No abstract

The in vitro production of gamma-hydroxybutyrate (GHB) in antemortem urine samples was demonstrated over an eight-month period. Positive chemical ionization-gas chromatography-mass spectrometry (PCI-GC-MS) was used to detect trace amounts of GHB produced in vitro under certain storage conditions. Freshly prepared drug-free human urine was stored at 21, 4, and -20 degrees C in the presence of preservative. Although artifactual production of GHB occurred more rapidly at elevated temperatures, the presence of an antimicrobial agent (sodium azide) in the drug-free urine control did not impede GHB production. The preliminary data suggest that although in vitro production was demonstrated, the elevations in concentration were nominal and less than 5 mg/L for all conditions tested over the 244-day period. These preliminary data suggest that urine samples should be preserved and stored at -20 degrees C to minimize artifactual GHB production. Most importantly, conditions of storage and preservative should also be taken into consideration when interpreting GHB results that are close to the administrative cutoff. In order to establish the distribution of GHB concentrations in routine forensic case samples, a series of 100 antemortem urine samples, in which GHB was not suspected, was analyzed. Samples were preserved with sodium fluoride (1%) and had been stored for up to one year at room temperature. Although concentrations as high as 7 mg/L were measured in some samples, the mean and median concentrations were 1.8 mg/L and 1.6 mg/L, respectively. Even following storage at room temperature for an extended period, more than 95% of the urine samples contained less than 5 mg/L GHB and 100% contained less than 10 mg/L. An administrative cutoff of 10 mg/L in antemortem urine was used for routine antemortem casework.

The synthetic cathinones are powerful psychostimulants that have been associated with impairment, intoxication and fatal overdose. Forensic laboratories must be able to identify these new drugs as part of antemortem and postmortem toxicology investigations. Preliminary reports have indicated that some of the synthetic cathinones are unstable in biological matrices. It is important to understand drug stability in biological evidence so that analytical findings can be interpreted appropriately. The objective of this study was to systematically evaluate the concentration, temperature and analyte-dependent stability of synthetic cathinones in preserved blood using liquid-chromatography/quadrupole-time of flight-mass spectrometry (LC/Q-TOF-MS). Cathinone stability was investigated at frozen, refrigerated, ambient and elevated temperature (-20°C, 4°C, 20°C and 32°C). Although no concentration dependent differences in stability were observed, cathinone stability was highly temperature and analyte-dependent. Substituents on the aromatic ring and nitrogen profoundly influenced stability. Tertiary amines (pyrrolidinyl analogs) were significantly more stable than their N-alkylated (secondary amine) counterparts. Furthermore, the methylenedioxy (MD) group also exerted a significant stabilizing effect, for both secondary and tertiary amines. The unsubstituted and ring-substituted secondary amines were the least stable, most notably 3-fluoromethcathinone (3-FMC). Under some conditions, significant losses were observed within hours of storage. Half-lives ranged from a little as 8 h (3-FMC) to 21 days (3,4-methylenedioxy-α-pyrrolidinobutiophenone, MDPBP) at elevated temperature (32°C). In contrast, half-lives ranged from 0.4 to >10 months when refrigerated and demonstrated even greater stability when frozen. Biological evidence may be subjected to a variety of environmental conditions prior to, and during transport to the laboratory. These findings highlight the need to consider the potential for both temperature and analyte-dependent differences. Due to the inherent instability of certain drugs within the class, quantitative drug findings in toxicological investigations must be interpreted with caution, and within the context of specimen storage and integrity.

No abstract

This report describes the outcomes of a process undertaken to review and update the National Safety Council's Alcohol, Drugs and Impairment Division's recommendations for the toxicological investigation of suspected alcohol and drug-impaired driving cases and motor vehicle fatalities. The updates to the recommendations are made based on a survey of practices in laboratories in the USA and Canada performing testing in these cases, consideration of existing epidemiological crash and arrest data, current drug use patterns, and practical considerations of widely available technology platforms in laboratories performing this work. The final recommendations updates are derived from a consensus meeting of experts recruited from survey respondents and the membership of the National Safety Council's Alcohol, Drug and Impairment Division. The principal changes in this round of recommendations include removal of butalbital, phenobarbital, and phencyclidine from Tier I (mandatory) to Tier II (optional) due to changes in prevalence. In addition, buprenorphine, fentanyl, tramadol, and their metabolites were moved from Tier II to Tier I due to increased prevalence and concerns about their potential for causing impairment. In addition, screening and confirmatory cutoffs for the oral fluid scope were further refined. Other additions were made to the list of Tier II compounds including fentanyl analogs (e.g., acetylfentanyl, butyrylfentanyl, furanylfentanyl, etc), mitragynine, novel opioids (e.g., MT-45, U-47700), atypical antipsychotics, and novel benzodiazepines (e.g., clonazolam, flubromazolam, etc).