A multi-laboratory investigation of drug background levels.

Identifying and quantifying the drug background in operational environments such as forensic laboratories is an emerging body of research. Knowing these levels is crucial to addressing issues like occupational exposure risk - due to the emergence of potent novel psychoactive substances and synthetic opioids - and data integrity - due to improvements in instrument sensitivity. The work presented here builds upon a prior study to provide a broader representation of the average drug background levels found on surfaces in forensic laboratories. Over 700 samples from 20 laboratories were collected, extracted, and analyzed quantitatively using LC-MS/MS, and qualitatively using TD-DART-MS. Quantitative analysis by LC-MS/MS included a panel of 18 drugs while the non-targeted qualitative analysis by TD-DART-MS screened for over three hundred drugs and excipients. The study focused primarily on surfaces within the drug unit and evidence receiving area of the laboratories, but also investigated other operational units (crime scene, drug interdiction, latent prints, and toxicology) as well as report writing. Background levels were highest within the drug unit of the laboratory, though detectable (tens of nanograms) levels were observed in nearly all sampled areas. The data from this expanded study plays a critical role in addressing laboratory concerns such as establishing drug identification reporting limits for new instrumentation and establishing new workflow or cleaning protocols while also providing a more comprehensive dataset for general environmental background studies.

A snapshot of drug background levels on surfaces in a forensic laboratory.

While background studies have been commonplace in many occupational fields for a long time, attempts to understand the chemical background in forensics labs has been largely understudied. Such studies can help define the efficiency of cleaning procedures and the integrity of collected data, which is becoming increasingly important due to improving sensitivity of instrumentation and the prevalence with which potent drugs of abuse, such as the opioids, are being seen. The results from this study provide a snapshot of the drug background levels on surfaces in a laboratory system comprised of a central laboratory and two satellite laboratories. Samples were collected from work surfaces by swiping with meta-aramid wipes, and extracted for analysis by LC/MS/MS, for quantitation, and TD-DART-MS, for non-targeted screening. Surfaces were sampled from within the drug unit (where drug evidence is processed) and the evidence receiving unit (where drug cases are handled) in all laboratories as well as the report writing area, the toxicology unit and the crime scene unit in the central laboratory. Results showed that the background was restricted primarily to the benches, balances, and instrumentation within the drug unit - with approximately an order of magnitude higher concentrations observed on the balances, compared to the benches. Higher levels were also observed in analyst specific surfaces when compared to general use surfaces within the drug unit - which corresponded to where bulk evidence handling was completed. Background in the evidence receiving and report writing sections was minimal. Comparison of the main laboratory to the satellite laboratories showed similarities amongst frequently encountered drugs like cocaine, but noticeable differences in opioids which could be attributed to differences in the make-up of exhibits each laboratory receives. Understanding the background levels of drugs in a forensic laboratory environment is crucial to improving cleaning protocols, helping define detection limits for highly sensitive analyses, and providing additional results to the broader community that has been establishing background levels in other environments.

Quantifying the stability of trace explosives under different environmental conditions using electrospray ionization mass spectrometry.

This work investigates the stability of trace (tens of nanograms) deposits of six explosives: erythritol tetranitrate (ETN), pentaerythritol tetranitrate (PETN), cyclotrimethylenetrinitramine (RDX), cyclotetramethylenetetranitramine (HMX), 2,4,6-trinitrotoluene (TNT), and 2,4,6-trinitrophenylmethylnitramine (tetryl) to determine environmental stabilities and lifetimes of trace level materials. Explosives were inkjet printed directly onto substrates and exposed to one of seven environmental conditions (Laboratory, -4°C, 30°C, 47°C, 90% relative humidity, UV light, and ozone) up to 42 days. Throughout the study, samples were extracted and quantified using electrospray ionization mass spectrometry (ESI-MS) to determine the stability of the explosive as a function of time and environmental exposure. Statistical models were then fit to the data and used for pairwise comparisons of the environments. Stability was found to be exposure and compound dependent with minimal sample losses observed for HMX, RDX, and PETN while substantial and rapid losses were observed in all conditions except -4°C for ETN and TNT and in all conditions for tetryl. The results of this work highlight the potential fate of explosive traces when exposed to various environments.

