TY - JOUR
AU1 - da Cunha, Kelly, Francisco
AU2 - Oliveira, Karina, Diniz
AU3 - Huestis, Marilyn, A
AU4 - Costa, Jose, Luiz
AB - Abstract New psychoactive substances (NPS) are a major public health problem, primarily due to the increased number of acute poisoning cases. Detection of these substances is a challenge. The aim of this research was to develop and validate a sensitive screening method for 104 drugs of abuse, including synthetic cannabinoids, synthetic cathinones, fentanyl analogues, phenethylamines and other abused psychoactive compounds (i.e., THC, MDMA, LSD and their metabolites) in oral fluid by liquid chromatography–tandem mass spectrometry (LC–MS-MS). The Quantisal™ oral fluid device was used to collect oral fluid samples. The oral fluid–elution buffer mixture (500-μL sample) was extracted with t-butyl methyl ether, and chromatographic separation was performed on a Raptor™ biphenyl column (100 × 2.1 mm ID, 2.7 μm), with a total run time of 13.5 min. Limits of detection were established at three concentrations (0.05, 0.1 or 1 ng/mL) for most analytes, except for acetyl norfentanyl and mescaline (5 ng/mL). Matrix effects were generally <20% and overall extraction recoveries >60%. The highest matrix effect was observed within the synthetic cannabinoid group (PB22, −55.5%). Lower recoveries were observed for 2C-T (47.2%) and JWH-175 (58.7%). Recoveries from the Quantisal™ device were also evaluated for all analytes (56.7–127%), with lower recoveries noted for 25I-NBOMe, valerylfentanyl and mCPP (56.7, 63.0 and 69.9%, respectively). Drug stability in oral fluid was evaluated at 15, 60 and 90 days and at 25, 4 and −20°C. As expected, greater stability was observed when samples were stored at −20°C, but even when frozen, some NPS (e.g., synthetic cannabinoids) showed more than 20% degradation. The method was successfully applied to the analysis of seven authentic oral fluid samples positive for 17 different analytes. The method achieved good sensitivity and simultaneous detection of a wide range of NPS. Introduction New psychoactive substances (NPS) are synthesized to mimic the effects of traditional illicit drugs, and they frequently pose a public health risk (1). As early as 2005, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) developed the European Union Early Warning System (EWS) for NPS. By 2018, 730 NPS were monitored in Europe, with an additional 55 NPS first detected in that year (2). In addition, the EMCDDA also provides the annual European Drug Report that contains information regarding NPS trafficking (2). The illicit market constantly changes with many intoxications occurring worldwide (3–6). As a result, multiple countries and recently the United Nations Office on Drugs and Crime (UNODC) monitor NPS and provide reports that benefit law enforcement, first responders and health-care providers around the world (1). In the USA, the National Drug Early Warning System (NDEWS) and the Center for Forensic Science Research and Education (CFSRE) publish NPS trend reports from seizure and toxicological analyses, respectively (7, 8), and the UNODC maintains a new worldwide NPS toxicology register and publishes a World Drug Report annually (9). In Brazil, there is no specific source of information about NPS availability and consumption. Drug seizures in 2016–2017 were reported by the Brazilian Federal Police (10). Other data were derived from publications of retrospective studies of seizures (11, 12) or intoxication cases (6). The number of seizures of synthetic drugs by state police in Brazil grew from 49 cases in 2013 to 762 in 2017, with almost 