Determination of Psychoactive Drugs in Air

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1		Kevin Honeychurch	+ 2154 word(s)	2154	2022-01-05 08:47:07	\|
2	FORMAT CHANGE	Jessie Wu	Meta information modification	2154	2022-02-22 09:42:22	\| \|
3	FORMAT CHANGE	Jessie Wu	-3 word(s)	2151	2022-02-22 09:44:31	\|

This entry is adapted from the peer-reviewed paper 10.3390/sci4010001

Understanding of the levels of psychoactive drugs in air is important for assessing both occupational and environmental exposure. Intelligence on the usage and manufacture of illegal drugs can also be gained. Environmental analysis and determination of air quality has recently expanded from its traditional focus to new pollutant categories that include illicit and psychoactive drugs.

air City Air Nitrous oxide (N2O) drugs cocaine THC fentanyl anaesthetic occupational exposure

1. Background

2. Air Pollution

2.1. Commercial Cannabis Farming Air Pollution

The aroma profiles generated for the cannabis plant were studied in the early 1970s ^[1]. More recently, Wang et al. ^[2] investigated effects of legal commercial cannabis cultivation in Denver, CO, USA on air quality. Reportedly, in 2018 in Denver county, there were over 600 registered cannabis cultivation facilities for recreational and medical use, mostly in commercial warehouses. The study focused on the determination of terpenes found in the headspace above cannabis plants. Reportedly, half of the total terpenes recorded across the state of Colorado were reported to be derived from Denver County alone. These increased terpene emissions from cannabis cultivation were calculated to result in an increase of up to 0.34 ppb in the hourly ozone concentrations during the morning and 0.67 ppb at night.

2.2. City Air

In one of the earliest studies focused on the levels of drugs in city air, Zaromb et al. ^[3] investigated the determination of airborne cocaine and heroin. Using a high-throughput liquid adsorption pre-concentration approach, air was sampled at 550–700 L/min r. The airborne drugs were isolated in either a 0.01 M sodium phosphate pH 7 buffer solution or a 0.01 M ortho-phosphoric acid solution of 0.1 g/l of Triton X-100, or in. Cocaine and heroin were quantified by liquid chromatography with electrochemical amperometric detection using a mobile phase of potassium phosphate buffer (pH 7–7.4, 0.02 M)-acetonitrile (40:60, v/v) at a flow rate of 1.0 mL/min, at a C₁₈ stationary phase. Electrochemical detection was undertaken at a glassy carbon electrode with an applied potential of +1.0 V (vs. Ag/AgCl).

Postigo et al. ^[4] investigated pressurised liquid extraction (PLE) for the extraction of atmospheric particles collected by high-volume air sampler using quartz microfiber filters. Analysis of the extracts was undertaken by liquid chromatography–tandem mass spectrometry employing selected reaction monitoring. The authors reported the presence of 17 different compounds, including cocaine and its derivatives, amphetamine and related compounds, opioids, cannabinoids and lysergic compounds. Quantitation was achieved utilising surrogated deuterated internal standards. Absolute recoveries were reported to be 50% with relative standard deviations of <13% reported for all compounds, except for the cannabinoids. The limits of determination were reported to range from 0.35 pg/m³ (for 2-oxo-3-hydroxy-LSD) to 22.55 pg/m³ (for 11-nor-9-carboxy-∆-9-tetrahydrocannabinol). The optimised procedure was applied to the analysis of ambient air samples collected from two urban background sites in the Spanish cities of Barcelona and Madrid. The majority of sites investigated were reported to show the presence of cocaine, benzoylecgonine, Δ9-tetrahydrocannabinol, ecstasy, amphetamine, methamphetamine, and heroin. The highest daily mean levels were reported for cocaine (850 pg/m³) and for heroin (143 pg/m³).

Cecinato et al. ^[5] investigated the occurrence of illicit substances in the air of five South American and six European cities. The analytical procedures required for the determination of cocaine, methadone and cocaethylene were optimised. Following Soxhlet extraction with subsequent column clean-up determination by GC/MS was found to be successful for the determination of these compounds at concentrations of ca. 1 pg/m³ in air for sample volumes of ca. 500 m³. Apart from the Algeria capital, Algiers, and the Serbian city, Pančevo, cocaine was reported present in all the cities investigated with concentrations ranging from pg to ng/m³ (Rome, Italy, 22 ± 97 pg/m³; Santiago, Chile, 2.2 ± 3.3 ng/m³). Reportedly the atmospheric concentrations of cocaine correlated to the prevalence of the drug in the Italian regions investigated. However, concentrations of methadone and cocaethylene in air were found to be always lower than the detection limit of the method. The method was reported to provide poor detection limits for cannabinoids, and it was concluded to be unsuitable for their determination, allowing only for the identification of cannabinol. Similar issues were highlighted for heroin (35 pg/m³); however, this compound was still quantifiable in airborne particulates from the city of Porto in Portugal. Air concentrations of cocaine collected during the winter from Bari, Rome, Milan and Taranto (right-hand y axis) were reported to be proportional with its prevalence, confiscations and crime numbers (left-hand y axis).

