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Review

Detection of Cannabinoids in Oral Fluid Specimens as the Preferred Biological Matrix for a Point-of-Care Biosensor Diagnostic Device

1
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Faculty of Engineering Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
2
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel
3
Department of Postharvest Science of Fresh Fruit, Volcani Center, Agricultural Research Organization, Rishon LeZion 7505101, Israel
4
Chulabhorn International College of Medicine, Thammasat University, Klong Luang 12120, Pathum Thani, Thailand
5
Center of Excellence in Modern Technology and Advanced Manufacturing for Medical Innovation, Thammasat University, Klong Luang 12120, Pathum Thani, Thailand
6
Department of Materials and Textile Technology, Faculty of Science and Technology, Thammasat University, Klong Luang 12120, Pathum Thani, Thailand
7
The Ilse Katz Center for Meso and Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biosensors 2024, 14(3), 126; https://doi.org/10.3390/bios14030126
Submission received: 23 January 2024 / Revised: 18 February 2024 / Accepted: 21 February 2024 / Published: 27 February 2024
(This article belongs to the Special Issue Feature Review Papers for Biosensors)

Abstract

:
An increasing number of countries have started to decriminalize or legalize the consumption of cannabis for recreational and medical purposes. The active ingredients in cannabis, termed cannabinoids, affect multiple functions in the human body, including coordination, motor skills, memory, response time to external stimuli, and even judgment. Cannabinoids are a unique class of terpeno-phenolic compounds, with 120 molecules discovered so far. There are certain situations when people under the influence of cannabis may be a risk to themselves or the public safety. Over the past two decades, there has been a growing research interest in detecting cannabinoids from various biological matrices. There is a need to develop a rapid, accurate, and reliable method of detecting cannabinoids in oral fluid as it can reveal the recent intake in comparison with urine specimens, which only show a history of consumption. Significant improvements are continuously made in the analytical formats of various technologies, mainly concerning improving their sensitivity, miniaturization, and making them more user-friendly. Additionally, sample collection and pretreatment have been extensively studied, and specific devices for collecting oral fluid specimens have been perfected to allow rapid and effective sample collection. This review presents the recent findings regarding the use of oral fluid specimens as the preferred biological matrix for cannabinoid detection in a point-of-care biosensor diagnostic device. A critical review is presented, discussing the findings from a collection of review and research articles, as well as publicly available data from companies that manufacture oral fluid screening devices. Firstly, the various conventional methods used to detect cannabinoids in biological matrices are presented. Secondly, the detection of cannabinoids using point-of-care biosensors is discussed, emphasizing oral fluid specimens. This review presents the current pressing technological challenges and highlights the gaps where new technological solutions can be implemented.

1. Introduction

1.1. Why Is It Important to Perform Cannabinoids Detection?

An increasing number of countries have started to decriminalize or legalize the consumption of cannabis for recreational and medical purposes [1,2,3]. The active ingredients in cannabis affect multiple functions in the human body, including coordination, motor skills, memory, response time to external stimuli, and even judgment [4,5,6]. Therefore, there are certain situations when people under the influence of cannabis may be a risk to themselves or the public safety. Such situations include, for example, during driving, while operating heavy machinery, in specific workplace settings, in the army, in rehab programs for overcoming addictions, and during parental custody [7,8]. Over the past two decades, there has been a growing research interest in the detection of cannabinoids from various biological matrices with the need to develop a rapid, accurate, and reliable method of detecting cannabinoids in oral fluid (Figure 1), as it can reveal the recent intake in comparison with urine specimens, which only shows a history of consumption [9,10].

1.2. Different Types of Cannabinoids

Cannabinoids are a unique class of terpeno-phenolic compounds [11], with 120 molecules discovered so far [12]. They have been extensively studied after the initial discovery of Δ9-tetrahydrocannabinol (THC), which is the main compound responsible for the psychoactive effect of cannabis inebriation [13,14,15]. Based on the chemical formulas of cannabinoids, 11 subclasses have been distinguished. Besides THC, particular importance is also given to cannabidiol (CBD), which does not produce any psychedelic effects [16]. CBD is commonly used to treat various medical conditions in the human body [5,17,18,19,20,21,22,23,24,25,26,27,28,29,30]. In addition to THC and CBD, several other cannabinoids have already been identified as having medicinal properties (e.g., tetrahydrocannabivarin (THCV), cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN)) [31]. Other types of cannabinoids include the endocannabinoids that are produced in the human body (e.g., anandamide, 2AG) [32], which regulate a vast number of physiological functions, such as the immune responses, cognition, emotions, motor coordination, body temperature, and sleep/wake cycle [32,33,34].

1.3. Preferred Cannabinoids as Targets for Detection

THC is still the most well-studied cannabinoid. In 1974, Edward R. Garrett et al. initially investigated the physico-chemical properties, bonding capabilities, adherence to different materials, and solubility of THC [35]. The reported solubility of THC in water is 2.8 mg/L, while in a saline solution (0.15 M NaCl), it is lower, at 0.77 mg/L, at a temperature of 23 °C. Different organic solvents affect the solubility of THC while also providing good stability, especially in the extraction process. Other findings report the adherence of THC to glass, in a proportion of 20–40%, based on its concentration in an aqueous-ethanol solution (0.1–0.05 µg/mL) and the contact surface. In contrast, the adherence of THC to plastic and rubber caps that were used to seal the plastic tubes ranged between 70–97%. In order to remove or reduce the adherence of THC to these materials, the sample can be first pretreated with silyl. Most importantly, the study showed that THC had a high rate of protein binding of up to 97%, which was not dependent on its concentration [35]. It was previously reported that once THC reaches the bloodstream, it binds proteins, and as a result, it is transported to various tissues and organs [36]. Once the THC reaches the blood, only a small portion remains free after it is rapidly absorbed into adipose tissues, and then it is released gradually over time [37]. It is known that THC is rapidly degraded in an acidic solution; therefore, if it is administered orally, it is degraded in the stomach, and only a small portion is bio-available, as compared to smoked or vaporized administration [38].

1.4. Existing Challenges in the Detection of Cannabinoids

Significant improvements are continuously made in the analytical formats of various technologies, mostly concerning improving their sensitivity and miniaturization and making them more user-friendly [39]. Additionally, sample collection and pretreatment have been extensively studied, and specific devices for collecting oral fluid specimens have been perfected to allow rapid and effective sample collection [40]. The main challenge that is increasingly discussed is the influence of the interactions between different cannabinoids and with different substrates and materials, primarily THC as the most studied cannabinoid. For example, it has been previously shown that THC interacts with plastic containers [35], making the extraction of cannabinoids from collection devices a challenging process, especially without the use of buffers. This implies that the use of certain analytical procedures is currently limited and that more research should be conducted in order to evaluate any possible errors due to the potential loss of THC. Moreover, efforts are being made to improve the interpretation of the results to allow a more accurate evaluation [41]. The interpretation of results is a crucial step for detecting the actual levels of cannabinoids in the human body, which further leads to better decision-making processes by the authorities. The pressing current challenge is to develop a diagnostic technology that demonstrates high sensitivity and specificity and, ideally, does not need chemicals in the sample preparation process. This review presents the recent findings regarding the use of oral fluid specimens as the preferred biological matrix for cannabinoid detection in a point-of-care biosensor diagnostic device. A critical review is presented, discussing the findings from a collection of review and research articles, as well as publicly available data from companies that manufacture oral fluid screening devices. Firstly, the various conventional methods used to detect cannabinoids in biological matrices are presented. Secondly, the detection of cannabinoids using point-of-care biosensors is discussed, emphasizing oral fluid specimens. This review presents the current pressing technological challenges and highlights the gaps where new technological solutions can be implemented.

2. Detection of Cannabinoids

Figure 2 shows the detection of cannabis from oral fluid specimens. These techniques require multiple steps in traditional protocols, including specimen collection, stabilization, extraction, screening analysis, confirmation, and interpretation of results. Efforts are taken to simplify the procedure, such as simultaneous stabilization and extraction. Chromatographic procedures such as GC-MS, LC-MS, and HPLC-MS are considered the gold standard due to their precision and quantitative capabilities. Immunoassays, notably ELISA and EIA, are very sensitive but produce qualitative results that require extra validation steps. Electrochemical sensors are gaining popularity for point-of-care testing due to their portability and quick findings. However, they are still under development and have issues with selectivity and integration into user-friendly equipment.

2.1. Conventional Detection Procedure

The analytical detection method must be validated, well-known, and accepted as a standard diagnostic device. In the case of detection of cannabinoids in biological matrices, for example, oral fluid specimens, certain steps must be followed: (1) collection of the biological specimen; (2) stabilization of the cannabinoids in buffers; (3) extraction of the cannabinoids from the collection device; (4) screening analysis of the extract; (5) confirmation analysis with quantification of the cannabinoids; and (6) the interpretation of the results. Despite the importance of each step, in order to expedite the process of detecting cannabinoids, fewer steps should be defined. For example, the stabilization and extraction of cannabinoids in the buffer can be conducted in parallel in the collection device. An additional contribution to the long detection process of cannabinoids is the need to send a second sample for validation to a centered lab after a positive result is detected. However, this process is time-consuming and requires collecting a second sample that can differ from the first one, especially when quantitation is required. Several conventional techniques are currently used for the detection of cannabinoids (Table 1), which can be categorized into either chromatographic methods or immunoassays. Additional methods include electrochemistry and capillary electrophoresis, but these techniques are still mostly research-based [42,43]. The gold standard lab-based methods for cannabinoid detection are based on chromatography. These include gas chromatography coupled with mass spectrometry (GC-MS), liquid chromatography coupled with mass spectrometry (LC-MS), and high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS), which can also be coupled with MS for improved detection (HPLC-MS-MS) [44]. These techniques are extremely specific, sensitive, and quantitative. Not only that, but these techniques can analyze various biological matrices for cannabinoid detection with great accuracy. They must also be used in order to validate the results that are obtained by an on-site testing device.

2.2. Immunoassays in Point-of-Care Biosensors

The most common method for the detection of cannabinoids in oral fluid specimens is immunoassay screening [45]. This offers a promising approach for point-of-care detection of cannabinoids in oral fluid due to its high specificity, sensitivity, and potential for rapid results. These assays rely on the specific binding of antibodies to target molecules, such as THC and its metabolites [46]. In the context of cannabinoid detection, an antibody specific to the target cannabinoid (THC, THC-COOH, and CBD) is immobilized on a solid support [47]. The oral fluid sample is then introduced, allowing cannabinoids to bind to the immobilized antibody. Unbound material is washed away, and a secondary antibody labeled with a detectable signal (e.g., enzyme, fluorescent molecule) is introduced [48]. This secondary antibody binds to the first antibody if the target cannabinoid is present, creating a signal proportional to the quantity of bound cannabinoids. The intensity of this signal, measured visually or electronically, allows for qualitative or quantitative detection of cannabinoids in oral fluid. These techniques are widespread and widely used in a variety of domains. In the lab, enzyme-linked immunosorbent assay (ELISA) [45] or enzyme immunoassay (EIA) [49] are used in order to detect cannabinoids with good sensitivity and specificity. They have the advantage of being easily modified for lateral flow immunoassay, thus allowing them to be used on-site as point-of-care devices [40]. The benefits of point-of-care biosensors include accessibility, portability, robust setup, rapid detection procedure, and ease of use by non-expert personnel. Immunoassays are based on the formation of immunocomplexes that are conjugated to signaling particles after the analyte of interest binds to the specific antibodies in the test, and a measurable signal is produced (e.g., colorimetric or fluorescent) [50]. Various approaches are used in order to improve the sensitivity of the immunoassays, for example, by color enhancement, amplification of the immunocomplex response, or by developing new signaling nanoparticles [48]. Several different types of readers have been developed for the improved interpretation of the detection lines. They are based on projecting light at certain wavelengths on the test strip and then collecting the reflectance of the reporting particles by photodiodes, which convert the photon emission into a digital signal [51]. Another more popular technique is the use of simple cameras, even from a smartphone, to interpret the color intensity of the strip lines [52]. The existing immunoassays are effective but still have disadvantages [45]. Most importantly, these methods are not fully quantitative, with only a few achieving semi-quantitation [53], for example, after identifying a THC cut-off of 4 ng/mL [54], allowing detection in the range of 4–200 ng/mL [55]. Another significant disadvantage is the need for an additional sample collection device, where the sample is usually diluted in special buffers in order to improve stability and eliminate unspecific binding of THC to plastic or glass surfaces [56,57]. This method does not allow the reuse of the same sample for multiple testing; thus, two samples need to be collected, one for the on-site screening and another to be later sent to the laboratory for validation. In addition, another important aspect that must be considered is the need for an analytical device capable of detecting small molecules as the test target analyte, which is a challenge in developing new technologies.