50% of these drugs being NPS (12). The absence of a good source of NPS data restricts strategies for harm prevention programs and acute intoxication treatment protocols. Oral fluid is a highly useful alternative biological matrix for toxicology, especially now for onsite collection in driving under the influence of drug (DUID) cases and for drug treatment and workplace drug testing. Oral fluid was the most common type of specimen collected, as compared to blood and urine samples, for monitoring drug use at electronic music festivals (13). Oral fluid advantages include an observed, non-invasive collection that can be performed onsite by trained non-medical staff, concentrations better reflect blood concentrations than urine, and basic drugs highly concentrate in oral fluid leading to improved sensitivity for drug detection. Disadvantages include smaller collection volumes than urine, lack of correlation with blood immediately after drug inhalation or ingestion due to coating of the mouth with drug and lower concentrations of acidic drugs in oral fluid in comparison with blood. Also, drugs in oral fluid have a shorter window of detection than urine, generally representing more recent drug use (14). Oral fluid drug concentrations are influenced by the pH differences between blood and oral fluid, drug polarity and protein binding. Most drugs transfer into oral fluid by passive diffusion, but also by ultrafiltration of small molecules and secretion of only a few, such as lithium (15). Methods to detect NPS in biological matrices are challenging due to the large number of substances to monitor and their low concentrations due to their high potencies. Immunoassays are often utilized for screening purposes, but the time required to develop a new immunoassay and the rapid turnover of available NPS mean that immunoassays rapidly become out of date due to the constant introduction of different NPS. Also, many NPS analytes and their metabolites are structurally similar and may cross-react in an immunoassay. A more selective assay that can be developed more quickly to identify NPS is greatly preferred. Liquid chromatography–tandem mass spectrometry (LC–MS-MS) is a technique with much higher selectivity than immunoassays and can analyze multiple NPS classes in the same assay (16). The aim of this research was to develop a sensitive screening method to detect 104 NPS and other drugs of abuse in oral fluid samples by LC–MS-MS. Analytes were included to monitor NPS consumption at college parties and electronic music festivals. Collecting non-invasive oral fluid onsite increases the probability of understanding the patterns of NPS consumption in these populations (17). Experimental Standard chemicals All drug standards were purchased from Cayman Chemical (Ann Arbor, MI, USA) or Cerilliant (Round Rock, TX, USA). Acetonitrile, methanol and formic acid (98–100%) were acquired from Merck (Darmstadt, Germany) and Scharlau (Barcelona, Spain). MTBE (t-butyl methyl ether) was obtained from Sigma-Aldrich (St. Louis, MO, EUA) and sodium tetraborate from L.S. Chemicals (Ribeirao Preto, SP, Brazil). Ultrapure deionized water was supplied by a Milli-Q RG unit from Millipore (Billerica, MA, USA). All solvents employed in the extraction were HPLC grade. Quantisal™ oral fluid collection devices and elution buffer were purchased from Immunalysis (Pomona, CA, USA). Working standard and internal standard solutions Initially, individual stock solutions were prepared by dilution of reference materials in methanol. Four working solutions (100, 10, 1 and 0.5 ng/mL as free base) were prepared by combining