Ion mobility spectrometry nuisance alarm threshold analysis for illicit narcotics based on environmental background and a ROC-curve approach.

The discriminative potential of an ion mobility spectrometer (IMS) for trace detection of illicit narcotics relative to environmental background was investigated with a receiver operating characteristic (ROC) curve framework. The IMS response of cocaine, heroin, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and Δ(9)-tetrahydro-cannabinol (THC) was evaluated against environmental background levels derived from the screening of incoming delivery vehicles at a federal facility. Over 20 000 samples were collected over a multiyear period under two distinct sets of instrument operating conditions, a baseline mode and an increased desorption/drift tube temperature and sampling time mode. ROC curves provided a quantifiable representation of the interplay between sensitivity (true positive rate, TPR) and specificity (1 - false positive rate, FPR). A TPR of 90% and minimized FPR were targeted as the detection limits of IMS for the selected narcotics. MDMA, THC, and cocaine demonstrated single nanogram sensitivity at 90% TPR and <10% FPR, with improvements to both MDMA and cocaine in the elevated temperature/increased sampling mode. Detection limits in the tens of nanograms with poor specificity (FPR ≈ 20%) were observed for methamphetamine and heroin under baseline conditions. However, elevating the temperature reduced the background in the methamphetamine window, drastically improving its response (90% TPR and 3.8% FPR at 1 ng). On the contrary, the altered mode conditions increased the level of background for THC and heroin, partially offsetting observed enhancements to desorption. The presented framework demonstrated the significant effect environmental background distributions have on sensitivity and specificity.

Particle Fabrication Using Inkjet Printing onto Hydrophobic Surfaces for Optimization and Calibration of Trace Contraband Detection Sensors.

A method has been developed to fabricate patterned arrays of micrometer-sized monodisperse solid particles of ammonium nitrate on hydrophobic silicon surfaces using inkjet printing. The method relies on dispensing one or more microdrops of a concentrated aqueous ammonium nitrate solution from a drop-on-demand (DOD) inkjet printer at specific locations on a silicon substrate rendered hydrophobic by a perfluorodecytrichlorosilane monolayer coating. The deposited liquid droplets form into the shape of a spherical shaped cap; during the evaporation process, a deposited liquid droplet maintains this geometry until it forms a solid micrometer sized particle. Arrays of solid particles are obtained by sequential translation of the printer stage. The use of DOD inkjet printing for fabrication of discrete particle arrays allows for precise control of particle characteristics (mass, diameter and height), as well as the particle number and spatial distribution on the substrate. The final mass of an individual particle is precisely determined by using gravimetric measurement of the average mass of solution ejected per microdrop. The primary application of this method is fabrication of test materials for the evaluation of spatially-resolved optical and mass spectrometry based sensors used for detecting particle residues of contraband materials, such as explosives or narcotics.

Quantifying the degradation of TNT and RDX in a saline environment with and without UV-exposure.

Terrorist attacks in a maritime setting, such as the bombing of the USS Cole in 2000, or the detection of underwater mines, require the development of proper protocols to collect and analyse explosive material from a marine environment. In addition to proper analysis of the explosive material, protocols must also consider the exposure of the material to potentially deleterious elements, such as UV light and salinity, time spent in the environment, and time between storage and analysis. To understand how traditional explosives would be affected by such conditions, saline solutions of explosives were exposed to natural and artificial sunlight. Degradation of the explosives over time was then quantified using negative chemical ionization gas chromatography mass spectrometry (GC/NCI-MS). Two explosives, trinitrotoluene (TNT) and cyclotrimethylenetrinitramine (RDX), were exposed to different aqueous environments and light exposures with salinities ranging from freshwater to twice the salinity of ocean water. Solutions were then aged for up to 6 months to simulate different conditions the explosives may be recovered from. Salinity was found to have a negligible impact on the degradation of both RDX and TNT. RDX was stable in solutions of all salinities while TNT solutions degraded regardless of salinity. Solutions of varying salinities were also exposed to UV light, where accelerated degradation was seen for both explosives. Potential degradation products of TNT were identified using electrospray ionization mass spectrometry (ESI-MS), and correspond to proposed degradation products discussed in previously published works [1].