2.3. Electrochemical Sensors for Point-of-Care Testing

While immunoassays remain the most used POCT technique for the detection of cannabinoids in oral fluid, there is a growing interest in exploring electrochemical sensors due to their effectiveness, portability, and rapid results [58]. The specific details may vary depending on the type of sensor, yet the general principle of how most electrochemical sensors work for cannabinoid detection in oral fluid involves several steps: (1) capturing the analyte on a sensor chip which has a modified surface with a recognition element, such as an aptamer or antibody, specifically designed to bind to the target cannabinoid molecule present in the oral fluid sample; (2) interaction, where cannabinoids come into contact with the sensor chip, and the target molecule binds to the recognition element on its surface; (3) signal generation, when the binding event alters the electrical properties of the sensor surface in different ways, determining a change in the conductivity, resistance, or difference of electrical potential; (4) measurement and analysis, where the sensor measures the resulting change in electrical properties (conductivity, resistance, or current) and converts it into a digital signal, which is then analyzed by an electronic device to determine the presence and concentration of the target cannabinoids; and (5) output, where the analysis software interprets the signal and provides information about the presence and concentration of the cannabinoids. Several types of electrochemical sensors have been researched for the detection of cannabinoids in oral fluid, with the use of aptamers or nanoparticles, conductometric, and impedimetric sensors [59]. They all hold promise for POC cannabinoid detection, but they are still under development and face challenges like selectivity, sensitivity, and integration into user-friendly devices. Aptamers and nanoparticle-based sensors show potential but require further research and optimization for oral fluid applications [60,61]. Conductometric and impedimetric sensors are simpler but face limitations in specificity and require miniaturization for POC suitability [62,63]. To date, there are no commercially available electrochemical sensors specifically designed for cannabinoid detection in oral fluid. While research and development in this area are active, these sensors have not yet received regulatory approval and widespread market adoption for POC testing.

3. Biological Matrices for the Detection of Cannabinoids

3.1. Various Biological Matrices, including Blood and Urine Specimens

Various biological matrices are used for the detection of cannabinoids, with the choice between them being dependent on the required application (Table 2). Several factors are taken into consideration before choosing the biological matrix, including the applied analytical method [41,44,64], its sensitivity, the amount of sample required for analysis, the time range for detection [65], the time since the latest cannabinoid consumption, the availability of the matrix, and the need for analysis at point-of-care or in a central lab. In the latter case, a collection device is also required, which includes buffers for stabilization [40,56,66]. Different biological matrices have different characteristics. Blood is considered the reference standard biological matrix because it shows the analyte levels in the internal general circulation and allows the derivation of correlations between its quantity and the levels of impairment as well as the time period since the latest usage [67,68]. Moreover, the analytical methods used to detect cannabinoids in the blood are validated without discrepancies between laboratories [39]. However, the blood sample collection requires trained personnel and is invasive; therefore, it can be unpleasant for the subject. It is also possible that the donor will refuse to provide his blood sample. Urine is one of the biological matrices that has been heavily researched [65,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92]. The analytical methods for the detection of cannabinoids in urine samples have also been validated and have good sensitivity and specificity; however, the screening of cannabinoids in urine samples is limited to THC-COOH, which is a metabolite that is created after the enzymatic degradation of THC [93,94]. Another disadvantage of the use of urine samples is that it is not a good indicator of recent cannabis intake but rather only of the history of usage. A urine sample is considered to be relatively easy to collect from the subject, even though it requires a special room, and for the collector personnel to be of the same sex in order to protect the privacy of the subject and also to eliminate the existing risk of matrix adulteration. Other biological matrices include hair, sweat, and even nails; however, only a few analytical methods have been developed for the detection of cannabinoids in these types of specimens [37]. These biological matrices are mainly useful in detecting the history of cannabinoid use because they do not show the recent intake or the last time of consumption, meaning they are not suitable for point-of-care [50]. Moreover, they are often not used for the detection of cannabinoids because they are exposed and, therefore, can be easily contaminated by the environment, which requires a long and difficult sample preparation [95]. In addition, the detection window varies depending on the analytical method and the biological matrix (Table 3, Figure 3). In these studies, both inter and intra-subject differences were observed. The detection window depends on several factors, including the analyte, time of consumption, dosage, metabolism, excretion of the drug, and other physiological factors.

3.2. Oral Fluid as the Preferred Biological Matrix

In recent years, increasing research efforts have focused on using oral fluid specimens as the matrix of choice for cannabinoid detection [36,41,44,73,86,103,104,105,106]. It is relatively easy and fast to collect an oral fluid specimen, and it can be done on-site under direct supervision, eliminating any chances of an adulterated sample. Various analytical methods were developed for the detection of cannabinoids in oral fluid specimens, which are similar to methods for detection in urine; however, because of the differences in the matrix composition, several changes were made over the years in order to improve their accuracy. Moreover, oral fluid specimens are the preferred choice in order to detect recent cannabis intake. In this case, the analyte of interest is the parent drug, THC. Due to the direct contamination of the oral cavity with THC during smoking, significantly high values of the analyte can be found in the first hour after consumption [107]. In addition, it is important to note that cannabinoids bind to proteins to a high degree [35]. For example, unbound THC molecules are absorbed directly into adipose tissues or organs from the blood. Then, through diffusion, THC–protein complexes can pass from the blood into the oral fluid. The pH differences between the blood and the oral fluid keep the THC–protein complexes in the salivary glands. In order for the THC–protein complexes to reach the oral fluid, they need to transfer through five identified barriers, including the capillary wall of the blood vessels, the interstitial space between the capillary wall and the cell membrane of acinar cells, the membrane of the acinar cell, the fluid inside the acinar cell, and the luminal cell membrane [108]. Previous studies investigated the correlations between the cannabinoid concentrations in oral fluid and those in the blood/plasma. Xu C. et al. [44] examined 4080 subjects between 2007 and 2010, and the samples were analyzed using UPLC-MS and HPLC-MS. A correlation was reported between the two matrices in a proportion of up to 90%. Then, in 2014, Gjerde H. et al. [109] compared the two matrices and reported a correlation between them. However, high intra- and inter-subject variability was reported, especially in the first hour after the smoking of cannabis because of the direct contamination of the buccal cavity. The main parameter that influences the correlation between the two matrices is the oral administration of cannabis, which is not yet common worldwide, except for a few countries that have legalized food products that contain cannabis, such as brownies or space cakes [110]. It is not yet fully understood whether the cannabinoid concentrations in the blood can be predicted from the analysis of oral fluid specimens.

3.3. Collection of Oral Fluid Specimens for Cannabinoids Recovery

Properly collecting the oral fluid sample is the first step toward a successful detection analysis. This step involves the collection of the saliva in a special container, usually made from plastic. There are three main methods by which an oral fluid specimen can be collected: passive drool, expectoration, and collection via a collection device (Table 4). The most common method with the best results is the collection via a collection device. This method is officially approved and offers improved sample stability due to the addition of buffers. In general, buffers contain antioxidants to counteract free radicals that can degrade the cannabinoids and pH stabilization compounds such as phosphate [111]. Another aspect to consider is that buffers reduce oral fluid viscosity, improving measurement accuracy and diluting analyte concentrations [66]. Most of the collection devices are made up of a container, pad, buffer, and volume adequacy indicator that changes its color once the specified volume of oral fluid is collected. The sample collection is fast, usually taking around 1–2 min. The pad also acts as a filter for the oral fluid, allowing only liquid absorption. Newer devices demonstrate more homogeneity (Table 5). An important aspect to be considered is the amount of analyte that is recovered from the collection device. When diluting the analyte with buffer, the sample’s stability is increased, and there is a lower loss of analyte. However, the dilution factor has to be taken into consideration, and the analytical method of choice should allow increased sensitivity. In addition, THC is easily absorbed into plastic and requires the use of a solvent to remove it completely. However, some collection devices do not use a buffer and realize poor analyte recovery.

3.4. Stability of Cannabinoids within Oral Fluid Specimens

Generally, the integrity of oral fluid specimens is better than that of urine samples [92]. However, oral fluid specimens are still influenced by multiple parameters. The effects of tobacco, different foods, orange juice, coffee, soymilk, chewing gum, mouthwash, toothpaste, vinegar, and two commercial products specifically made for adulterating the oral fluid matrix were investigated for potential interference [129]. Only vinegar produced one false-positive result from all the tested parameters [41]. In addition, it was previously reported that bicarbonates excreted from salivary glands into the oral fluid offer good buffer properties for containing the cannabinoids [104]. The only problem could be this collection methodology does not use surfactants, thus allowing the cannabinoids to bind to the plastic container, which may then result in the poor recovery of the analyte [115]. The stability of cannabinoids within a biological matrix also depends on several factors, such as buffers, containers, temperature, and exposure to light [35]. Lee D. et al. [130] investigated the stability of cannabinoids within an authentic oral fluid. It was reported that the expectorated oral fluid degraded quickly at room temperature and that the percentage of THC was reduced by half after 10 days. The maximum storage time was found to be 24 weeks for THC fortified in the Quantisal buffer at −20 °C. However, when buffers were used, the recovery of cannabinoids after 28 days ranged from 78 to 118%, depending on the oral fluid collection device [36]. The ability to reuse the same sample for multiple analyses would allow the detection in multiple places or with multiple techniques. Even though the samples can be collected one after another, there were cases when the results were different, or the sample volume was insufficient. The detection process starts with collecting one sample that is then analyzed. Based on the results, when a positive result is obtained, another sample is only then collected and sent to the lab for confirmation. However, the process can become complex and time-consuming when several samples are required. For this purpose, one collection device was developed for collecting two clean oral fluid samples simultaneously, in a two-split tube [131]. Except for the cases of spectrophotometric detections, none of the currently used devices can reuse the sample for multiple analyses. The analytical methods are different and require a specific sample volume for the detection analysis.

4. Detection of Cannabinoids in Oral Fluid Specimens in Lab-Based Techniques and on-Site Point-of-Care Biosensors

The detection of cannabinoids in lab-based techniques is more accurate and sensitive but significantly slower than that in on-site point-of-care biosensors. In addition, on-site point-of-care biosensors usually allow the detection of a single cannabinoid, while the lab-based techniques provide detection results for multiple cannabinoids and their metabolites in parallel. While it may seem preferable to send a sample for cannabinoid detection to a centered lab, in certain circumstances, there is a need for an on-site result. In order to correctly calculate the concentration of the cannabinoids in oral fluid specimens, an accurate volume of approximately 1 mL of an oral fluid specimen is usually collected. Then, after taking into account the additional known buffer volume, the exact concentration can be calibrated for each on-site point-of-care biosensor system [132]. For example, in the case of the StatSure device, the following formula is used:
C c o r r e c t e d = C u n c o r r e c t e d ( 1 + w w _ )   2 ( w w _ )
The variables within the formula include w _ = average weight of empty StatSure device; w = weight of sample and StatSure device; Cuncorrected = uncorrected concentration of analyte; Ccorrected = concentration of analyte corrected for volume of oral fluid collected. Then, the density of the mixture of the oral fluid specimen and the buffer is assumed to be 1 g/mL. Additional measurable parameters are determined, including sensitivity, specificity, accuracy, prevalence, and predictive values (positive or negative). Most biosensor systems for cannabinoid detection show a positive result only above a certain predetermined cutoff value. Another important concern in cannabinoid detection is cross-reactivity. For example, anti-THC antibodies also react with different concentrations of THC-COOH, CBD, and CBN [49]. The detection of cannabinoids in both lab-based techniques (Table 6) and on-site point-of-care biosensors (Table 7) is presented, with the description of the technique as well as the levels of the cannabinoids.