aliquots of the individual stock solutions in methanol. Three of these working solutions were utilized to fortify blank oral fluid samples at the limits of detection for all analytes. One of them was used in the matrix effects, stability and recovery experiments. The working standard solutions were prepared containing a maximum of two groups (synthetic cannabinoids and cathinones, fentanyl analogues and 2C-X, NBOMes/NBOHs and other drugs of abuse). The internal standard mixture (THC-d3 50 ng/mL, diazepam-d5 50 ng/mL, MDMA-d5 20 ng/mL, LSD-d3 20 ng/mL, fentanyl-d5 200 ng/mL and morphine-d5 200 ng/mL) was prepared by appropriate dilution in methanol. All solutions were stored at −20°C in amber glass vials. Quantisal™ oral fluid devices were used for all onsite sample collections and the device recovery experiments. One-milliliter oral fluid ±10% was collected and mixed with 3-mL Quantisal™ elution buffer. Extraction procedure A liquid–liquid extraction (LLE) was performed with 500-μL oral fluid-Quantisal™ elution buffer, 25-μL internal standard mixture, 500-μL saturated sodium tetraborate aqueous solution and 2-mL MTBE. The sample was vortexed (2 min) and centrifuged (4,500 rpm/5 min), with 1.7-mL organic phase evaporated under nitrogen (40°C) and reconstituted with 100-μL methanol, and 2 μL were injected into LC–MS-MS system. Instrumentation The analysis was performed on a Nexera UHPLC chromatographic system coupled to a LCMS8060 triple quadrupole mass spectrometer (Shimadzu, Kyoto, Japan). The chromatographic separation was performed with a Raptor™ biphenyl column (100 × 2.1 mm, 2.7 μm; Restek, Bellefonte, PA, USA), maintained at 40°C. The mobile phase consisted of ultrapure water (A) and methanol (B), both containing 0.1% formic acid (v/v) and 2 mmol/L ammonium formate. The flow rate was 0.4 mL/min, with the elution gradient initialized at 5% B, followed by a linear increase to 100% B over 9 min, held at 100% B for 2 min, returning to initial conditions over 0.2 min and held at 5% B for 2.3 min for column re-equilibration. The total run time was 13.5 min. The mass spectrometer was equipped with an electrospray ionization source (ESI), operated in positive ion mode. The optimized source parameters were heat block temperature 400°C; ion spray voltage 4.0 kV; nebulizer gas (N2) flow 3 L/min; desolvation line temperature 250°C; drying gas (N2) flow 10 L/min; heating gas (N2) flow 10 L/min; interface temperature 300°C; and collision-induced dissociation gas pressure (Ar) 270 kPa. The analyses were performed in multiple reaction monitoring (MRM) mode. For each compound, two MRM transitions were selected as qualifiers for identification (Supplementary Table 1). Data were acquired and processed with the LabSolutions 5.97 software (Shimadzu, Kyoto, Japan). Method validation This method was validated following the Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines for qualitative analysis. Evaluated parameters were limit of detection (LOD), recovery, matrix effects, interference studies, carryover and stability (18). All experiments evaluated two NPS classes at a time. Limit of detection Three different concentrations of each analyte were evaluated (0.05, 0.1 and 1 ng/mL) to establish the LOD. Three blank oral fluid samples from different donors were fortified at these concentrations in duplicate, extracted and analyzed over 3 days (n = 18 for each analyte and each concentration). The LOD was determined as the lowest concentration that fully met the following identification criteria: response at least three times the signal-to-noise ratio of blank samples, retention