In a related investigation [40], it was shown that air cocaine concentrations correlated with the regional drug consumption in both Rome and Taranto. Studies of the total ion current chromatograms were able to show the presence of a numbers of drugs, including caffeine, nicotine, cocaine and cannabinol. The GC/MS analysis of carbonaceous aerosol samples showed levels of cocaine reaching >100 pg/m³ at some periods. However, the drug was reported to be virtually absent in Algiers (Algeria). Italian atmospheric cocaine concentrations were found to be similar to other pollutants, such as nitrated polyaromatic hydrocarbons or polychlorobiphenyls, but greater than those of polychlorodibenzo-p-dioxins/polychlorodibenzofurans. Cocaine was not found to correlate with the levels of air nicotine or caffeine levels, nor with the commonly studied air pollutant, benzo[α]pyrene. More notably, the levels of cocaine in the air of Rome and Taranto were reported to correlate with the amounts consumed or destroyed by the authorities in Italy. The authors highlighted airborne cocaine concentrations were in the same concentration range as many of the more commonly studied and recorded air pollutants.

3. Anaesthetic Gases Exposure to Health Care Workers

Table 1 summaries the analytical approaches and findings obtained for investigations in the exposure of anaesthetic drugs and gases. Nitrous oxide (N₂O), colloquially known as laughing gas or nitrous is commonly used as an anaesthetic, especially in surgery and dentistry. The application of N₂O by health care professionals, such as midwives, has been reported to result in air concentrations that can result in possibly dangerous levels. Investigation by Henderson et al. ^[6] showed that air levels of N₂O exceeded the legal occupational exposure standards for N₂O in 76% of midwives investigated. Midwives wore a passive sampling tube during the first four hours of their shift, placed within their breathing zone. This consisted of a steel tube packed with molecular sieve 5A with a diffusive cap on top. The levels of adsorbed N₂O were then determined by thermal desorption gas chromatography with electron capture detection.

Byhahn et al. ^[7] also investigated N₂O air exposure along with the anaesthetic gas sevoflurane. Their investigation used a similar approach, with a passive sampler placed in the breathing zone of paediatric surgeons, however, in this case, using a direct-reading photoacoustic infrared spectrometer. The study was undertaken in operating theatres equipped with waste anaesthetic gas scavengers and air conditioning. Results showed the surgeon and the anaesthesiologist to be exposed to low concentrations of both drugs. However, the concentrations found were below the threshold limits of 25 ppm for N₂O and 2 ppm for sevoflurane recommended by the National Institute of Occupational Safety and Health. Notably, exposure to sevoflurane and N₂O was reported to be higher during the surgery of young children compared to teenagers.

Further studies ^[8]^[9] have investigated possible occupational exposure to methoxyflurane by hospital emergency room nurses overseeing patients inhaling methoxyflurane. Methoxyflurane can be self-administered by patients using devices, such as the hand-held Penthrox ‘green whistle’ inhaler. Patients inhale vaporised liquid through the mouthpiece and then exhale this back into the device. Exhaled methoxyflurane is then captured in a chamber containing activated carbon. Despite the activated carbon chamber to capture exhaled methoxyflurane, it is possible that exposure to methoxyflurane vapour in the air could occur. A formal exposure limit of a maximum of 8-h TWA limit of 15 ppm had been set. However, the human odour detection threshold for methoxyflurane is very low, at 0.15 ppm and consequently, reports highlight the drug’s odour is frequently detectable ^[8]^[9]. As a result, there is a need to monitor staff exposure to methoxyflurane vapour and this has been undertaken in two investigations using passive personal monitoring devices based on activated charcoal in a hospital emergency department ^[8] and in bone marrow biopsy ^[9]. In one study, a 3M Organic Vapor Monitor 3500 badge sampler ^[10] was applied. These were extracted with the aid of ultrasonication for 10 min with carbon disulphide. Quantification of methoxyflurane was then undertaken by GC/MS using toluene as an internal standard. The lower limit of quantification was reported as 1 μg/sample. For 30 out of the 31 badge samplers investigated methoxyflurane concentrations were reported to be below the limit of quantification.