5. Conclusions

This review presents the recent findings regarding the use of oral fluid specimens as the preferred biological matrix for cannabinoid detection in a point-of-care biosensor diagnostic device. Currently, cannabinoids are detected in various biological matrices, including blood, oral fluid, urine, sweat, breath, and hair. The detection window varies depending on the analytical method and the biological matrix used. It is also dependent on several factors, including the analyte, time of consumption, dosage, metabolism, excretion of the drug, and other physiological factors. The detection of cannabinoids in oral fluid and blood specimens provides information on the most recent drug intake, with a detection window between 15 min and up to 24 h in single-use cases. The other most well-studied and used biological matrix, urine, provides information only on the history of use, with a detection window of 14–90 days. Oral fluid is the preferred biological matrix to be used for detection in point-of-care biosensors since blood is a much more complex specimen that requires pretreatment and specialized analytical devices. Moreover, individuals are still entitled to refuse to provide blood samples, as compared to oral fluid specimens, which makes the screening of drug use more difficult to implement. In addition, various conventional techniques and point-of-care biosensors were also reviewed in this study. The details discussed highlight their detection sensitivity and ability for on-site drug use screening in oral fluid specimens. Detection of synthetic cannabinoids in oral fluid is still challenging due to the high number of new compounds that do not work with current technology. Additionally, these synthetic cannabinoids are sometimes mixed with cannabimimetic compounds, which are an entirely new class of substances that need to be detected. Regardless of the challenges, efforts are being made to detect and control such substances by creating POCT devices utilizing cross-reactivity for a class of compounds or better collection devices for the ability to take samples to a full-scale laboratory. With improvements to the current technologies for on-site detection of psychoactive compounds, the accuracy can be improved, and a correlation between the physiological concentration of cannabinoids and levels of impairment is still needed. A joint venture between Biosensorix in Singapore and Eclipsedx in the USA are developing cannabinox, a device able to detect cannabis bioactive compounds, including in saliva [164]. To conclude, this review presents the current pressing technological challenges and highlights the gaps where new technological solutions can be implemented.

Author Contributions

R.S.M.: Conceptualization, Methodology, Resources, Writing—review and editing, Supervision, Project administration, Funding acquisition. E.E.: Conceptualization, Methodology, Writing—review and editing. C.T.: Investigation, Writing—original draft. D.H.: Investigation, Writing—original draft. Y.P.: Conceptualization, Methodology, Writing—review and editing. C.P. Conceptualization, Methodology, Writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