time within ±0.2 min and the ratio of the two transitions within a maximum of ±30% of that established for the working standard solution, varying more for those with low intensity for the major transition (19). Interference studies Blank oral fluid samples were fortified with common pharmaceuticals at 5,000 ng/mL in duplicate, properly diluted in Quantisal™ elution buffer, extracted and injected into the LC–MS-MS. No peaks were visualized in each analyte’s detection window that satisfied LOD criteria. Supplementary Table 2 includes all the pharmaceuticals evaluated. Ten blank oral fluid samples from different sources were extracted and analyzed to evaluate possible matrix interferences. No interfering peaks were visualized that satisfied LOD criteria. Potential contribution of native ions present in commercial deuterated internal standards was evaluated comparing the blank oral fluid pool with and without internal standard additions. Carryover Blank oral fluid samples diluted in the Quantisal™ elution buffer were analyzed after injection of fortified samples containing 10 ng/mL of each analyte in their specific working standard solutions (see Working Standard and Internal Standard Solutions). Carryover was evaluated for each analyte in the blank oral fluid sample to document that identification criteria (retention time, peak chromatographic shape and MRM ion ratio criteria) were not met. If identification criteria were met for any drug that was positive in the preceding sample fortified at 10 ng/mL, the following sample was re-extracted and analyzed in the method. Matrix effect A batch composed of 10 blank oral fluid samples from different sources, properly diluted in Quantisal™ elution buffer, was extracted and fortified with the working and internal standard solutions prior to the evaporation step. The average absolute peak area was compared with the average absolute peak area of a neat solution containing the working and internal standards and injected six times. The experiment was performed at 10 ng/mL. Recovery Extraction recovery was determined with two different batches of samples. The first was composed of 10 blank oral fluid samples from different sources, diluted in Quantisal™ elution buffer, that were extracted and fortified with the working and internal standard solutions prior to the evaporation step; the second batch contained 10 blank oral fluid samples from different sources and diluted in Quantisal™ elution buffer that were fortified with the working and internal standard solutions prior to the extraction procedure. Both sets were fortified at 10 ng/mL. The average absolute peak area in the first batch was considered as 100% of extraction recovery, and it was compared with the average absolute peak area in the second batch to estimate the extraction recovery for each analyte. To evaluate the Quantisal™ oral fluid device recovery (20), 9-mL pooled blank oral fluid sample from five different sources was fortified with 1-mL working standard solution mixture at 100 ng/mL and divided into two batches. The first was transferred to five conical glass tubes, and one Quantisal device™ inserted into each until the volume indicator turned blue indicating 1 ± 0.1 mL of oral fluid collected according to the manufacturer’s instructions. The devices were removed from the oral fluid and placed into the elution buffer for 12 h, maintained at 4°C. The second half of the fortified oral fluid sample was transferred to a polypropylene tube containing the Quantisal™ elution buffer for a 1:3 ratio and generated five replicates for further analysis. All samples were