Detection of Cannabinoids in Oral Fluid Specimens as the Preferred Biological Matrix for a Point-of-Care Biosensor Diagnostic Device
Abstract
:1. Introduction
1.1. Why Is It Important to Perform Cannabinoids Detection?
1.2. Different Types of Cannabinoids
1.3. Preferred Cannabinoids as Targets for Detection
1.4. Existing Challenges in the Detection of Cannabinoids
2. Detection of Cannabinoids
2.1. Conventional Detection Procedure
2.2. Immunoassays in Point-of-Care Biosensors
2.3. Electrochemical Sensors for Point-of-Care Testing
3. Biological Matrices for the Detection of Cannabinoids
3.1. Various Biological Matrices, including Blood and Urine Specimens
3.2. Oral Fluid as the Preferred Biological Matrix
3.3. Collection of Oral Fluid Specimens for Cannabinoids Recovery
3.4. Stability of Cannabinoids within Oral Fluid Specimens
4. Detection of Cannabinoids in Oral Fluid Specimens in Lab-Based Techniques and on-Site Point-of-Care Biosensors
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Analytical Technique | Sensitivity | Blood | Oral Fluid | Urine | Sweat | Breath | Hair | Point-of-Care |
---|---|---|---|---|---|---|---|---|
Immunoassay | High | Yes | Yes | Yes | Yes | No | Yes | Yes |
General spectrophotometry (ultraviolet, infrared, fluorescence, visible) | Low | No | Yes | No | No | No | No | Yes |
Raman | Moderate | No | Yes | No | Yes | No | No | Yes |
Nuclear magnetic resonance | Moderate | Yes | No | Yes | No | No | No | No |
Gas chromatography-mass spectrometry | High | Yes | Yes | Yes | Yes | Yes | Yes | Not yet |
Liquid chromatography-mass spectrometry | High | Yes | Yes | Yes | Yes | No | Yes | Not yet |
High-performance liquid chromatography-mass spectrometry | High | Yes | Yes | Yes | Yes | Yes | Yes | No |
Isotope ratio mass spectrometry | Low | No | No | Yes | No | No | No | No |
Thin-layer chromatography | Low | Yes | Yes | Yes | No | No | No | No |
Gas chromatography–nitrogen phosphorous detector | Moderate | Yes | Yes | Yes | Yes | No | No | No |
Gas chromatography–flame ionization detector | Low | Yes | Yes | Yes | Yes | Yes | No | No |
Liquid chromatography–ultraviolet detector | Low | Yes | No | Yes | No | No | No | No |
Chemiluminescence | High | Yes | Yes | Yes | Yes | Yes | Yes | Not yet |
Electrochemical detector | High | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
Capillary electrophoresis | High | Yes | Yes | Yes | Yes | No | Yes | Yes |
Supercritical fluid chromatography | Moderate | Yes | Yes | Yes | Yes | No | No | No |
Biological Matrix | Advantages | Disadvantage | Cannabinoids Detection |
---|---|---|---|
Blood |
|
| Show recent drug intake |
Urine |
|
| It does not show recent drug intake but offers a view of drug usage over the last month |
Oral fluid |
|
| 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 |
|
| Sample can be easily contaminated from the environment |
Hair |
|
| Does not show recent intake |
Matrix | Analyte | Cutoff (ng/mL) | Use | Detection Times | Reference |
---|---|---|---|---|---|
Urine | THC-COOH | 15 | Single-use | <3 days | [37,65,96] |
THC-COOH | Moderate use—four times a week | <4 days | |||
THC-COOH | Chronic use | 14–90 days | |||
Blood | THC | 10 | Single-use | <5 h | [65,96] |
THC THC-COOH | Chronic use | <14 days | [96] | ||
THC-COOH | Single-use | <36 h | [65] | ||
Oral fluid | THC CBD CBN THC-COOH | 0.5 | Single and chronic use | THC: 12–34 h CBD: 1–22 h CBN: 1–13.5 h | [96,97,98,99,100,101,102] |