References

  1. Hanson, K.; Garcia, A. State medical marijuana laws. In Proceedings of the National Conference of State Legislators, Denver, CO, USA, 5–8 August 2019. [Google Scholar]
  2. Bifulco, M.; Pisanti, S. Medicinal Use of Cannabis in Europe; EMBO Reports; EMBO: Heidelberg, Germany, 2015; pp. 130–132. [Google Scholar]
  3. Available online: https://www.usnews.com/news/best-states/articles/where-is-marijuana-legal-a-guide-to-marijuana-legalization (accessed on 14 December 2023).
  4. Kokona, A.; Tarricone, I.; Di Forti, M.; Carra, E. Cannabis, Migration, and Psychosis Onset. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 79–88. [Google Scholar]
  5. Linares, I.; Crippa, J.; Chagas, M. Beneficial effects of cannabis and related compounds on sleep. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 877–882. [Google Scholar]
  6. Petrilli, K.; Hines, L.; Adams, S.; Morgan, C.J.; Curran, H.V.; Freeman, T.P. High potency cannabis use, mental health symptoms and cannabis dependence: Triangulating the evidence. Addict. Behav. 2023, 144, 107740. [Google Scholar] [CrossRef] [PubMed]
  7. Hill, M.; Reed, K. Marijuana and Breastfeeding. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 527–532. [Google Scholar]
  8. Norberg, M.M.; Rooke, S.E.; Albertella, L.; Copeland, J.; Kavanagh, D.J.; Lau, A. The first mHealth app for managing cannabis use: Gauging its potential helpfulness. J. Addict. Behav. Ther. Rehabil. 2014, 3, 1. [Google Scholar]
  9. Huestis, M.A.; Smith, M.L. Cannabinoid Markers in Biological Fluids and Tissues: Revealing Intake. Trends Mol. Med. 2018, 24, 156–172. [Google Scholar] [CrossRef] [PubMed]
  10. Johnson, O.E.; Miskelly, G.M.; Rindelaub, J.D. Testing for cannabis intoxication: Current issues and latest advancements. Wiley Interdiscip. Rev. Forensic Sci. 2022, 4, e1450. [Google Scholar] [CrossRef]
  11. Morales, P.; Hurst, D.P.; Reggio, P.H. Molecular targets of the phytocannabinoids: A complex picture. In Phytocannabinoids; Springer: Berlin/Heidelberg, Germany, 2017; pp. 103–131. [Google Scholar]
  12. Radwan, M.M.; Wanas, A.S.; Chandra, S.; ElSohly, M.A. Natural cannabinoids of cannabis and methods of analysis. In Cannabis sativa L.—Botany and Biotechnology; Springer: Berlin/Heidelberg, Germany, 2017; pp. 161–182. [Google Scholar]
  13. Razdan, R.K. Structure-activity relationships in cannabinoids. Pharmacol. Rev. 1986, 38, 75. [Google Scholar] [PubMed]
  14. Pertwee, R.G. The central neuropharmcology of psychotropic cannabinoids. Pharmacol. Ther. 1988, 36, 189–261. [Google Scholar] [CrossRef] [PubMed]
  15. Pertwee, R.G. Pharmacological and therapeutic targets for Δ9 tetrahydrocannabinol and cannabidiol. Euphytica 2004, 140, 73–82. [Google Scholar] [CrossRef]
  16. Grotenhermen, F.; Russo, E.; Zuardi, A.W. Even high doses of oral cannabidiol do not cause THC-like effects in humans: Comment on Merrick et al. Cannabis Cannabinoid Res. 2016, 1, 102–112, Erratum in Cannabis Cannabinoid Res. 2017, 2, 1–4. [Google Scholar] [CrossRef]
  17. Borges, R.; da Silva, A. Cannabidiol as an antioxidant. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. e122–e130. [Google Scholar]
  18. Zuardi, A.; de Souza Crippa, J.; Hallak, J.; Campos, A.; Guimarães, F. The anxiolytic effects of Cannabidiol (CBD). In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. e131–e139. [Google Scholar]
  19. Coimbra, N.; Mendes-Gomes, J.; Da Silva, J.; Dos Anjos-Garcia, T.; Ullah, F.; Almada, R. New Ethological and Morphological Perspectives for the Investigation of Panicolytic-like Effects of Cannabidiol. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. e140–e149. [Google Scholar]
  20. Zalman, D.; Bar-Sela, G. Cannabis and Synthetic Cannabinoids for Cancer Patients: Multiple Palliative Indications Together With Promising Laboratory Antineoplastic Effects. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 859–868. [Google Scholar]
  21. Tellioğlu, T.; Tellioğlu, Z. The use of medical marijuana in the treatment of psychiatric disorders. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 869–876. [Google Scholar]
  22. Kanaan, A.S.; Müller-Vahl, K. Cannabinoid-based medicines for the treatment of gilles de la tourette syndrome. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 883–892. [Google Scholar]
  23. Mecha, M.; Feliú, A.; Carrillo-Salinas, F.; Guaza, C. Cannabidiol and Multiple Sclerosis. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 893–904. [Google Scholar]
  24. Selvarajah, D.; Gandhi, R.; Tesfaye, S. Cannabinoids and Their Effects on Painful Neuropathy. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 905–916. [Google Scholar]
  25. Abdel-Salam, O. Cannabis for Basal Ganglia Disorders (Parkinson Disease and Huntington Disease). In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 917–930. [Google Scholar]
  26. Lahat, A. Medical cannabis for the treatment of inflammatory bowel disease. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 931–938. [Google Scholar]
  27. dos Santos, R.; Hallak, J.; Zuardi, A.; de Souza Crippa, J. Cannabidiol for the treatment of drug use disorders. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 939–946. [Google Scholar]
  28. Vera, G.; Fichna, J.; Abalo, R. Cannabinoids and effects on the gastrointestinal tract: A focus on motility. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 947–957. [Google Scholar]
  29. Deiana, S. Potential Medical Uses of Cannabigerol: A Brief Overview. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. 958–967. [Google Scholar]
  30. Farré, M.; Farré, A.; Fiz, J.; Torrens, M. Cannabis Use in fibromyalgia. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, 2017; pp. e158–e167. [Google Scholar]
  31. Robson, P. Therapeutic potential of cannabinoid medicines. Drug Test. Anal. 2014, 6, 24–30. [Google Scholar] [CrossRef]
  32. Piomelli, D.; Beltramo, M.; Giuffrida, A.; Stella, N. Endogenous Cannabinoid Signaling. Neurobiol. Dis. 1998, 5, 462–473. [Google Scholar] [CrossRef]
  33. Lu, H.-C.; Mackie, K. An Introduction to the Endogenous Cannabinoid System. Biol. Psychiatry 2016, 79, 516–525. [Google Scholar] [CrossRef]
  34. Fonseca, B.M.; Costa, M.A.; Almada, M.; Correia-da-Silva, G.; Teixeira, N.A. Endogenous cannabinoids revisited: A biochemistry perspective. Prostaglandins Other Lipid Mediat. 2013, 102–103, 13–30. [Google Scholar] [CrossRef] [PubMed]
  35. Garrett, E.R.; Hunt, C.A. Physicochemical properties, solubility, and protein binding of Δ9 -tetrahydrocannabinol. J. Pharm. Sci. 1974, 63, 1056–1064. [Google Scholar] [CrossRef] [PubMed]
  36. Lee, D.; Huestis, M.A. Current knowledge on cannabinoids in oral fluid. Drug Test. Anal. 2014, 6, 88–111. [Google Scholar] [CrossRef] [PubMed]
  37. Cowan, D.; Osselton, D.; Robinson, S. Chapter 10—Drug Testing. In Drugs and the Future; Nutt, D., Robbins, T.W., Stimson, G.V., Ince, M., Jackson, A., Eds.; Academic Press: Burlington, ON, Canada, 2007; pp. 315–336. [Google Scholar]
  38. Huestis, M.A. Human cannabinoid pharmacokinetics. Chem. Biodivers. 2007, 4, 1770–1804. [Google Scholar] [CrossRef]
  39. Melanson, S.E.F. Drug-of-Abuse Testing at the Point of Care. Clin. Lab. Med. 2009, 29, 503–509. [Google Scholar] [CrossRef]
  40. Scherer, J.N.; Fiorentin, T.R.; Borille, B.T.; Pasa, G.; Sousa, T.R.V.; von Diemen, L.; Limberger, R.P.; Pechansky, F. Reliability of point-of-collection testing devices for drugs of abuse in oral fluid: A systematic review and meta-analysis. J. Pharm. Biomed. Anal. 2017, 143, 77–85. [Google Scholar] [CrossRef]
  41. Desrosiers, N.A.; Huestis, M.A. Oral Fluid Drug Testing: Analytical Approaches, Issues and Interpretation of Results. J. Anal. Toxicol. 2019, 43, 415–443. [Google Scholar] [CrossRef]
  42. Mazina, J.; Spiljova, A.; Vaher, M.; Kaljurand, M.; Kulp, M. A rapid capillary electrophoresis method with LED-induced native fluorescence detection for the analysis of cannabinoids in oral fluid. J. Anal. Methods 2015, 7, 7741–7747. [Google Scholar] [CrossRef]
  43. Stevenson, H.; Bacon, A.; Joseph, K.M.; Gwandaru, W.R.W.; Bhide, A.; Sankhala, D.; Dhamu, V.N.; Prasad, S. A rapid response electrochemical biosensor for detecting THC in saliva. Sci. Rep. 2019, 9, 12701. [Google Scholar] [CrossRef]
  44. Xu, C.; Wang, W.; Wang, S.; Hou, K.; Li, H. Potential analytical methods for on-site oral drug test: Recent developments and applications. Trends Anal. Chem. 2019, 120, 115649. [Google Scholar] [CrossRef]
  45. Dinis-Oliveira, R.J. Heterogeneous and homogeneous immunoassays for drug analysis. Bioanalysis 2014, 6, 2877–2896. [Google Scholar] [CrossRef] [PubMed]
  46. Drummer, O.H. Drug testing in oral fluid. Clin. Biochem. Rev. 2006, 27, 147–159. [Google Scholar] [PubMed]
  47. Yu, H.; Lee, H.; Cheong, J.; Woo, S.W.; Oh, J.; Oh, H.-K.; Lee, J.-H.; Zheng, H.; Castro, C.M.; Yoo, Y.-E.; et al. A rapid assay provides on-site quantification of tetrahydrocannabinol in oral fluid. Sci. Transl. Med. 2021, 13, eabe2352. [Google Scholar] [CrossRef]
  48. Wang, K.; Qin, W.; Hou, Y.; Xiao, K.; Yan, W. The application of lateral flow immunoassay in point of care testing: A review. Nano Biomed. Eng. 2016, 8, 172–183. [Google Scholar] [CrossRef]
  49. Schwope, D.M.; Milman, G.; Huestis, M.A. Validation of an enzyme immunoassay for detection and semiquantification of cannabinoids in oral fluid. Clin. Chem. 2010, 56, 1007–1014. [Google Scholar] [CrossRef] [PubMed]
  50. Datta, P. Immunoassay Design for Screening of Drugs of Abuse. In Critical Issues in Alcohol and Drugs of Abuse Testing; Elsevier: Amsterdam, The Netherlands, 2019; pp. 121–128. [Google Scholar]
  51. Vanstechelman, S.; Isalberti, C.; Van der Linden, T.; Pil, K.; Legrand, S.-A.; Verstraete, A.G. Analytical evaluation of four on-site oral fluid drug testing devices. J. Anal. Toxicol. 2012, 36, 136–140. [Google Scholar] [CrossRef]
  52. Carrio, A.; Sampedro, C.; Sanchez-Lopez, J.L.; Pimienta, M.; Campoy, P. Automated Low-Cost Smartphone-Based Lateral Flow Saliva Test Reader for Drugs-of-Abuse Detection. Sensors 2015, 15, 29569–29593. [Google Scholar] [CrossRef]
  53. Niedbala, R.S.; Feindt, H.; Kardos, K.; Vail, T.; Burton, J.; Bielska, B.; Li, S.; Milunic, D.; Bourdelle, P.; Vallejo, R. Detection of analytes by immunoassay using up-converting phosphor technology. Anal. Biochem. 2001, 293, 22–30. [Google Scholar] [CrossRef]
  54. Corstjens, P.L.A.M.; Li, S.; Zuiderwijk, M.; Kardos, K.; Abrams, W.R.; Niedbala, R.S.; Tanke, H.J. Infrared up-converting phosphors for bioassays. IEEE Proc. Nanobiotechnol. 2005, 152, 64–72. [Google Scholar] [CrossRef]
  55. Swortwood, M.J.; Newmeyer, M.N.; Abulseoud, O.A.; Andersson, M.; Barnes, A.J.; Scheidweiler, K.B.; Huestis, M.A. On-site oral fluid Δ 9-tetrahydrocannabinol (THC) screening after controlled smoked, vaporized, and oral cannabis administration. Forensic Toxicol. 2017, 35, 133–145. [Google Scholar] [CrossRef]
  56. Crouch, D.J. Oral fluid collection: The neglected variable in oral fluid testing. Forensic Sci. Int. 2005, 150, 165–173. [Google Scholar] [CrossRef] [PubMed]
  57. Dickson, S.; Park, A.; Nolan, S.; Kenworthy, S.; Nicholson, C.; Midgley, J.; Pinfold, R.; Hampton, S. The recovery of illicit drugs from oral fluid sampling devices. Forensic Sci. Int. 2007, 165, 78–84. [Google Scholar] [CrossRef] [PubMed]
  58. Amini, K.; Sepehrifard, A.; Valinasabpouri, A.; Safruk, J.; Angelone, D.; de Campos Lourenco, T. Recent advances in electrochemical sensor technologies for THC detection—A narrative review. J. Cannabis Res. 2022, 4, 12. [Google Scholar] [CrossRef] [PubMed]
  59. Klimuntowski, M.; Alam, M.M.; Singh, G.; Howlader, M.M.R. Electrochemical Sensing of Cannabinoids in Biofluids: A Noninvasive Tool for Drug Detection. ACS Sens. 2020, 5, 620–636. [Google Scholar] [CrossRef] [PubMed]