refrigerated (4°C) over 12 h. Five replicates of 500 μL were extracted as described above. The average relative peak area was compared across batches to determine device recovery for each analyte. The experiment was executed for groups of NPS, with no more than two classes/sets. Prior to the experiment, the pool of blank oral fluid sample was analyzed with and without the internal standard mixture to ensure that there were no interferences from the matrix. Stability Long-term stability was evaluated for 15, 60 and 90 days at 25, 4 and −20°C. Blank oral fluid samples were fortified individually by NPS groups, diluted in Quantisal™ elution buffer and aliquoted in triplicate. Triplicates were extracted and analyzed immediately as day 0 or baseline concentrations. The other replicates were stored at the three temperatures for different periods of time. At 15, 60 and 90 days, triplicate samples were extracted and analyzed. The average relative peak area on each day was compared with the average relative peak area of day 0. Proof of concept To demonstrate that the analytical method was fit for purpose, oral fluid samples collected from volunteers present at electronic music festival in December 2019 were analyzed (n = 7). The inclusion criteria were age >18 years old and self-report use of synthetic drug in the last 24 h. The sample collection was performed anonymously, and procedures performed in this study involving oral fluid samples from human volunteers were in accordance with the ethical standards of the University of Campinas committee (Comitê de Ética em Pesquisa da UNICAMP—CEP; CAAE 88770318.0.0000.5404) and with the ethical standards as laid down in the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Results and Discussion There are no regulated cutoffs for NPS in oral fluid samples. The available cutoffs are for traditional drugs of abuse (e.g., SAMHSA Mandatory Guidelines) and for driving under the influence of drug testing (14). NPS were found in low concentrations in blood, suggesting that it was important to reach low LODs in oral fluid. The different NPS classes studied have varying chemical structures, which challenged the selection of a suitable organic solvent for LLE. MTBE, a non-polar solvent, was selected as the extraction solvent in order to achieve good recovery for most of the studied NPS and common drugs of abuse. Unfortunately, benzoylecgonine (cocaine’s major metabolite) had poor recovery using this extraction solvent and was not included in the method. The poor recovery of benzoylecgonine in LLE was reported in previous published methods (21, 22). The 13.5-min run time was also important to guarantee a good chromatographic resolution for most analytes, including some position isomers. Figure 1 shows the chromatogram of all analytes at 1 ng/mL and the internal standard mixture chosen for all analyses. Figure 1 Open in new tabDownload slide Extracted ion chromatogram of fortified oral fluid at 1 ng/mL of each analyte and six internal standards. Figure 1 Open in new tabDownload slide Extracted ion chromatogram of fortified oral fluid at 1 ng/mL of each analyte and six internal standards. Most analytes achieved LODs of 0.05 or 0.1 ng/mL (Table I). Only acetyl norfentanyl and mescaline had LODs higher than 1 ng/mL. There are no published works documenting acetyl norfentanyl oral fluid concentrations. Data from fatal intoxications showed that the average concentration ranged from 1 to 53 ng/mL in blood, depending upon whether more than one substance was detected (23). Five authentic cases had an average concentration of 44 ng/mL in postmortem