CBG | 1 | Single-use | 15 min | [101] | |
THCV | 0.4 | Single-use | 15 min | ||
THCA-A | 1 | Single-use | <90 min |
Method of Collection | Advantage | Disadvantage |
---|---|---|
Passive drool |
|
|
Expectoration |
|
|
Salivary stimulation |
|
|
Collection device |
|
|
Device (Manufacturer, City and Country) | Components | Collection Method | Volume Indicator | Oral Fluid Volume (mL) | Extraction Technique | Tetrahydrocannabinol (THC) Recovery (%) | Refs. |
---|---|---|---|---|---|---|---|
Certus (Concateno, Corston, UK) | Pad, container, buffer (3 mL), volume adequacy indicator | Absorbent pad is inserted into the buffer | Yes | 1 | Pad placed in the buffer for 24 h at 4 °C | 54 37–44 (71–85) | [112,113] |
Cozart (Cozart Bioscience, Abingdon, UK) | Pad, container, buffer (2 mL), volume adequacy indicator | Absorbent pad is inserted into the buffer | Yes | 1 | Elute with a proprietary buffer | 96 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 collection | Yes | 0.38 | Placed in isopropanol for 1 h and centrifuged | 89.8–93.8 | [119,120] |
DrugWipe 5, 5S, 6, 6S (Securetec, Neubiberg, Germany) | Cassette: collection pad, buffer, LFI strip | Sweep the tongue, saliva was collected by a change of color, not quantitative | No | - | - | - | [121] |
Greiner (Greiner Bio-One GmbH, Greinerstraße, Austria) | Rinsing solution (6 mL), OF extraction solution (4 mL), collection beaker, 2 OF vacuum transfer tubes | Collection by thoroughly rinsing out the oral cavity (2 min), expectoration into collection beaker, transfer to Saliva Transfer Tubes, add stabilizers | No | Determined spectrophotometrically w/dye in the extraction solution | Determined spectrophotometrically w/dye in the extraction solution | 73.6 (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 buffer | No | 1 mL max | Centrifuged 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 indicator | Absorbent pad is inserted into the buffer | Yes | 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 tube | Saliva is collected by rubbing the sponge swab firmly along the gum until the sponge is wet | No | 1 | Centrifugation with a tube inserted | <12.5 | [36,115] |
OraTect III (Branan Medical Corporation, Irvine, CA, USA) | Cassette: collection pad, LFI strip | Directly applied to the mouth | No | - | - | - | [126] |
OraTube (Varian, Palo Alto, CA, USA) | Pad, plastic container, expresser | Absorbent pad | No | 1.979 mL (in vitro) | - | - | [115] |
Salicule (Acro Biotech, Montclair, NJ, USA) | Expectoration straw, container marker w/scale | Expectoration | Yes | - | - | - | [36] |
Saliva-Sampler (StatSure Diagnostic System, Sterling, VA, USA) | Cellulose pad, plastic container, buffer (1 mL), volume adequacy indicator | Absorbent pad, buffer | Yes | 1 | Buffer-oral fluid mixture extracted from the pad with filter | 85.4 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 container | Cotton swab is chewed, placed back into the container then centrifuged | No | Unknown | Centrifugation with a tube inserted | <12.5 | [115,128] |
Analytical Method | Collection Device | Oral Fluid (OF) Sample Volume | Extraction Method | Derivatization | Analytes Detected (µg/L) | Detection Range (µg/L) | Refs. |
---|---|---|---|---|---|---|---|
LC-MS | Plastic tube | 200 µL of expectorated OF | Liquid-liquid extraction | None | THC: 2 | THC: 2–250 | [133] |