  60. Han, K.; Liu, T.; Wang, Y.; Miao, P. Electrochemical aptasensors for detection of small molecules, macromolecules, and cells. Rev. Anal. Chem. 2016, 35, 201–211. [Google Scholar] [CrossRef]
  61. Laghlimi, C.; Moutcine, A.; Chtaini, A.; Isaad, J.; Soufi, A.; Ziat, Y.; Amhamdi, H.; Belkhanchi, H. Recent advances in electrochemical sensors and biosensors for monitoring drugs and metabolites in pharmaceutical and biological samples. Admet Dmpk 2023, 11, 151–173. [Google Scholar] [CrossRef]
  62. Pholsiri, T.; Khamcharoen, W.; Vimolmangkang, S.; Siangproh, W.; Chailapakul, O. Paper-based electrochemical sensor for simultaneous detection of salivary Δ9-tetrahydrocannabinol and thiocyanate to differentiate illegal cannabis smokers. Sens. Actuators B Chem. 2023, 383, 133571. [Google Scholar] [CrossRef]
  63. Joosten, F.; Parrilla, M.; van Nuijs, A.L.N.; Ozoemena, K.I.; De Wael, K. Electrochemical detection of illicit drugs in oral fluid: Potential for forensic drug testing. Electrochim. Acta 2022, 436, 141309. [Google Scholar] [CrossRef]
  64. Moore, C.; Coulter, C.; Rana, S.; Vincent, M.; Snares, J. Analytical Procedure for the Determination of the Marijuana Metabolite 11-nor-Δ9-Tetrahydrocannabinol-9-carboxylic Acid in Oral Fluid Specimens. J. Anal. Toxicol. 2006, 30, 409–412. [Google Scholar] [CrossRef]
  65. Verstraete, A.G. Detection times of drugs of abuse in blood, urine, and oral fluid. Ther. Drug Monit. 2004, 26, 200–205. [Google Scholar] [CrossRef] [PubMed]
  66. Bosker, W.M.; Huestis, M.A. Oral Fluid Testing for Drugs of Abuse. Clin. Chem. 2009, 55, 1910–1931. [Google Scholar] [CrossRef] [PubMed]
  67. Ramaekers, J.G.; Moeller, M.; van Ruitenbeek, P.; Theunissen, E.L.; Schneider, E.; Kauert, G. Cognition and motor control as a function of Δ9-THC concentration in serum and oral fluid: Limits of impairment. Drug Alcohol Depend. 2006, 85, 114–122. [Google Scholar] [CrossRef] [PubMed]
  68. Ginsburg, B.; Abuse, A. Strengths and limitations of two cannabis-impaired driving detection methods: A review of the literature. Am. J. Drug Alcohol Abus. 2019, 45, 610–622. [Google Scholar] [CrossRef] [PubMed]
  69. Agius, R.; Nadulski, T.; Moore, C. Validation of LUCIO®-Direct-ELISA kits for the detection of drugs of abuse in urine: Application to the new German driving licence re-granting guidelines. Forensic Sci. Int. 2012, 215, 38–45. [Google Scholar] [CrossRef] [PubMed]
  70. Aizpurua-Olaizola, O.; Zarandona, I.; Ortiz, L.; Navarro, P.; Etxebarria, N.; Usobiaga, A. Simultaneous quantification of major cannabinoids and metabolites in human urine and plasma by HPLC-MS/MS and enzyme-alkaline hydrolysis. Drug Test. Anal. 2017, 9, 626–633. [Google Scholar] [CrossRef] [PubMed]
  71. Desrosiers, N.A.; Lee, D.; Concheiro-Guisan, M.; Scheidweiler, K.B.; Gorelick, D.A.; Huestis, M.A. Urinary cannabinoid disposition in occasional and frequent smokers: Is THC-glucuronide in sequential urine samples a marker of recent use in frequent smokers? Clin. Chem. 2014, 60, 361–372. [Google Scholar] [CrossRef] [PubMed]
  72. Guidet, C.; Gregoire, M.; Le Dreau, A.; Vrignaud, B.; Deslandes, G.; Monteil-Ganière, C. Cannabis intoxication after accidental ingestion in infants: Urine and plasma concentrations of Δ-9-tetrahydrocannabinol (THC), THC-COOH and 11-OH-THC in 10 patients. Clin. Toxicol. 2019, 58, 421–423. [Google Scholar] [CrossRef]
  73. Hayley, A.C.; Downey, L.A.; Hansen, G.; Dowell, A.; Savins, D.; Buchta, R.; Catubig, R.; Houlden, R.; Stough, C. Detection of delta-9-tetrahydrocannabinol (THC) in oral fluid, blood and urine following oral consumption of low-content THC hemp oil. Forensic Sci. Int. 2018, 284, 101–106. [Google Scholar] [CrossRef]
  74. Heltsley, R.; DePriest, A.; Black, D.L.; Crouch, D.J.; Robert, T.; Marshall, L.; Meadors, V.M.; Caplan, Y.H.; Cone, E.J. Oral fluid drug testing of chronic pain patients. II. Comparison of paired oral fluid and urine specimens. J. Anal. Toxicol. 2012, 36, 75–80. [Google Scholar] [CrossRef]
  75. Khidr, H.I.; Tegin, C. Strategies for preventing and detecting false-negatives in urine drug screens. Curr. Psychiatry 2017, 16, e1–e3. [Google Scholar]
  76. Kim, J.Y.; Kwon, W.; Kim, H.S.; Suh, S.I.; In, M.K. Estimation of measurement uncertainty for the quantification of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid and its glucuronide in urine using liquid chromatography-tandem mass spectrometry. J. Anal. Toxicol. 2014, 38, 164–170. [Google Scholar] [CrossRef] [PubMed]
  77. Kwon, W.; Kim, J.Y.; Suh, S.; In, M.K. Direct quantification of 11-nor-Δ9-tetrahydrocannabinol-9- carboxylic acid and its glucuronide in urine using liquid chromatography-tandem mass spectrometry. Anal. Methods 2013, 5, 3028–3034. [Google Scholar] [CrossRef]
  78. Lillsunde, P.; Korte, T. Comprehensive drug screening in urine using solid-phase extraction and combined TLC and GC/MS identification. J. Anal. Toxicol. 1991, 15, 71–81. [Google Scholar] [CrossRef] [PubMed]
  79. Lin, C.N.; Nelson, G.J.; McMillin, G.A. Evaluation of the nexscreen and drugcheck waive RT urine drug detection cups. J. Anal. Toxicol. 2013, 37, 30–36. [Google Scholar] [CrossRef] [PubMed]
  80. Maharjan, A.S.; Johnson-Davis, K.L. Issues of Interferences With Immunoassays Used for Screening of Drugs of Abuse in Urine, 2nd ed.; Elsevier Inc.: Amsterdam, The Netherlands, 2019; pp. 129–139. [Google Scholar]
  81. Manno, B.R.; Manno, B.S.; Kemp, P.M.; Alford, D.D.; Abukhalaf, I.K.; McWilliams, M.E.; Hagaman, B.S.; Fitzgerald, B.S. Temporal indication of marijuana use can be estimated from plasma and urine concentrations of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid. J. Anal. Toxicol. 2001, 25, 538–549. [Google Scholar] [CrossRef]
  82. Meier, U.; Dussy, F.; Scheurer, E.; Mercer-Chalmers-Bender, K.; Hangartner, S. Cannabinoid concentrations in blood and urine after smoking cannabidiol joints. Forensic Sci. Int. 2018, 291, 62–67. [Google Scholar] [CrossRef]
  83. Mordal, J.; Holm, B.; Mørland, J.; Bramness, J.G. Recent substance intake among patients admitted to acute psychiatric wards: Physician’s assessment and on-site urine testing compared with comprehensive laboratory analyses. J. Clin. Psychopharmacol. 2010, 30, 455–459. [Google Scholar] [CrossRef]
  84. Niedbala, R.S.; Kardos, K.W.; Fritch, D.F.; Kardos, S.; Fries, T.; Waga, J.; Robb, J.; Cone, E.J. Detection of marijuana use by oral fluid and urine analysis following single-dose administration of smoked and oral marijuana. J. Anal. Toxicol. 2001, 25, 289–303. [Google Scholar] [CrossRef]
  85. Pacifici, R.; Pichini, S.; Pellegrini, M.; Rotolo, M.C.; Giorgetti, R.; Tagliabracci, A.; Busardò, F.P.; Huestis, M.A. THC and CBD concentrations in blood, oral fluid and urine following a single and repeated administration of “light cannabis”. Anal. Clin. Chem. 2020, 58, 682–689. [Google Scholar] [CrossRef]
  86. Pacifici, R.; Pichini, S.; Pellegrini, M.; Tittarelli, R.; Pantano, F.; Mannocchi, G.; Rotolo, M.C.; Busardò, F.P. Determination of cannabinoids in oral fluid and urine of “light cannabis” consumers: A pilot study. Clin. Chem. Lab. Med. 2019, 57, 238–243. [Google Scholar] [CrossRef] [PubMed]
  87. Raes, E.; Verstraete, A.G. Usefulness of roadside urine drug screening in drivers suspected of driving under the influence of drugs (DUID). J. Anal. Toxicol. 2005, 29, 632–636. [Google Scholar] [CrossRef] [PubMed]
  88. Röhrich, J.; Schimmel, I.; Zörntlein, S.; Becker, J.; Drobnik, S.; Kaufmann, T.; Kuntz, V.; Urban, R. Concentrations of Δ9-tetrahydrocannabinol and 11-nor-9-carboxytetrahydrocannabinol in blood and urine after passive exposure to cannabis smoke in a coffee shop. J. Anal. Toxicol. 2010, 34, 196–203. [Google Scholar] [CrossRef] [PubMed]
  89. Teixeira, H.; Verstraete, A.; Proença, P.; Corte-Real, F.; Monsanto, P.; Vieira, D.N. Validated method for the simultaneous determination of Δ9-THC and Δ9-THC-COOH in oral fluid, urine and whole blood using solid-phase extraction and liquid chromatography-mass spectrometry with electrospray ionization. Forensic Sci. Int. 2007, 170, 148–155. [Google Scholar] [CrossRef] [PubMed]
  90. Toennes, S.W.; Kauert, G.F.; Steinmeyer, S.; Moeller, M.R. Driving under the influence of drugs—Evaluation of analytical data of drugs in oral fluid, serum and urine, and correlation with impairment symptoms. Forensic Sci. Int. 2005, 152, 149–155. [Google Scholar] [CrossRef] [PubMed]
  91. Woelfel, J.A. Drug abuse urine tests: False-positive results. Pharm. Lett. Prescr. Lett. 2005, 21, 1–5. [Google Scholar]
  92. Allen, K.R. Screening for drugs of abuse: Which matrix, oral fluid or urine? Ann. Clin. Biochem. 2011, 48, 531–541. [Google Scholar] [CrossRef]
  93. Akhtar, M.T.; Shaari, K.; Verpoorte, R. Biotransformation of Tetrahydrocannabinol. Phytochem. Rev. 2016, 15, 921–934. [Google Scholar] [CrossRef]
  94. Myers, R.E.; Sprague, J.M.; Meikle, H.; Anderson, V.; Symmes, D.; Schneider, G.E. Delta-9-Tetrahydrocannabinol: Metabolism and Disposition. Clin. Pharmacol. Ther. 1971, 272, 1965–1967. [Google Scholar]
  95. Kabir, A.; Locatelli, M.; Ulusoy, H.I. Recent trends in microextraction techniques employed in analytical and bioanalytical sample preparation. Separations 2017, 4, 36. [Google Scholar] [CrossRef]
  96. Wiencek, J.R.; Colby, J.M.; Nichols, J.H. Rapid Assessment of Drugs of Abuse. Adv. Clin. Chem. 2017, 80, 193–225. [Google Scholar] [PubMed]
  97. Anizan, S.; Huestis, M.A. The potential role of oral fluid in antidoping testing. Clin. Chem. 2014, 60, 307–322. [Google Scholar] [CrossRef] [PubMed]
  98. Cone, E.J.; Bigelow, G.E.; Herrmann, E.S.; Mitchell, J.M.; LoDico, C.; Flegel, R.; Vandrey, R. Nonsmoker exposure to secondhand cannabis smoke. III. Oral fluid and blood drug concentrations and corresponding subjective effects. J. Anal. Toxicol. 2015, 39, 497–509. [Google Scholar] [CrossRef] [PubMed]
  99. Lee, D.; Schwope, D.M.; Milman, G.; Barnes, A.J.; Gorelick, D.A.; Huestis, M.A. Cannabinoid disposition in oral fluid after controlled smoked cannabis. Clin. Chem. 2012, 58, 748–756. [Google Scholar] [CrossRef] [PubMed]
  100. Newmeyer, M.N.; Desrosiers, N.A.; Lee, D.; Mendu, D.R.; Barnes, A.J.; Gorelick, D.A.; Huestis, M.A. Cannabinoid disposition in oral fluid after controlled cannabis smoking in frequent and occasional smokers. Drug Test. Anal. 2014, 6, 1002–1010. [Google Scholar] [CrossRef] [PubMed]
  101. Sobolesky, P.M.; Smith, B.E.; Hubbard, J.A.; Stone, J.; Marcotte, T.D.; Grelotti, D.J.; Grant, I.; Fitzgerald, R.L. Validation of a liquid chromatography-tandem mass spectrometry method for analyzing cannabinoids in oral fluid. Clin. Chim. Acta 2019, 491, 30–38. [Google Scholar] [CrossRef] [PubMed]
  102. Desrosiers, N.A.; Lee, D.; Schwope, D.M.; Milman, G.; Barnes, A.J.; Gorelick, D.A.; Huestis, M. On-site test for cannabinoids in oral fluid. Clin. Chem. 2012, 58, 1418–1425. [Google Scholar] [CrossRef]
  103. Dobri, S.C.D.; Moslehi, A.H.; Davies, T.C. Are oral fluid testing devices effective for the roadside detection of recent cannabis use? A systematic review. Public Health 2019, 171, 57–65. [Google Scholar] [CrossRef]
  104. White, R.M.; Moore, C.M. Detection of Drugs and Their Metabolites in Oral Fluid; Elsevier: Amsterdam, The Netherlands, 2018. [Google Scholar]
  105. Saar-Reismaa, P.; Erme, E.; Vaher, M.; Kulp, M.; Kaljurand, M.; Mazina-Šinkar, J. In Situ Determination of Illegal Drugs in Oral Fluid by Portable Capillary Electrophoresis with Deep UV Excited Fluorescence Detection. Anal. Chem. 2018, 90, 6253–6258. [Google Scholar] [CrossRef]
  106. Antunes, M.; Barroso, M.; Gallardo, E. Analysis of Cannabinoids in Biological Specimens: An Update. Int. J. Environ. Res. Public Health 2023, 20, 2312. [Google Scholar] [CrossRef]
