rate constants for elimination of HBr and HCl were compared to calculated statistical rate constants to assign threshold energies of 58 kcal mol(-1) for HBr elimination from C(2)H(4)Br(2) and 58 and 60 kcal mol(-1), respectively, for HBr and HCl elimination from C(2)H(4)BrCl. The Br-Cl interchange reaction was demonstrated and characterized by studying the CH(2)BrCD(2)Cl system generated by the recombination of CH(2)Br and CD(2)Cl radicals. The interchange reaction was identified from the elimination of HBr and DCl from CH(2)ClCD(2)Br. The interchange reaction rate is much faster than the rates of either DBr or HCl elimination from CH(2)BrCD(2)Cl, and a threshold energy of congruent with43 kcal mol(-1) was assigned to the interchange reaction. The statistical rate constants were calculated from models of the transition states that were obtained from density functional theory using the B3PW91 method with the 6-31G(d',p') basis set. The model for HBr elimination was tested versus published thermal and chemical activation data for C(2)H(5)Br. A comparison of Br-Cl interchange with the Cl-F and Br-F interchange reactions in 1,2-haloalkanes is presented.