whole blood (24). Table I Limits of Detection, Matrix Effects and Recoveries of 104 New Psychoactive Substances and Other Drugs of Abuse in Oral Fluid Samples by LC–MS-MS Group . Analyte . LOD (ng/mL) . Matrix effect (%) (n = 10) . Recovery (%) . Extraction (n = 10) . Quantisal™ (n = 5) (%RSD) . Fentanyl analogues Acetyl fentanyl 0.05 −7.7 103 96.0 (8.5) Acetyl norfentanyl 5 13.4 8.2 94.3 (9.7) Acrylfentanyl 0.05 −14.5 97.0 87.7 (6.8) Alfentanil 0.1 11.0 113 95.7 (6.7) Carfentanil 0.05 −5.9 110 88.5 (7.2) Fentanyl 0.05 −15.9 100 90.9 (7.0) Furanylfentanyl 0.05 −13.7 102 84.3 (7.8) Norfentanyl 1 −16.1 25.4 89.1 (8.8) Remifentanil 0.1 −17.6 114 74.7 (8.4) Sufentanil 0.1 −0.7 100 86.9 (9.1) Thiofentanyl 0.05 −3.6 103 94.6 (7.1) Valerylfentanyl 0.05 −8.8 102 63.0 (7.1) Synthetic cannabinoids AB-FUBINACA 0.1 14.1 82.9 109 (11.3) AB-PINACA 0.05 10.8 80.3 100 (13.8) APINACA 0.05 −31.3 61.4 120 (9.6) AM2201 0.05 −19.6 72.3 106 (10.1) AM2233 1 34.3 81.0 86.2 (10.4) HU-211 1 25.9 78.1 103 (10.0) JWH-015 0.05 −40.0 76.5 96.4 (12.1) JWH-019 0.05 −29.6 62.6 122 (9.5) JWH-073 0.05 −23.5 70.2 109 (10.1) JWH-081 0.05 −15.1 66.3 110 (9.0) JWH-122 0.05 −40.2 61.9 113 (9.4) JWH-175 0.05 −43.1 58.7 124 (12.1) JWH-200 0.05 10.4 79.0 96.8 (13.1) JWH-203 1 −17.4 68.9 103 (9.3) JWH-210 0.05 −37.1 64.0 126 (6.1) JWH-250 1 −18.0 71.4 98.7 (9.7) RCS-4 0.05 −22.4 70.0 99.2 (11.2) RCS-8 0.05 −29.2 64.7 117 (9.1) XLR11 0.1 −14.7 68.8 90.4 (10.6) JWH-176 1 0.8 60.4 127 (9.0) PB22 0.05 −55.5 76.8 90.0 (12.3) MMB-FUBINACA 0.05 −15.5 73.2 87.2 (1.9) Synthetic cathinones Cathinone 1 −9.1 64.5 91.5 (3.6) Methcathinone 1 −10.1 76.1 92.8 (1.2) Butylone 0.05 0.9 81.3 94.9 (3.3) Pentylone 0.05 16.9 85.5 92.7 (3.9) N-ethylpentylone 0.05 −0.2 83.8 93.8 (2.0) Mephedrone 0.05 2.9 80.3 93.7 (2.6) Methedrone 1 −11.8 75.9 92.8 (2.1) Pentedrone 1 −12.3 83.0 93.6 (1.8) Benzedrone 0.05 −8.7 83.2 88.5 (3.3) 4-Chloroethcathinone 0.05 15.6 82.9 91.8 (2.8) Dipentylone 0.1 −0.3 84.2 92.3 (3.8) Dimethylone 1 −8.2 83.7 93.4 (2.9) MDPV 0.05 10.3 83.3 95.0 (1.8) Ethylone 0.05 0.4 81.8 93.0 (1.5) Methylone 0.05 13.0 77.1 92.9 (2.6) Alpha-PVP 0.05 6.9 84.5 91.6 (3.0) Pyrovalerone 0.05 10.4 84.7 93.6 (3.3) Naphyrone 0.05 0.3 82.0 88.0 (4.7) 4-Fluoromethcathinone 1 8.4 80.2 92.2 (2.6) Phenethylamines 25B-NBOH 0.1 −6.0 79.4 79.1 (4.8) 25B-NBOMe 0.1 −16.1 71.6 70.9 (3.8) 25C-NBOH 0.1 −15.6 82.0 83.4 (5.5) 25C-NBOMe 0.05 −12.4 74.3 77.1 (5.1) 25D-NBOMe 0.1 −16.6 70.5 84.1 (4.9) 25E-NBOH 0.05 10.3 75.5 82.9 (10.7) 25E-NBOMe 0.1 −4.8 70.2 69.2 (7.2) 25G-NBOMe 0.1 −9.3 70.6 69.2 (6.6) 25H-NBOMe 0.05 −0.7 84.8 91.8 (5.4) 25I-NBOH 0.05 19.0 77.8 73.1 (7.0) 25I-NBOMe 0.05 29.0 71.3 56.7 (6.5) 25N-NBOMe 0.05 20.1 84.2 89.0 (4.6) 25T2-NBOMe 0.05 −0.6 78.6 78.0 (5.9) 2C-B 1 23.0 82.8 90.8 (10.1) 2C-C 1 6.0 78.2 72.4 (7.8) 2C-D 0.1 −13.1 66.2 90.2 (7.2) 2C-E 1 −17.0 78.9 89.2 (7.9) 2C-G 1 3.3 78.7 86.2 (8.7) 2C-I 0.1 −18.2 82.6 84.5 (7.4) 2C-T 1 −14.6 47.4 91.8 (9.8) 2C-T-2 1 7.5 63.2 85.6 (8.9) 2C-T-4 0.1 −18.4 71.6 90.7 (8.7) Other NPS and drugs of abuse LSD 0.05 −14.1 86.8 87.3 (4.5) Amphetamine 1 6.6 65.3 97.8 (5.0) Methamphetamine 1 6.8 74.0 97.2 (6.3) MDA 1 −1.5 67.7 99.9 (4.4) MDMA 1 −3.7 74.7 97.8 (4.7) MDEA 1 −3.4 83.6 97.9 (6.2) PMA 1 −11.4 60.2 97.5 (6.2) 4-MTA 1 −17.1 90.0 95.1 (5.4) DOET 1 −15.5 81.1 96.3 (5.7) DOM 1 2.4 78.1 93.3 (5.5) 3-metoxi-PCP 1 −18.0 86.4 101 (6.1) BZP 1 22.1 44.2 98.6 (6.7) Diethylpropion 0.1 −11.3 96.2 99.0 (6.7) DMT 0.1 −7.3 76.5 93.7 (2.6) DOB 1 18.5 82.5 87.8 (4.9) 2-MAPB 1 4.9 86.4 99.4 (4.2) 5-MAPB 0.05 7.0 81.7 96.7 (5.6) Ketamine 0.1 −15.8 86.4 99.4 (5.5) Norketamine 1 −3.0 87.3 91.9 (6.0) Etizolam 