  107. Huestis, M.A.; Cone, E. Relationship of Δ9-tetrahydrocannabinol concentrations in oral fluid and plasma after controlled administration of smoked cannabis. J. Anal. Toxicol. 2004, 28, 394–399. [Google Scholar] [CrossRef] [PubMed]
  108. Forde, M.D.; Koka, S.; Eckert, S.E.; Carr, A.B.; Wong, D.T. Systemic assessments utilizing saliva: Part 1—General considerations and current assessments. Int. J. Prosthodont. 2006, 19, 43–52. [Google Scholar] [PubMed]
  109. Gjerde, H.; Langel, K.; Favretto, D.; Verstraete, A.G. Estimation of equivalent cutoff thresholds in blood and oral fluid for drug prevalence studies. J. Anal. Toxicol. 2014, 38, 92–98. [Google Scholar] [CrossRef] [PubMed]
  110. Spindle, T.R.; Cone, E.J.; Herrmann, E.S.; Mitchell, J.M.; Flegel, R.; LoDico, C.; Bigelow, G.E.; Vandrey, R. Pharmacokinetics of Cannabis Brownies: A Controlled Examination of Δ9-Tetrahydrocannabinol and Metabolites in Blood and Oral Fluid of Healthy Adult Males and Females. J. Anal. Toxicol. 2020, 44, 661–671. [Google Scholar] [CrossRef] [PubMed]
  111. Moore, C.; Vincent, M.; Rana, S.; Coulter, C.; Agrawal, A.; Soares, J. Stability of Delta(9)-tetrahydrocannabinol (THC) in oral fluid using the Quantisal collection device. Forensic Sci. Int. 2006, 164, 126–130. [Google Scholar] [CrossRef] [PubMed]
  112. Cohier, C.; Mégarbane, B.; Roussel, O. Illicit Drugs in Oral Fluid: Evaluation of Two Collection Devices. J. Anal. Toxicol. 2017, 41, 71–76. [Google Scholar] [CrossRef] [PubMed]
  113. Wille, S.M.R.; Di Fazio, V.; Ramírez-Fernandez, M.d.M.; Kummer, N.; Samyn, N. Driving Under the Influence of Cannabis: Pitfalls, Validation, and Quality Control of a UPLC-MS/MS Method for the Quantification of Tetrahydrocannabinol in Oral Fluid Collected With StatSure, Quantisal, or Certus Collector. Ther. Drug Monit. 2013, 35, 101–111. [Google Scholar] [CrossRef]
  114. Jaffe, A.; Molnar, S.; Williams, N.; Wong, E.; Todd, T.; Caputo, C.; Tolentino, J.; Ye, S. Review and Recommendations for Drug Testing in Substance Use Treatment Contexts. J. Reward Defic. Syndr. Addict. Sci. 2016, 2, 28–45. [Google Scholar] [CrossRef]
  115. Langel, K.; Engblom, C.; Pehrsson, A.; Gunnar, T.; Ariniemi, K.; Lillsunde, P. Drug Testing in Oral Fluid—Evaluation of Sample Collection Devices. J. Anal. Toxicol. 2008, 32, 393–401. [Google Scholar] [CrossRef]
  116. Ventura, M.; Pichini, S.; Ventura, R.; Leal, S.; Zuccaro, P.; Pacifici, R.; de la Torre, R. Stability of drugs of abuse in oral fluid collection devices with purpose of external quality assessment schemes. Ther. Drug Monit. 2009, 31, 277–280. [Google Scholar] [CrossRef]
  117. Drummer, O.H.; Gerostamoulos, D.; Chu, M.; Swann, P.; Boorman, M.; Cairns, I. Drugs in oral fluid in randomly selected drivers. Forensic Sci. Int. 2007, 170, 105–110. [Google Scholar] [CrossRef] [PubMed]
  118. Speedy, T.; Baldwin, D.; Jowett, G.; Gallina, M.; Jehanli, A. Development and validation of the Cozart® DDS oral fluid collection device. Forensic Sci. Int. 2007, 170, 117–120. [Google Scholar] [CrossRef] [PubMed]
  119. Pechansky, F.; Scherer, J.N.; Schuch, J.B.; Roglio, V.; Telles, Y.M.; Silvestrin, R.; Pasa, G.; Sousa, T. User experience and operational feasibility of four point-of-collection oral fluid drug-testing devices according to Brazilian traffic agents. Traffic Inj. Prev. 2019, 20, 30–36. [Google Scholar] [CrossRef] [PubMed]
  120. Hall, A.-J.; Warner, J.V.; Henman, M.G.; Ferguson, W.E. Recovery of drugs of abuse from Dräger DCD5000 oral fluid collection device in Australia. J. Anal. Toxicol. 2015, 39, 140–143. [Google Scholar] [CrossRef] [PubMed]
  121. Richeval, C.; Dumestre-Toulet, V.; Wiart, J.-F.; Vanhoye, X.; Humbert, L.; Nachon-Phanithavong, M.; Allorge, D.; Gaulier, J.-m. New psychoactive substances in oral fluid of drivers around a music festival in south-west France in 2017. Forensic Sci. Int. 2019, 297, 265–269. [Google Scholar] [CrossRef] [PubMed]
  122. Engblom, C.; Gunnar, T.; Rantanen, A.; Lillsunde, P. Driving Under the Influence of Drugs-Amphetamine Concentrations in Oral Fluid and Whole Blood Samples. J. Anal. Toxicol. 2007, 31, 276–280. [Google Scholar] [CrossRef] [PubMed]
  123. Desrosiers, N.A.; Scheidweiler, K.B.; Huestis, M.A. Quantification of six cannabinoids and metabolites in oral fluid by liquid chromatography-tandem mass spectrometry. Drug Test. Anal. 2015, 7, 684–694. [Google Scholar] [CrossRef]
  124. Kauert, G.F.; Iwersen-Bergmann, S.; Toennes, S.W. Assay of Δ9-Tetrahydrocannabinol (THC) in Oral Fluid—Evaluation of the OraSure Oral Specimen Collection Device. J. Anal. Toxicol. 2006, 30, 274–277. [Google Scholar] [CrossRef]
  125. Quintela, O.; Crouch, D.J.; Andrenyak, D. Recovery of drugs of abuse from the Immunalysis Quantisal™ oral fluid collection device. J. Anal. Toxicol. 2006, 30, 614–616. [Google Scholar] [CrossRef]
  126. Beckham, J.C.; Adkisson, K.A.; Hertzberg, J.; Kimbrel, N.A.; Budney, A.J.; Stephens, R.S.; Moore, S.D.; Calhoun, P.S. Mobile contingency management as an adjunctive treatment for co-morbid cannabis use disorder and cigarette smoking. Addict. Behav. 2018, 79, 86–92. [Google Scholar] [CrossRef]
  127. Desrosiers, N.A.; Milman, G.; Mendu, D.R.; Lee, D.; Barnes, A.J.; Gorelick, D.A.; Huestis, M.A. Cannabinoids in oral fluid by on-site immunoassay and by GC-MS using two different oral fluid collection devices. Anal. Bioanal. Chem. 2014, 406, 4117–4128. [Google Scholar] [CrossRef] [PubMed]
  128. Saar-Reismaa, P.; Tretjakova, A.; Mazina-Šinkar, J.; Vaher, M.; Kaljurand, M.; Kulp, M. Rapid and sensitive capillary electrophoresis method for the analysis of Ecstasy in an oral fluid. Talanta 2019, 197, 390–396. [Google Scholar] [CrossRef] [PubMed]
  129. Wong, R.C.; Tran, M.; Tung, J.K. Oral fluid drug tests: Effects of adulterants and foodstuffs. Forensic Sci. Int. 2005, 150, 175–180. [Google Scholar] [CrossRef] [PubMed]
  130. Lee, D.; Milman, G.; Schwope, D.M.; Barnes, A.J.; Gorelick, D.A.; Huestis, M.A. Cannabinoid Stability in Authentic Oral Fluid after Controlled Cannabis Smoking. Clin. Chem. 2012, 58, 1101–1109. [Google Scholar] [CrossRef]
  131. UltraSal-2 Oral Fluid Collection Device. In Datasheet; Neogen Corporation: Lansing, MI, USA, 2016; Available online: https://toxicology.neogen.com (accessed on 14 December 2023).
  132. Tom Blencowe, A.P.a.P.L. (Ed.) DRUID—Driving under the Influence of Drugs, Alcohol and Medicines in Analytical Evaluation of Oral Fluid Screening Devices and Preceding Selection Procedures; Technical University of Denmark: Kongens Lyngby, Denmark, 2010. [Google Scholar]
  133. Concheiro, M.; De Castro, A.; Quintela, O.; Cruz, A.; Lopez-Rivadulla, M. Development and validation of a method for the quantitation of Δ9tetrahydrocannabinol in oral fluid by liquid chromatography electrospray–mass-spectrometry. J. Chromatogr. B 2004, 810, 319–324. [Google Scholar] [CrossRef]
  134. Teixeira, H.; Proença, P.; Verstraete, A.; Corte-Real, F.; Vieira, D.N. Analysis of Δ9-tetrahydrocannabinol in oral fluid samples using solid-phase extraction and high-performance liquid chromatography–electrospray ionization mass spectrometry. Forensic Sci. Int. 2005, 150, 205–211. [Google Scholar] [CrossRef]
  135. Laloup, M.; Fernandez, M.d.M.R.; Wood, M.; Boeck, G.D.; Henquet, C.; Maes, V.; Samyn, N. Quantitative analysis of Δ9-tetrahydrocannabinol in preserved oral fluid by liquid chromatography–tandem mass spectrometry. J. Chromatogr. A 2005, 1082, 15–24. [Google Scholar] [CrossRef]
  136. Day, D.; Kuntz, D.J.; Feldman, M.; Presley, L. Detection of THCA in Oral Fluid by GC-MS-MS. J. Anal. Toxicol. 2006, 30, 645–650. [Google Scholar] [CrossRef]
  137. Moore, C.; Rana, S.; Coulter, C. Simultaneous identification of 2-carboxy-tetrahydrocannabinol, tetrahydrocannabinol, cannabinol and cannabidiol in oral fluid. J. Chromatogr. B 2007, 852, 459–464. [Google Scholar] [CrossRef]
  138. Quintela, O.; Andrenyak, D.M.; Hoggan, A.M.; Crouch, D.J. A Validated Method for the Detection of Δ9-Tetrahydrocannabinol and 11-nor-9-Carboxy-Δ9-Tetrahydrocannabinol in Oral Fluid Samples by Liquid Chromatography Coupled with Quadrupole-Time-of-Flight Mass Spectrometry. J. Anal. Toxicol. 2007, 31, 157–164. [Google Scholar] [CrossRef]
  139. Milman, G.; Barnes, A.J.; Lowe, R.H.; Huestis, M.A. Simultaneous quantification of cannabinoids and metabolites in oral fluid by two-dimensional gas chromatography mass spectrometry. J. Chromatogr. A 2010, 1217, 1513–1521. [Google Scholar] [CrossRef] [PubMed]
  140. Bylda, C.; Leinenbach, A.; Thiele, R.; Kobold, U.; Volmer, D.A. Development of an electrospray LC-MS/MS method for quantification of Δ9-tetrahydrocannabinol and its main metabolite in oral fluid. Drug Test. Anal. 2012, 4, 668–674. [Google Scholar] [CrossRef] [PubMed]
  141. Coulter, C.; Garnier, M.; Moore, C. Analysis of Tetrahydrocannabinol and its Metabolite, 11-Nor-Δ9-Tetrahydrocannabinol-9-Carboxylic Acid, in Oral Fluid using Liquid Chromatography with Tandem Mass Spectrometry. J. Anal. Toxicol. 2012, 36, 413–417. [Google Scholar] [CrossRef]
  142. Molnar, A.; Lewis, J.; Doble, P.; Hansen, G.; Prolov, T.; Fu, S. A rapid and sensitive method for the identification of delta-9-tetrahydrocannabinol in oral fluid by liquid chromatography–tandem mass spectrometry. Forensic Sci. Int. 2012, 215, 92–96. [Google Scholar] [CrossRef] [PubMed]
  143. Lee, P.-D.; Chang, Y.-J.; Lin, K.-L.; Chang, Y. Simultaneous determination of Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in oral fluid using isotope dilution liquid chromatography tandem mass spectrometry. Anal. Bioanal. Chem. 2011, 402, 851–859. [Google Scholar] [CrossRef] [PubMed]
  144. Fabritius, M.; Giroud, C. Letter to the editor regarding “Simultaneous determination of ∆9-tetrahydrocannabinol and 11-nor-9-carboxy-∆9-tetrahydrocannabinol in oral fluid using isotope dilution liquid chromatography tandem mass spectrometry”. Anal. Bioanal. Chem. 2013, 405, 435–437. [Google Scholar] [CrossRef] [PubMed]
  145. Marta Concheiro, D.L.; Elena, L.; Marilyn, A. Huestis. Simultaneous quantification of Δ9-tetrahydrocannabinol, 11-nor-9-carboxy-tetrahydrocannabinol, cannabidiol and cannabinol in oral fluid by microflow-liquid chromatography–high resolution mass spectrometry. J. Chromatogr. A 2013, 1297, 123–130. [Google Scholar] [CrossRef] [PubMed]
  146. Scheidweiler, K.B.; Himes, S.K.; Chen, X.; Liu, H.-F.; Huestis, M.A. 11-Nor-9-carboxy-∆ 9-tetrahydrocannabinol quantification in human oral fluid by liquid chromatography–tandem mass spectrometry. Anal. Bioanal. Chem. 2013, 405, 6019–6027. [Google Scholar] [CrossRef]
  147. Sergi, M.; Montesano, C.; Odoardi, S.; Rocca, L.M.; Fabrizi, G.; Compagnone, D.; Curini, R. Micro extraction by packed sorbent coupled to liquid chromatography tandem mass spectrometry for the rapid and sensitive determination of cannabinoids in oral fluids. J. Chromatogr. A 2013, 1301, 139–146. [Google Scholar] [CrossRef]
  148. Fabritius, M.; Staub, C.; Mangin, P.; Giroud, C. Analysis of cannabinoids in oral fluid by liquid chromatography–tandem mass spectrometry. Forensic Toxicol. 2013, 31, 151–163. [Google Scholar] [CrossRef]
  149. Barnes, A.J.; Scheidweiler, K.B.; Huestis, M.A. Quantification of 11-Nor-9-Carboxy-Δ9-tetrahydrocannabinol in human oral fluid by gas chromatography–tandem mass spectrometry. Ther. Drug Monit. 2014, 36, 225–233. [Google Scholar] [CrossRef] [PubMed]
  150. Kintz, P.; Brunet, B.; Muller, J.-F.; Serra, W.; Villain, M.; Cirimele, V.; Mura, P. Evaluation of the Cozart DDSV test for cannabis in oral fluid. Ther. Drug Monit. 2009, 31, 131–134. [Google Scholar] [CrossRef]