LC-MS | Salivette | 500 µL of Salivette OF | SPE | None | THC: 2 | THC: 2–100 | [134] |
LC-MS/MS | Intercept | 100 µL OF or 500 µL of Intercept OF | Liquid-liquid extraction | None | THC: 0.5 for 100 µL sample | THC: 0.5–100 | [135] |
GS-MS/MS | Intercept | 100 µL of Intercept OF | SPE | HFIP and PFAA | THC-COOH: 10 | THC-COOH: 10–240 | [136] |
2D-GC-MS | Quantisal | 1 mL of Quantisal OF | SPE | HFIP and TFAA | THC-COOH: 2 | THC-COOH: 2–160 | [64] |
GS-MS | Quantisal | Unspecified vol. of quantisal OF | SPE | BSTFA | THC: 0.5 CBD: 0.5 CBN: 1 THCAA | THC: 1–16 CBD: 1–16 CBN: 1–16 | [137] |
LC-QTOF-MS | Plastic tube | 500 µL of synthetic OF | Liquid-liquid extraction | None | THC: 0.05, 0.1 THC-COOH: 0.2, 0.1 | THC: 0.1–100 THC-COOH: 0.1–100 | [138] |
LC-MS | Plastic tube | 500 µL of expectorated OF | SPE | None | THC: 2, 5 | THC: 5–2000 | [89] |
2D-GC-MS (NICI for THC-COOH) | Quantisal | 1 mL of Quantisal OF | SPE | BSTFA 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/MS | Intercept | 400 µL of Intercept OF | SPE | None | THC: 0.2 THC-COOH: 0.2 | THC: 0.25–8 THC-COOH: 0.25–8 | [140] |
LC-MS/MS | Quantisal | 1 mL of Quantisal OF | SPE | Triphenylphosphine, 2-picolylamine and 2,2′-dypyridyl disulfide | THC: 0.6, 1 THC-COOH: 6, 10 | THC: 1–100 THC-COOH: 10–1000 | [141] |
LC-MS/MS (quadrupole/orbital) | Plastic tube | 400 µL of OF in preservation buffer | Liquid-liquid extraction and SPE | None | THC: 2 (1 point calibration) THC-COOH: 7.5 | THC-COOH: 7.5–300 | [102] |
LC-MS/MS | Plastic tube | 200 µL of expectorated OF | Liquid-liquid extraction | None | THC: 1 | THC: 1–500 | [142] |
LC-MS/MS | Plastic tube | 250 µL of expectorated OF | Dilute and shoot | Dansyl chloride | THC: 0.005, 0.025 THC-COOH: 2.5 | THC: 0.2–20 | [143] |
LC-MS/MS | Plastic tube | 250 µL of expectorated OF | SPE | None | THC: 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-HRMS | Oral-Eze, Quantisal | 250 µL of Oral-Eze and 500 µL of Quantisal OF | SPE | None | THC: 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/MS | Quantisal | 1 mL of Quantisal OF | SPE | None | THC-COOH: 9, 12 | THC-COOH: 12–1020 | [146] |
LC-MS/MS | Plastic tube | 225 µL of expectorated OF | MEPS | None | THC: 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/MS | StatSure, Quantisal | 100 µL of StatSure 200 µL of Quantisal or Certus OF | Liquid-liquid extraction | None | THC: 5 | THC: 5–320 | [113] |
LC-MS/MS | Quantisal | 1.5 µL of combined Quantisal sample/methanol extract | SPE | None | THC: 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/MS | Quantisal, Oral-Eze | 1 mL of Quantisal or 750 µL of Oral-Eze OF | SPE | HFIP and TFAA | THC-COOH: 7.5, 10 | THC-COOH: 10–1000 | [149] |
LC-MS/MS | Quantisal | 1 mL of Quantisal OF | SPE | None | THC: 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] |
Manufacturer (City, Country) | Device | Year | Interpretation of Result | Device Cutoff (THC ng/mL) | Laboratory Cutoff (ng/mL) | Oral Fluid Confirmation | Sensitivity (%) | Specificity (%) | Accuracy (%) | Refs. |
---|---|---|---|---|---|---|---|---|---|---|
Cozart (Abingdon, UK) | RapiScan | 2007 | Instrumental | 600 | - | HPLC/GC-MS | - | 100 | 100 | [102] |
Cozart DDSV | 2009 | Visual | - | 0.5 | GC-MS | 41.2 | 100 | 60 | [150] | |
Cozart DDS 806 | 2011 | Instrumental | 31 | 1 | UPLC-MSMS GC-MS | 22 | 100 | 71 | [151] | |