McAuliffe et al. ^[11] and Gold et al. ^[12] developed an LC/MS/MS based method to determine the airborne levels of fentanyl and propofol in the air present in a hospital operation theatre. Aerosolized fentanyl was reported to be detectable in air sampled from the cardiothoracic operating room in a number of areas. These included the patients’ expiratory circuits, headspace above the sharps’ disposal bins, but reportedly, not in the air of adjoining hallways. Aerosolized propofol was reported to be detected in the exhaled air of a patient undergoing prostate surgery. Fentanyl was extracted from air samples collected in 500 mL glass bottles containing 50 mL of methanol. Samples were taken from the hospital cardiovascular surgery suite and its adjacent hallway, from the air outside and from a separate building. The bottles containing the sampled air and methanol were put in a shaker for 20 min. The methanol extract was then evapourated and the resulting residue reconstituted in 1 mL of water. The resulting extract was then subjected to solid-phase extraction (SPE) and the resulting eluate evaporated and reconstituted for liquid chromatography/mass spectrometry, using multiple reaction monitoring (m/z 337.4 → 188.4 transition). Chromatographic separation was undertaken using a mobile phase of 70% acetonitrile–water with 0.1% formic acid at a flow rate of 400 µL/min. The authors also examined exhaled breath from patients undergoing prostate surgery using propofol as an anaesthetic collected in 2 L Teflon environmental collection bags. The specimens were acquired at time points between 5 and 30 min following the intravenous administration of propofol, with a baseline measurement taken beforehand. The exhaled breath specimens were analysed using solid-phase microextraction (SPME) and GC/MS. Propofol was reported not to be detectable in the baseline specimen, but was recorded in each exhaled breath samples examined taken during propofol infusion.

Air concentrations of the anaesthetics, isoflurane and sevoflurane in Brazilian hospital operating rooms were investigated by Braz et al. ^[13]. Operating rooms without active waste air scavenging systems were found to be associated with adverse health effects. Infrared spectroscopic investigations of air concentrations of isoflurane and sevoflurane were undertaken from the respiratory area of the anaesthesiologist and the assistant nurse and at the anaesthesia station at 12 and 30 min following the start of surgery. In un-scavenged operating rooms, air concentrations of isoflurane and sevoflurane were reported to be higher than the US recommended limit of 2 ppm. In the scavenged operating rooms investigated, the average concentrations of isoflurane were reported to be below the US exposure limit, apart for the measurements obtained near the anaesthesia station. However, sevoflurane, concentrations exceeded the limit value at measurement locations and at both times. The exposure to both anaesthetics exceeded the international limit in un-scavenged operating rooms.

Table 1. Determination of anaesthetic gas and drugs in air.

Drug(s) Determined	Sample	Extraction	Column, Mobile Phase/Temperature Program	Detector	Limit of Detection	Comments	Ref.
N₂O.	Passive sampling tube placed within the breathing zone, packed with molecular sieve 5A.	Thermal desorption	Gas chromatography. HP Plot Q, 30 m × 0.53 mm ID column. Isothermal 30 °C.	Electron capture detection		Air samples in 76% of midwife shifts exceeded occupational exposure standards.	^[6]
N₂O and sevoflurane.	Passive sampler placed in the breathing zone of paediatric surgeons.					Concentrations below the threshold limits.	^[7]
Methoxyflurane.	Occupational exposure by nurses in emergency room and in bone marrow biopsy procedures, using a 3M Organic Vapor Monitor 3500 badge sampler.	Badge samplers extracted in carbon disulphide with ultrasound.	Gas chromatography.	Mass spectrometry, using toluene as an internal standard.	The lower limit of quantification was 1.0 μg/sample.	Concentrations below the limit of quantification in 30 of 31 badge samplers investigated.	^[8]^[9]
Propofol and fentanyl.	Air samples collected in hospital operating theatres.	SPE, following solvent extraction with methanol of air sample for fentanyl. SPME extraction for Propofol.	LC/MS/MS. Multiple reaction monitoring mode m/z 337.4 →188.4 for fentanyl. Xterra C₈ column (3.0 ×·250 mm, 5µm), guard column. Mobile phase: acetonitrile–water 0.1% formic acid (70:30), 400 µL/min.		Qualitative.	Air samples from operating theatre were positive for fentanyl. Samples taken outside theatre were negative. Sample of patient’s breath positive for propofol. Others reported negative.	^[11]^[12]
Isoflurane and sevoflurane.	Brazilian hospital operating rooms.			Infrared spectroscopy.		Exposure to both anaesthetics exceeded the international limit in the air of un-scavenged operating rooms.	^[13]

