Determining the prevalence and concentrations of baclofen, gabapentin and pregabalin in post-mortem femoral-vein blood samples from Coroners’ cases

Abstract

Objectives: Gabapentin (GBP) and pregabalin (PGL) misuse is increasing and is associated with an increasing number of deaths. Baclofen (BLF) is also being misused and deaths have been observed. However, it is impossible to gauge the extent of this issue with current selective post-mortem (PM) toxicological screening processes. This thesis describes the development of a method for screening and quantifying BLF, GBP and PGL in PM femoral-vein blood using protein precipitation followed by analysis using liquid chromatography-tandem mass spectrometry. PM femoral-vein bloods, from Coroners’ cases, were screened to determine the prevalence of BLF, GBP and PGL; all positive samples were quantified. The risks associated with poly-substance use, and the extent of under-reporting of these drugs in deaths due to selective toxicological screening were investigated. Setting and study population: Coroners’ cases submitted for routine toxicology testing from jurisdictions in London and South East England between 1st January 2016 and 31st December 2017. 3750 deceased aged ≥ 16 years were analysed. Results: Of 3750 samples analysed, 21 (0.6%) were positive for BLF, 118 (3.1%) for GBP and 229 (6.1%) were positive for PGL. If selective rather than routine screening of BLF, GBP and PGL had been performed, BLF would have been under-reported by 43%, GBP by 57.6% and PGL by 53.7% in deaths. The prevalence of GBP and PGL was 2.3 times and 4.1 times greater in heroin users compared to non-heroin users, respectively. It was determined that a GBP concentration of ≥ 40 µg/mL and a PGL of ≥ 20 µg/mL should be considered as significant. Conclusions: This study suggests GBP and PGL should be included in the routine screening of Coroners’ toxicology. GBP and PGL are being widely used along with heroin and other opioids, increasing the possible risk of toxicity due to respiratory depression. BLF-related deaths were rarely seen.