2012 | Instrumental | 31 | 10 | UPLC-MSMS | 28.2 | 100 | 78.7 | [51] | ||
Cozart DDS | 2012 | Instrumental | 31 | 1 | UPLC-MSMS GC-MS | 37.8 | 100 | 94.3 | [152] | |
Mavand (Eschweiler, Germany) | RapidSTAT | 2010 | Visual/Instrumental | 15 | 1.6 | GC-MS | 85 | 87 | 86.7 | [153] |
2011 | Visual | 15 | 1 | GC-MS UPLC-MSMS | 68 56 | 89 90 | 86 78 | [154] [151] | ||
2012 | Visual | 15 | 1 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 Dynamic | 2011 | Instrumental | Unknown | 1 | UPLC-MSMS GC-MS | 50 | Not reported | 51 | [151] |
Sun Biomedical (Blackwood, NJ, USA) | OraLine | 2006 | Visual | 4 | 1 | HPLC/GC-MS | 69 | 92 | 74 | [156] |
OraLine IV | 2007 | Visual | 100 | 1 | HPLC/GC-MS | 100 | 36 | 54.3 | [102] | |
Varian (Palo Alto, CA, USA) | OraLab | 2007 | Visual | 100 | 1 | HPLC/GC-MS | 40 | 100 | 76 | [102] |
OraLab | 2007 | Visual | 1 | 2 | LC-MS | 93.3 | 98.6 | 98.1 | [157] | |
OraLab 6 | 2011 | Visual | 50 | 1 | UPLC-MSMS GC-MS | 16 | 99 | 61 | [151] | |
Innovacon (San Diego, CA, USA) | OrAlert | 2011 | Visual | 100 | 1 | UPLC-MSMS GC-MS | 11 | 100 | 78 | [151] |
OrAlert | 2012 | Visual | 100 | 10 | UPLC-MSMS | 23.1 | 100 | 90.9 | [51] | |
Branan (Irvine, CA, USA) | Oratect | 2007 | Visual | 100 | 1 | HPLC/GC-MS | 0 | 100 | 77.8 | [102] |
Oratect III | 2011 | Visual | 40 | 1 | UPLC-MSMS GC-MS | 32 | 100 | 41 | [151] | |
American Bio Medica (Kinderhook, NY, USA) | OralStat | 2007 | Visual | 25 | 1 | HPLC/GC-MS | 70 | 100 | 91.4 | [102] |
LifePoint (Ontario, CA, USA) | Impact | 2007 | Instrumental | 15 | 1 | HPLC/GC-MS | 100 | 33.3 | 71.4 | [102] |
Ulti-Med (Ahrensburg, Germany) | SalivaScreen | 2007 | Visual | >100 | 1 | HPLC/GC-MS | - | 100 | 100 | [102] |
OraSure Technologies (Bethlehem, PA, USA) | Uplink | 2007 | Instrumental | 25 | 1 | HPLC/GC-MS | 100 | 92 | 95.6 | [102] |
Securetec (Neubiberg, Germany) | DrugWipe | 2007 | Visual | 30 | 1 | HPLC/GC-MS | 80 | 100 | 82.9 | [102] |
DrugWipe 5 | 2008 | Visual | 30 | 2 | GC-MS | 52 | 91 | 85 | [158] | |
DrugWipe | 2011 | Visual | 30 | 1 | GC-MS | 43 | 96 | 88 | [154] | |
DrugWipe | 2012 | Visual | 30 | 1 | GC-MS | 47 | 99 | 93 | [152] | |
DrugWipe5/5+ | 2011 | Visual | 30 | 1 | GC-MS | 43 | 87 | 82 | [159] | |
DrugWipe 5A | 2016 | Visual | 30 | 0.6 ng/pad | HS-SPME/GC-MS | 29 | 88 | 53 | [160] | |
DrugWipe 5 | 2010 | Visual | 30 | 2 * | GC-MS | 71 | 50 | 63 | [155] | |
DrugWipe 5+ | 2013 | Visual | 30 | Unknown | GC-MS | 88 | 94 | 88 | [161] | |
Dräger (Lübeck, Germany | DrugTest 5000 | 2006 | Instrumental | 20 | 0.5 | LC–MS–MS | 53 | 94 | 55.5 | [162] |
DrugTest 5000 | 2010 | Instrumental | 20 | 2 * | GC-MS | 82.5 | 60.5 | 79 | [155] | |
DrugTest 5000 | 2011 | Instrumental | 5 | 1 | UPLC-MSMS GC-MS | 59 | 96 | 82 | [151] | |
DrugTest 5000 | 2012 | Instrumental | 5 | Unknown | GC–MS | 91 | 43 | 85.5 | [161] | |
DrugTest 5000 | 2012 | Instrumental | 5 | 0.5 | 2D-GC-MS GC-MS | 87.7 | 81.2 | 85.5 | [102] | |
DrugTest 5000 | 2012 | Instrumental | 5 | 1 | GC-MS | 92 | 97 | 97 | [152] | |
DrugTest 5000 | 2012 | Instrumental | 5 | 10 | UPLC-MSMS | 81 | 96 | 92 | [51] | |
Alere (North Chicago, IL, USA) | DDS 2 | 2017 | Instrumental | 25 | 1 | LC–MS/MS | 90 | 100 | 97.5 | [163] |
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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
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 StyleTrif, 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