References

Hood, L.V.S.; Dames, M.E.; Barry, G.T. Headspace Volatiles of Marijuana. Nature 1973, 242, 402–403.
Wang, T.C.; Wiedinmyer, C.; Ashworth, K.; Harley, P.C.; Ortega, J.; Rasool, Q.Z.; Vizuete, W. Potential regional air quality impacts of cannabis cultivation facilities in Denver, Colorado. Atmos. Chem. Phys. 2019, 19, 13973–13987.
Zaromb, S.; Alcaraz, J.; Lawson, D.; Woo, C.S. Detection of airborne cocaine and heroin by high-throughput liquid-absorption preconcentration and liquid chromatography-electrochemical detection. J. Chromatogr. 1993, 643, 107–115.
Postigo, C.; de Lopez Alda, M.J.; Mar, V.; Querol, X.; Alastuey, A.; Artiñano, B.; Barceló, D. Determination of Drugs of Abuse in Airborne Particles by Pressurized Liquid Extraction and Liquid Chromatography-Electrospray-Tandem Mass Spectrometry. Anal. Chem. 2009, 81, 4382–4388.
Cecinato, A.; Balducci, C.; Nervegna, G. Occurrence of cocaine in the air of the World’s cities An emerging problem? A new tool to investigate the social incidence of drugs? Sci. Total Envrion. 2009, 40, 1683–1690.
Cecinato, A.; Balducci, C. Detection of cocaine in the airborne particles of the Italian cities Rome and Taranto. J. Sep. Sci. 2007, 30, 1930–1935.
Henderson, K.A.; Matthews, I.P.; Adisesh, A.; Hutchings, A.D. Occupational exposure of midwives to nitrous oxide on delivery suites. Occup. Environ, Med. 2003, 60, 958–961.
Byhahn, C.; Heller, K.; Lischke, V.; Westphal, K. Surgeon’s Occupational Exposure to Nitrous Oxide and Sevoflurane during Pediatric Surgery. World J. Surg. 2001, 25, 1109–1112.
Frangos, J.; Belbachir, A.; Dautheville, S.; Jung, C.; Herklotz, K.; Amon, F.; Dickerson, S.; Chomier, B. Non-interventional study evaluating exposure to inhaled, low-dose methoxyflurane experienced by hospital emergency department personnel in France. BMJ Open 2020, 10, e034647.
Ruff, R.; Kerr, S.; Kerr, D.; Zalcberg, D.; Stevens, J. Occupational exposure to methoxyflurane administered for procedural sedation: An observational study of 40 exposures. Br. J. Anaesth. 2018, 120, 1435–1437.
3M Air Monitoring Guide: User Instructions 3500/3510, 3520/3530, 3550/3551. Available online: https://multimedia.3m.com/mws/media/1558692O/3m-air-monitoring-guide-3500-series-user-instructions.pdf (accessed on 25 January 2021).
McAuliffe, P.F.; Gold, M.S.; Bajpai, L.; Merves, M.L.; Frost-Pineda, K.; Pomm, R.M.; Goldberger, B.A.; Melker, R.J.; Cendan, J.C. Second-hand exposure to aerosolized intravenous anesthetics propofol and fentanyl may cause sensitization and subsequent opiate addiction among anesthesiologists and surgeons. Med. Hypotheses 2006, 66, 874–882.
Gold, M.S.; Melker, R.J.; Dennis, D.M.; Morey, T.E.; Bajpai, L.K.; Pomm, R.; Frost-Pineda, K. Fentanyl Abuse and Dependence. J. Addict. Dis. 2006, 25, 15–21.
Braz, L.G.; Braz, J.R.C.; Cavalcante, G.A.S.; Souza, K.M.L.; Mariana, M.C.L.; Braz, G. Comparação de resíduos de gases anestésicos em salas de operação com ou sem sistema de exaustão em hospital universitário brasileiro. Rev. Bras. Anestesiol. 2017, 67, 516–520.

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