Optimized thermal desorption for improved sensitivity in trace explosives detection by ion mobility spectrometry.

In this work we evaluate the influence of thermal desorber temperature on the analytical response of a swipe-based thermal desorption ion mobility spectrometer (IMS) for detection of trace explosives. IMS response for several common high explosives ranging from 0.1 ng to 100 ng was measured over a thermal desorber temperature range from 60 °C to 280 °C. Most of the explosives examined demonstrated a well-defined maximum IMS signal response at a temperature slightly below the melting point. Optimal temperatures, giving the highest IMS peak intensity, were 80 °C for trinitrotoluene (TNT), 100 °C for pentaerythritol tetranitrate (PETN), 160 °C for cyclotrimethylenetrinitramine (RDX) and 200 °C for cyclotetramethylenetetranitramine (HMX). By modifying the desorber temperature, we were able to increase cumulative IMS signal by a factor of 5 for TNT and HMX, and by a factor of 10 for RDX and PETN. Similar signal enhancements were observed for the same compounds formulated as plastic-bonded explosives (Composition 4 (C-4), Detasheet, and Semtex). In addition, mixtures of the explosives exhibited similar enhancements in analyte peak intensities. The increases in sensitivity were obtained at the expense of increased analysis times of up to 20 seconds. A slow sample heating rate as well as slower vapor-phase analyte introduction rate caused by low-temperature desorption enhanced the analytical sensitivity of individual explosives, plastic-bonded explosives, and explosives mixtures by IMS. Several possible mechanisms that can affect IMS signal response were investigated such as thermal degradation of the analytes, ionization efficiency, competitive ionization from background, and aerosol emission.

Application of inkjet printing technology to produce test materials of 1,3,5-trinitro-1,3,5 triazcyclohexane for trace explosive analysis.

The feasibility of the use of piezoelectric drop-on-demand inkjet printing to prepare test materials for trace explosive analysis is demonstrated. RDX (1,3,5-trinitro-1,3,5 triazcyclohexane) was formulated into inkjet printable solutions and jetted onto substrates suitable for calibration of the ion mobility spectrometry (IMS) instruments currently deployed worldwide for contraband screening. Gravimetric analysis, gas chromatography/mass spectrometry (GC/MS), and ultraviolet-visible (UV-vis) absorption spectroscopy were used to verify inkjet printer solution concentrations and the quantity of explosive dispensed onto test materials. Reproducibility of the inkjet printing process for mass deposition of the explosive RDX (1,3,5-trinitro-1,3,5 triazcyclohexane) was determined to be better than 2% for a single day of printing and better than 3% day-to-day.

Effect of permeation enhancers on buccal absorption.

This paper reports an investigation on matrices based on the mucoadhesive polymers hydroxypropylmethylcellulose and sodium alginate, intended for sublingual administration of 1 mg lorazepam (LZ, 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one, CAS 846-49-1). The effect of different amounts of three permeation enhancers, cetylpyridinium chloride (CPC), polyethoxylated castor oil (PCO) and polyethylene glycol dodecyl ether (PGDE) on LZ permeation from the matrices was investigated using three models: (a) cultured monolayer of human buccal epithelial cells; (b) hamster cheek pouch mucosa in vitro, and (c) buccal administration to rabbits in vivo. In the first two models the presence of promoters, except when present at the higher concentrations, increased the drug permeation rate. The permeation-reducing effect was rationalized on the basis of micellar complexation of the drug. In the living rabbit (c) model, only CPC at the highest tested concentration was moderately active, while in the cultured cell model activity differences among the enhancers were less evident. Different effects of the promoters in the ex vivo and in vivo models were tentatively explained on the basis of the structural characteristics of the absorbing membranes. The present study, while confirming the efficacy of CPC as promoter in models involving biological membranes, does not provide conclusive data on the validity of the cultured cells model for assessment of buccal drug absorption.