  151. Blencowe, T.; Pehrsson, A.; Lillsunde, P.; Vimpari, K.; Houwing, S.; Smink, B.; Mathijssen, R.; Van der Linden, T.; Legrand, S.-A.; Pil, K.; et al. An analytical evaluation of eight on-site oral fluid drug screening devices using laboratory confirmation results from oral fluid. Forensic Sci. Int. 2011, 208, 173–179. [Google Scholar] [CrossRef]
  152. Strano-Rossi, S.; Castrignanò, E.; Anzillotti, L.; Serpelloni, G.; Mollica, R.; Tagliaro, F.; Pascali, J.P.; Di Stefano, D.; Sgalla, R.; Chiarotti, M. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC–MS/MS analysis. Forensic Sci. Int. 2012, 221, 70–76. [Google Scholar] [CrossRef] [PubMed]
  153. Rohrich, J.; Zörntlein, S.; Becker, J.; Urban, R. Detection of Δ9-tetrahydrocannabinol and amphetamine-type stimulants in oral fluid using the Rapid Stat™ point-of-collection drug-testing device. J. Anal. Toxicol. 2010, 34, 155–161. [Google Scholar] [CrossRef] [PubMed]
  154. Wille, S.M.; Ramírez-Fernández, M.d.M.; Samyn, N.; De Boeck, G. Conventional and alternative matrices for driving under the influence of cannabis: Recent progress and remaining challenges. Bioanalysis 2010, 2, 791–806. [Google Scholar] [CrossRef] [PubMed]
  155. Wille, S.M.; Samyn, N.; del Mar Ramírez-Fernández, M.; De Boeck, G. Evaluation of on-site oral fluid screening using Drugwipe-5+®, RapidSTAT® and Drug Test 5000® for the detection of drugs of abuse in drivers. Forensic Sci. Int. 2010, 198, 2–6. [Google Scholar] [CrossRef]
  156. Cirimele, V.; Villain, M.; Mura, P.; Bernard, M.; Kintz, P. Oral fluid testing for cannabis: On-site Oraline® IV sat device versus GC/MS. Forensic Sci. Int. 2006, 161, 180–184. [Google Scholar] [CrossRef]
  157. Concheiro, M.; de Castro, A.; Quintela, O.; Cruz, A.; López-Rivadulla, M. Confirmation by LC–MS of drugs in oral fluid obtained from roadside testing. Forensic Sci. Int. 2007, 170, 156–162. [Google Scholar] [CrossRef]
  158. Pehrsson, A.; Gunnar, T.; Engblom, C.; Seppä, H.; Jama, A.; Lillsunde, P. Roadside oral fluid testing: Comparison of the results of drugwipe 5 and drugwipe benzodiazepines on-site tests with laboratory confirmation results of oral fluid and whole blood. Forensic Sci. Int. 2008, 175, 140–148. [Google Scholar] [CrossRef]
  159. Pehrsson, A.; Blencowe, T.; Vimpari, K.; Langel, K.; Engblom, C.; Lillsunde, P. An evaluation of on-site oral fluid drug screening devices DrugWipe® 5+ and rapid STAT® using oral fluid for confirmation analysis. J. Anal. Toxicol. 2011, 35, 211–218. [Google Scholar] [CrossRef]
  160. Gentili, S.; Solimini, R.; Tittarelli, R.; Mannocchi, G.; Busardò, F.P. A study on the reliability of an on-site oral fluid drug test in a recreational context. J. Anal. Methods Chem. 2016, 2016, 1234581. [Google Scholar] [CrossRef]
  161. Toennes, S.W.; Schneider, K.; Wunder, C.; Kauert, G.F.; Moeller, M.R.; Theunissen, E.L.; Ramaekers, J.G. Influence of ethanol on the pharmacokinetic properties of Δ9-tetrahydrocannabinol in oral fluid. J. Anal. Toxicol. 2013, 37, 152–158. [Google Scholar] [CrossRef]
  162. Laloup, M.; del Mar Ramirez Fernandez, M.; Wood, M.; De Boeck, G.; Maes, V.; Samyn, N. Correlation of Δ9-tetrahydrocannabinol concentrations determined by LC–MS–MS in oral fluid and plasma from impaired drivers and evaluation of the on-site Dräger DrugTest®. Forensic Sci. Int. 2006, 161, 175–179. [Google Scholar] [CrossRef]
  163. Krotulski, A.J.; Mohr, A.L.A.; Friscia, M.; Logan, B.K. Field Detection of Drugs of Abuse in Oral Fluid Using the Alere™ DDS®2 Mobile Test System with Confirmation by Liquid Chromatography Tandem Mass Spectrometry (LC–MS/MS). J. Anal. Toxicol. 2017, 42, 170–176. [Google Scholar] [CrossRef] [PubMed]
  164. Available online: https://www.startengine.com/offering/eclipsedx (accessed on 14 December 2023).
Figure 1. Cannabinoids route inside the human body after consumption.
Figure 1. Cannabinoids route inside the human body after consumption.
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Figure 2. Detection of cannabis from oral fluid specimens.
Figure 2. Detection of cannabis from oral fluid specimens.
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Figure 3. Detection window of cannabinoids in urine, blood, and oral fluid specimens.
Figure 3. Detection window of cannabinoids in urine, blood, and oral fluid specimens.
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Table 1. Conventional analytical techniques for the detection of cannabinoids in biological matrices.
Table 1. Conventional analytical techniques for the detection of cannabinoids in biological matrices.
Analytical TechniqueSensitivityBloodOral FluidUrineSweatBreathHairPoint-of-Care
ImmunoassayHighYesYesYesYesNoYesYes
General spectrophotometry (ultraviolet, infrared, fluorescence, visible)LowNoYesNoNoNoNoYes
RamanModerate NoYesNoYesNoNoYes
Nuclear magnetic resonanceModerateYesNoYesNoNoNoNo
Gas chromatography-mass spectrometryHighYesYesYesYesYesYesNot yet
Liquid chromatography-mass spectrometryHigh YesYesYesYesNoYesNot yet
High-performance liquid chromatography-mass spectrometryHigh YesYesYesYesYesYesNo
Isotope ratio mass spectrometryLow NoNoYesNoNoNoNo
Thin-layer chromatographyLow YesYesYesNoNoNoNo
Gas chromatography–nitrogen phosphorous detectorModerate YesYesYesYesNoNoNo
Gas chromatography–flame ionization detectorLow YesYesYesYesYesNoNo
Liquid chromatography–ultraviolet detectorLow YesNoYesNoNoNoNo
ChemiluminescenceHigh YesYesYesYesYesYesNot yet
Electrochemical detectorHigh YesYesYesYesYesYesYes
Capillary electrophoresisHigh YesYesYesYesNoYesYes
Supercritical fluid chromatographyModerate YesYesYesYesNoNoNo
Detection ability of analytical devices for cannabinoids in various biological matrices, including blood, oral fluid, urine, sweat, breath, and hair. The sensitivity of the devices and whether they are suitable for use on-site as point-of-care devices are also specified. The bold and color highlight the techniques and specific matrix that can be used for POCT devices.
Table 2. Biological matrices for the detection of cannabinoids [37,41].
Table 2. Biological matrices for the detection of cannabinoids [37,41].
Biological MatrixAdvantagesDisadvantageCannabinoids Detection
Blood
  • Indicates recent intake
  • Samples adulteration is eliminated
  • Interpretation of results is easy and accurate
  • Sample collection is difficult and can be done only by trained personnel
  • Short detection times, also dependent on the analyte concentration
  • Analysis is complex, costly, and requires specialized laboratory
  • Current technologies are not developed for point-of-care testing
Show recent drug intake
Urine
  • Relatively easy to collect
  • High concentration of analytes
  • Large sample volumes
  • Provides a history of drug use between 2 days to several weeks
  • Easy and inexpensive to analyze
  • Suitable for workplace and compliance testing
  • No need for sample pretreatment
  • Point-of-care test kits are available
  • Sample is easy to adulterate
  • Interpretation of results can be difficult
  • Mostly contains metabolites and not parent drug; not suitable for detecting a recent intake
  • Observed sample collection is considered a personal privacy violation
It does not show recent drug intake but offers a view of drug usage over the last month
Oral fluid
  • Easy to collect without the intrusion of privacy
  • Can collect several samples
  • Contains parent drug
  • Difficult to adulterate
  • No need for specialized personnel
  • Suitable for the workplace, compliance, and forensic testing
  • Point-of-care-test kits available
  • Indicates recent intake
  • New analytical techniques can be developed
  • High inter- and intra-subject variability
  • Sample size limited
  • Drug concentration may be low and subsequently difficult to analyze
  • Interpretation of results is complex
  • Requires confirmatory analysis with a very sensitive analytical method
  • Cannabis derivatives do not pass easily from blood into saliva; therefore, potential sensitivity issues for general screening
  • High values are registered in the 1st hour after consumption in the case of inhalation
If there is no direct contamination of the buccal cavity, it depends on the transfer of analytes from the blood into the oral fluid
Sweat
  • Easy to collect and non-invasive
  • Point-of-care tests available
  • Sweat collection patches for drug-use monitoring are available
  • Currently available test kits are expensive and not commonly used
  • Small sample volumes
  • Requires a very sensitive analytical method
  • High chances of external contamination
  • Interpretation of results is difficult
Sample can be easily contaminated from the environment
Hair
  • Provides a history of drug use
  • Sample stable for years
  • Sample collection is non-invasive
  • Extremely useful for crime-related investigation and drug consumption
  • Can be easily contaminated from the environment
  • Analysis requires specialized laboratory
  • Not suitable for point-of-care testing
  • Analysis is expensive
  • Sample collection is dependent on the length of hair
  • Interpretation of result is limited
  • Can be influenced by dyeing and perming treatment
Does not show recent intake
Table 3. Detection window of cannabinoids in urine, blood, and oral fluid specimens.
Table 3. Detection window of cannabinoids in urine, blood, and oral fluid specimens.
Matrix Analyte Cutoff (ng/mL)UseDetection TimesReference
Urine THC-COOH15Single-use<3 days[37,65,96]
THC-COOHModerate use—four times a week<4 days
THC-COOHChronic use14–90 days
BloodTHC10Single-use<5 h[65,96]
THC
THC-COOH
Chronic use<14 days[96]
THC-COOHSingle-use<36 h[65]
Oral fluidTHC
CBD
CBN
THC-COOH
0.5Single and chronic useTHC: 12–34 h
CBD: 1–22 h
CBN: 1–13.5 h
[96,97,98,99,100,101,102]
CBG1Single-use15 min[101]
THCV0.4Single-use15 min
THCA-A1Single-use<90 min
Abbreviations: Δ9-tetrahydrocannabinol (THC); cannabidiol (CBD); cannabinol (CBN); cannabigerol (CBG); tetrahydrocannabivarin (THCV); tetrahydrocannabinolic acid (THCA).
Table 4. Collection methods of oral fluid specimens [41].
Table 4. Collection methods of oral fluid specimens [41].
Method of CollectionAdvantageDisadvantage
Passive drool
  • Accurately reflects drug concentration
  • Does not require special training and tools
  • Can be unpleasant for the donor
  • Slow process
  • Low drug stability without the use of buffers
  • THC binds to plastic containers
Expectoration
  • Provides clean oral fluid, which can increase assay sensitivity
  • Cheaper in comparison with other methods
  • Can be unpleasant for donors and collectors
  • Contains impurities
  • Samples need to be centrifugated before analysis
  • Low recovery when collected in plastic containers and without the use of buffers
  • Lower drug stability without the use of buffers
  • Sample filtration is required when it is used in laboratory analysis
Salivary stimulation
  • Increased sample volume
  • In case of dry mouth, is effective in collecting enough volume
  • Lower pH due to stimulation
  • Increased bicarbonate and ions concentration
  • Lower drug concentration
Collection device
  • Hygienic
  • Requires little time for collection
  • Standard collection devices have buffers inside the collection tube
  • Sample collected in sponge or pad also filtrates the sample
  • Newer collection devices include a volume adequacy indicator
  • Multiple sample collections with the same properties
  • Buffers and surfactants can interfere with laboratory methods of screening
  • Sample is diluted due to the use of buffers
  • Can produce ion suppression or enhancement
  • Recovery of cannabinoids may differ with the use of different buffers
Table 5. Description of collection devices of oral fluid specimens.
Table 5. Description of collection devices of oral fluid specimens.
Device (Manufacturer, City and Country)ComponentsCollection MethodVolume IndicatorOral Fluid Volume (mL)Extraction TechniqueTetrahydrocannabinol (THC) Recovery (%)Refs.
Certus (Concateno, Corston, UK)Pad, container, buffer (3 mL), volume adequacy indicatorAbsorbent pad is inserted into the bufferYes1Pad placed in the buffer for 24 h at 4 °C54
37–44 (71–85)
[112,113]
Cozart (Cozart Bioscience, Abingdon, UK)Pad, container, buffer (2 mL), volume adequacy indicatorAbsorbent pad is inserted into the bufferYes1Elute with a proprietary buffer96
75.9 (6.2)
94.5 (0.02)
67.4
[114,115,116,117,118]
DCD 5000 (Dräger, Lübeck, Germany)Cassette: tap, pad, container, buffer, volume adequacy indicator
Device: reader, printer (electronic and printed results)
Absorbent pad is part of a device; buffer is added after collectionYes 0.38Placed in isopropanol for 1 h and centrifuged89.8–93.8[119,120]
DrugWipe 5, 5S, 6, 6S (Securetec, Neubiberg, Germany)Cassette: collection pad, buffer, LFI stripSweep the tongue, saliva was collected by a change of color, not quantitativeNo---[121]
Greiner (Greiner Bio-One GmbH, Greinerstraße, Austria)Rinsing solution (6 mL), OF extraction solution (4 mL), collection beaker, 2 OF vacuum transfer tubesCollection by thoroughly rinsing out the oral cavity (2 min), expectoration into collection beaker, transfer to Saliva Transfer Tubes, add stabilizersNo Determined spectrophotometrically w/dye in the extraction solutionDetermined spectrophotometrically w/dye in the extraction solution73.6 (4.3)[36,115]
Intercept (OraSure Technologies, Bethlehem, PA, USA)Cotton fiber pad, plastic container, buffer (0.8 mL)Absorbent pad is inserted into the bufferNo 1 mL maxCentrifuged to recover the buffer-oral fluid mixture
Centrifuged to recover the buffer-oral fluid mixture
Centrifuge, add 2 mL methanol to stabilization buffer and pad, incubate and shake 15 min, centrifuge
37.6
31.2–57.2
Additional
19.2–34.4
37.6
39.2
[115,116,122,123,124]
Quantisal (Immunalysis, Pomona, CA, USA)Cellulose pad, plastic container, buffer (3 mL), volume adequacy indicatorAbsorbent pad is inserted into the bufferYes 1 ± 0.1 (10%)Buffer-oral fluid mixture separated with serum separator tube
Pad placed in the buffer for 24 h at 4 °C
81.3–91.4
94
55.8
55.8
(12.0)
81.3–94.4
(4.8–12.1)
74–80 (12–16)
[44,57,112,113,115,125]
OraCol and OraCol Plus (Malvern Medical Developments, Worcester, UK)Foam swab, microtube, centrifuge tubeSaliva is collected by rubbing the sponge swab firmly along the gum until the sponge is wetNo 1Centrifugation with a tube inserted<12.5[36,115]
OraTect III (Branan Medical Corporation, Irvine, CA, USA)Cassette: collection pad, LFI stripDirectly applied to the mouthNo ---[126]
OraTube (Varian, Palo Alto, CA, USA)Pad, plastic container, expresserAbsorbent padNo1.979 mL (in vitro)--[115]
Salicule (Acro Biotech, Montclair, NJ, USA)Expectoration straw, container marker w/scaleExpectorationYes---[36]
Saliva-Sampler (StatSure Diagnostic System, Sterling, VA, USA)Cellulose pad, plastic container, buffer (1 mL), volume adequacy indicatorAbsorbent pad, bufferYes1Buffer-oral fluid mixture extracted from the pad with filter85.4
65.5–68.1
85.4 (7.0)
100–106 (5–6)
[36,113,115,127]
Salivette (Sarstedt AG & Co., Nümbrecht, Germany)Cotton swab, plastic containerCotton swab is chewed, placed back into the container then centrifugedNo UnknownCentrifugation with a tube inserted<12.5[115,128]
Table 6. Detection of cannabinoids in oral fluid specimens in lab-based techniques.
Table 6. Detection of cannabinoids in oral fluid specimens in lab-based techniques.
Analytical MethodCollection DeviceOral Fluid (OF) Sample VolumeExtraction MethodDerivatizationAnalytes Detected (µg/L)Detection Range (µg/L)Refs.
LC-MSPlastic tube200 µL of expectorated OFLiquid-liquid extractionNoneTHC: 2THC: 2–250[133]
LC-MSSalivette500 µL of Salivette OFSPENoneTHC: 2THC: 2–100[134]
LC-MS/MSIntercept100 µL OF or 500 µL of Intercept OFLiquid-liquid extractionNoneTHC: 0.5
for 100 µL sample
THC: 0.5–100[135]
GS-MS/MSIntercept100 µL of Intercept OFSPEHFIP and PFAATHC-COOH: 10THC-COOH: 10–240[136]
2D-GC-MSQuantisal1 mL of Quantisal OFSPEHFIP and TFAATHC-COOH: 2THC-COOH: 2–160[64]
GS-MSQuantisalUnspecified vol. of quantisal OFSPEBSTFATHC: 0.5
CBD: 0.5
CBN: 1
THCAA
THC: 1–16
CBD: 1–16
CBN: 1–16
[137]
LC-QTOF-MSPlastic tube500 µL of synthetic OFLiquid-liquid extractionNoneTHC: 0.05, 0.1
THC-COOH: 0.2, 0.1
THC: 0.1–100
THC-COOH: 0.1–100
[138]
LC-MSPlastic tube500 µL of expectorated OFSPENoneTHC: 2, 5THC: 5–2000[89]
2D-GC-MS (NICI for THC-COOH)Quantisal1 mL of Quantisal OFSPEBSTFA
TFAA (for
THC-COOH)
THC: 0.5
11-OH-THC: 0.4, 0.5
THC-COOH: 6, 7.5
CBD: 0.5
CBN: 1
THC: 0.5–50
11-OH-THC: 0.5–50
THC-COOH: 7.5–500
CBD: 0.5–50
CBN: 1–50
[139]
LC-MS/MSIntercept400 µL of Intercept OFSPENoneTHC: 0.2
THC-COOH: 0.2
THC: 0.25–8
THC-COOH: 0.25–8
[140]
LC-MS/MSQuantisal1 mL of Quantisal OFSPETriphenylphosphine, 2-picolylamine and 2,2′-dypyridyl disulfideTHC: 0.6, 1
THC-COOH: 6, 10
THC: 1–100
THC-COOH: 10–1000
[141]
LC-MS/MS
(quadrupole/orbital)
Plastic tube400 µL of OF in preservation bufferLiquid-liquid extraction and SPENoneTHC: 2 (1 point calibration)
THC-COOH: 7.5
THC-COOH: 7.5–300[102]
LC-MS/MSPlastic tube200 µL of expectorated OFLiquid-liquid extractionNoneTHC: 1THC: 1–500[142]
LC-MS/MSPlastic tube250 µL of expectorated OFDilute and shootDansyl chlorideTHC: 0.005, 0.025
THC-COOH: 2.5
THC: 0.2–20[143]
LC-MS/MSPlastic tube250 µL of expectorated OFSPENoneTHC: 0.1
11-OH-THC: 0.1
THC-COOH: 0.1
CBD: 0.1
CBN: 0.1
THC: 0.1–50
11-OH-THC: 0.1–50
THC-COOH: 0.1–50
CBD: 0.1–50
CBN: 0.1–50
[144]
LC-HRMSOral-Eze, Quantisal250 µL of Oral-Eze and 500 µL of Quantisal OFSPENoneTHC: 0.5
THC-COOH: 9, 12
CBD: 0.5
CBN: 0.5
THC: 0.5–50
THC-COOH: 12–1020
CBD: 0.5–50
CBN: 0.5–50
[145]
LC-MS/MSQuantisal1 mL of Quantisal OFSPENoneTHC-COOH: 9, 12THC-COOH: 12–1020[146]
LC-MS/MSPlastic tube225 µL of expectorated OFMEPSNoneTHC: 0.08, 0.25
11-OH-THC: 0.12, 0.4
THC-COOH: 8, 20
CBD: 0.1, 0.3
CBN: 0.12, 0.3
THC: 0.25–250
11-OH-THC: 0.4–250
THC-COOH: 20–1000
CBD: 0.3–250
CBN: 0.3–250
[147]
LC-MS/MSStatSure, Quantisal100 µL of StatSure
200 µL of Quantisal or Certus OF
Liquid-liquid extractionNoneTHC: 5THC: 5–320[113]
LC-MS/MSQuantisal1.5 µL of combined Quantisal sample/methanol extractSPENoneTHC: 0.3, 0.5
11-OH-THC: 0.2, 0.5
THC-COOH: 50, 80
CBD: 0.3, 0.5
CBN: 0.3, 0.5
THCAA
THC: 0.5–75
11-OH-THC: 0.5–75
THC-COOH: 50–500
CBD: 0.5–75
CBN: 0.5–75
[148]
GC-MS/MSQuantisal,
Oral-Eze
1 mL of Quantisal or 750 µL of Oral-Eze OFSPEHFIP and TFAATHC-COOH: 7.5, 10THC-COOH: 10–1000[149]
LC-MS/MSQuantisal1 mL of Quantisal OFSPENoneTHC: 0.1, 0.2
11-OH-THC: 0.1, 0.2
THC-COOH: 15
CBD: 0.1, 0.2
THCV
CBG
THC: 0.2–100
11-OH-THC: 0.2–50
THC-COOH: 15–3750
CBD: 0.2–50
[123]
Abbreviations: 11-OH-THC: 11-hydroxy-tetrahydrocannabinol; 2D-GC-MS: 2D gas chromatography-mass spectrometry; BSTFA: N,O-bis(trimethylsilyl)trifluoroacetamide; CBD: cannabidiol; CBG: cannabigerol; CBN: cannabinol; GC-MS/MS: gas chromatography-tandem mass spectrometry; GC-MS: gas chromatography-mass spectrometry; HFIP: 1,1,1,3,3,3-hexafluoro-2-propanol; LC-HRMS: liquid chromatography-high resolution mass spectrophotometry; LC-MS/MS: liquid chromatography-tandem mass spectrometry; LC-MS: liquid chromatography–mass spectrometry; LC-QTOF-MS: liquid chromatography-quadrupole time-of-flight mass spectrometry; MEPS: microextraction by packed sorbent; PFAA: pentafluoro propionic anhydride; SPE: solid-phase extraction; TFAA: trifluoroacetic anhydride; THC: Δ9-tetrahydrocannabinol; THCAA: Δ9-tetrahydrocannabinol acid; THC-COOH: 11-nor-9-carboxy-tetrahydrocannabinol; THCV: tetrahydrocannabivarin.
Table 7. Detection of cannabinoids in oral fluid specimens in on-site point-of-care biosensors [36,103].
Table 7. Detection of cannabinoids in oral fluid specimens in on-site point-of-care biosensors [36,103].
Manufacturer (City, Country)DeviceYearInterpretation of ResultDevice Cutoff (THC ng/mL)Laboratory Cutoff (ng/mL)Oral Fluid ConfirmationSensitivity (%)Specificity (%)Accuracy (%)Refs.
Cozart (Abingdon, UK)RapiScan2007Instrumental600-HPLC/GC-MS-100100[102]
Cozart DDSV2009Visual-0.5GC-MS41.210060[150]
Cozart DDS 8062011Instrumental311UPLC-MSMS
GC-MS
2210071[151]
2012Instrumental3110UPLC-MSMS28.210078.7[51]
Cozart DDS2012Instrumental311UPLC-MSMS
GC-MS
37.810094.3[152]
Mavand (Eschweiler, Germany)RapidSTAT2010Visual/Instrumental151.6GC-MS858786.7[153]
2011Visual151GC-MS
UPLC-MSMS
68
56
89
90
86
78
[154]
[151]
2012Visual151
2 *
10
GC-MS
GC-MS
UPLC-MSMS
72
71
43.3
97
55
88.3
93
66
78.2
[152]
[155]
[51]
Biosensor (München, Germany)BIOSENSE Dynamic2011InstrumentalUnknown1UPLC-MSMS
GC-MS
50Not reported51[151]
Sun Biomedical (Blackwood, NJ, USA)OraLine2006Visual41HPLC/GC-MS699274[156]
OraLine IV2007Visual1001HPLC/GC-MS1003654.3[102]
Varian (Palo Alto, CA, USA)OraLab2007Visual1001HPLC/GC-MS4010076[102]
OraLab2007Visual12LC-MS93.398.698.1[157]
OraLab 62011Visual501UPLC-MSMS GC-MS169961[151]
Innovacon (San Diego, CA, USA)OrAlert2011Visual1001UPLC-MSMS GC-MS1110078[151]
OrAlert2012Visual10010UPLC-MSMS23.110090.9[51]
Branan (Irvine, CA, USA)Oratect2007Visual1001HPLC/GC-MS010077.8[102]
Oratect III2011Visual401UPLC-MSMS GC-MS3210041[151]
American Bio Medica (Kinderhook, NY, USA)OralStat2007Visual251HPLC/GC-MS7010091.4[102]
LifePoint (Ontario, CA, USA)Impact2007Instrumental151HPLC/GC-MS10033.371.4[102]
Ulti-Med (Ahrensburg, Germany)SalivaScreen2007Visual>1001HPLC/GC-MS-100100[102]
OraSure Technologies (Bethlehem, PA, USA)Uplink2007Instrumental251HPLC/GC-MS1009295.6[102]
Securetec (Neubiberg, Germany)DrugWipe2007Visual301HPLC/GC-MS8010082.9[102]
DrugWipe 52008Visual302GC-MS529185[158]
DrugWipe2011Visual301GC-MS439688[154]
DrugWipe2012Visual301GC-MS479993[152]
DrugWipe5/5+2011Visual301GC-MS438782[159]
DrugWipe 5A2016Visual300.6 ng/padHS-SPME/GC-MS298853[160]
DrugWipe 52010Visual302 *GC-MS715063[155]
DrugWipe 5+2013Visual30UnknownGC-MS889488[161]
Dräger (Lübeck, GermanyDrugTest 50002006Instrumental200.5LC–MS–MS539455.5[162]
DrugTest 50002010Instrumental202 *GC-MS82.560.579[155]
DrugTest 50002011Instrumental51UPLC-MSMS GC-MS599682[151]
DrugTest 50002012Instrumental5UnknownGC–MS914385.5[161]
DrugTest 50002012Instrumental50.52D-GC-MS
GC-MS
87.781.285.5[102]
DrugTest 50002012Instrumental51GC-MS929797[152]
DrugTest 50002012Instrumental510UPLC-MSMS819692[51]
Alere (North Chicago, IL, USA)DDS 22017Instrumental251LC–MS/MS9010097.5[163]
Abbreviations: OF—oral fluid; THC–Δ9—tetrahydrocannabinol; 2D-GC—2-dimensional GC; GC—gas chromatography; HPLC—high-performance LC; LC—liquid chromatography; MS—mass spectrometry; UPLC—ultraperformance LC. * blood was used as a reference.
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Trif, C.; Harpaz, D.; Eltzov, E.; Parcharoen, Y.; Pechyen, C.; Marks, R.S. Detection of Cannabinoids in Oral Fluid Specimens as the Preferred Biological Matrix for a Point-of-Care Biosensor Diagnostic Device. Biosensors 2024, 14, 126. https://doi.org/10.3390/bios14030126

AMA Style

Trif C, Harpaz D, Eltzov E, Parcharoen Y, Pechyen C, Marks RS. Detection of Cannabinoids in Oral Fluid Specimens as the Preferred Biological Matrix for a Point-of-Care Biosensor Diagnostic Device. Biosensors. 2024; 14(3):126. https://doi.org/10.3390/bios14030126

Chicago/Turabian Style

Trif, Călin, Dorin Harpaz, Evgeni Eltzov, Yardnapar Parcharoen, Chiravoot Pechyen, and Robert S. Marks. 2024. "Detection of Cannabinoids in Oral Fluid Specimens as the Preferred Biological Matrix for a Point-of-Care Biosensor Diagnostic Device" Biosensors 14, no. 3: 126. https://doi.org/10.3390/bios14030126

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