1 −8.3 79.2 93.2 (3.9) TFMPP 0.1 10.1 91.0 94.9 (5.3) OH-LSD 1 7.7 7.2 99.0 (5.8) 5-MeO-MiPT 0.05 2.7 88.6 97.4 (4.1) mCPP 1 8.5 82.5 69.9 (7.9) Fenproporex 1 −7.2 88.4 97.3 (4.8) Mescaline 5 −6.3 10.1 99.3 (6.8) THC 1 −17.6 63.4 89.7 (12.5) Methylphenidate 0.05 −6.2 83.6 99.3 (6.3) Ephedrine 1 −17.5 45.6 98.2 (6.0) Group . Analyte . LOD (ng/mL) . Matrix effect (%) (n = 10) . Recovery (%) . Extraction (n = 10) . Quantisal™ (n = 5) (%RSD) . Fentanyl analogues Acetyl fentanyl 0.05 −7.7 103 96.0 (8.5) Acetyl norfentanyl 5 13.4 8.2 94.3 (9.7) Acrylfentanyl 0.05 −14.5 97.0 87.7 (6.8) Alfentanil 0.1 11.0 113 95.7 (6.7) Carfentanil 0.05 −5.9 110 88.5 (7.2) Fentanyl 0.05 −15.9 100 90.9 (7.0) Furanylfentanyl 0.05 −13.7 102 84.3 (7.8) Norfentanyl 1 −16.1 25.4 89.1 (8.8) Remifentanil 0.1 −17.6 114 74.7 (8.4) Sufentanil 0.1 −0.7 100 86.9 (9.1) Thiofentanyl 0.05 −3.6 103 94.6 (7.1) Valerylfentanyl 0.05 −8.8 102 63.0 (7.1) Synthetic cannabinoids AB-FUBINACA 0.1 14.1 82.9 109 (11.3) AB-PINACA 0.05 10.8 80.3 100 (13.8) APINACA 0.05 −31.3 61.4 120 (9.6) AM2201 0.05 −19.6 72.3 106 (10.1) AM2233 1 34.3 81.0 86.2 (10.4) HU-211 1 25.9 78.1 103 (10.0) JWH-015 0.05 −40.0 76.5 96.4 (12.1) JWH-019 0.05 −29.6 62.6 122 (9.5) JWH-073 0.05 −23.5 70.2 109 (10.1) JWH-081 0.05 −15.1 66.3 110 (9.0) JWH-122 0.05 −40.2 61.9 113 (9.4) JWH-175 0.05 −43.1 58.7 124 (12.1) JWH-200 0.05 10.4 79.0 96.8 (13.1) JWH-203 1 −17.4 68.9 103 (9.3) JWH-210 0.05 −37.1 64.0 126 (6.1) JWH-250 1 −18.0 71.4 98.7 (9.7) RCS-4 0.05 −22.4 70.0 99.2 (11.2) RCS-8 0.05 −29.2 64.7 117 (9.1) XLR11 0.1 −14.7 68.8 90.4 (10.6) JWH-176 1 0.8 60.4 127 (9.0) PB22 0.05 −55.5 76.8 90.0 (12.3) MMB-FUBINACA 0.05 −15.5 73.2 87.2 (1.9) Synthetic cathinones Cathinone 1 −9.1 64.5 91.5 (3.6) Methcathinone 1 −10.1 76.1 92.8 (1.2) Butylone 0.05 0.9 81.3 94.9 (3.3) Pentylone 0.05 16.9 85.5 92.7 (3.9) N-ethylpentylone 0.05 −0.2 83.8 93.8 (2.0) Mephedrone 0.05 2.9 80.3 93.7 (2.6) Methedrone 1 −11.8 75.9 92.8 (2.1) Pentedrone 1 −12.3 83.0 93.6 (1.8) Benzedrone 0.05 −8.7 83.2 88.5 (3.3) 4-Chloroethcathinone 0.05 15.6 82.9 91.8 (2.8) Dipentylone 0.1 −0.3 84.2 92.3 (3.8) Dimethylone 1 −8.2 83.7 93.4 (2.9) MDPV 0.05 10.3 83.3 95.0 (1.8) Ethylone 0.05 0.4 81.8 93.0 (1.5) Methylone 0.05 13.0 77.1 92.9 (2.6) Alpha-PVP 0.05 6.9 84.5 91.6 (3.0) Pyrovalerone 0.05 10.4 84.7 93.6 (3.3) Naphyrone 0.05 0.3 82.0 88.0 (4.7) 4-Fluoromethcathinone 1 8.4 80.2 92.2 (2.6) Phenethylamines 25B-NBOH 0.1 −6.0 79.4 79.1 (4.8) 25B-NBOMe 0.1 −16.1 71.6 70.9 (3.8) 25C-NBOH 0.1 −15.6 82.0 83.4 (5.5) 25C-NBOMe 0.05 −12.4 74.3 77.1 (5.1) 25D-NBOMe 0.1 −16.6 70.5 84.1 (4.9) 25E-NBOH 0.05 10.3 75.5 82.9 (10.7) 25E-NBOMe 0.1 −4.8 70.2 69.2 (7.2) 25G-NBOMe 0.1 −9.3 70.6 69.2 (6.6) 25H-NBOMe 0.05 −0.7 84.8 91.8 (5.4) 25I-NBOH 0.05 19.0 77.8 73.1 (7.0) 25I-NBOMe 0.05 29.0 71.3 56.7 (6.5) 25N-NBOMe 0.05 20.1 84.2 89.0 (4.6) 25T2-NBOMe 0.05 −0.6 78.6 78.0 (5.9) 2C-B 1 23.0 82.8 90.8 (10.1) 2C-C 1 6.0 78.2 72.4 (7.8) 2C-D 0.1 −13.1 66.2 90.2 (7.2) 2C-E 1 −17.0 78.9 89.2 (7.9) 2C-G 1 3.3 78.7 86.2 (8.7) 2C-I 0.1 −18.2 82.6 84.5 (7.4) 2C-T 1 −14.6 47.4 91.8 (9.8) 2C-T-2 1 7.5 63.2 85.6 (8.9) 2C-T-4 0.1 −18.4 71.6 90.7 (8.7) Other NPS and drugs of abuse LSD 0.05 −14.1 86.8 87.3 (4.5) Amphetamine 1 6.6 65.3 97.8 (5.0) Methamphetamine 1 6.8 74.0 97.2 (6.3) MDA 1 −1.5 67.7 99.9 (4.4) MDMA 1 −3.7 74.7 97.8 (4.7) MDEA 1 −3.4 83.6 97.9 (6.2) PMA 1 −11.4 60.2 97.5 (6.2) 4-MTA 1 −17.1 90.0 95.1 (5.4) DOET 1 −15.5 81.1 96.3 (5.7) DOM 1 2.4 78.1 93.3 (5.5) 3-metoxi-PCP 1 −18.0 86.4 101 (6.1) BZP 1 22.1 44.2 98.6 (6.7) Diethylpropion 0.1 −11.3 96.2 99.0 (6.7) DMT 0.1 −7.3 76.5 93.7 (2.6) DOB 1 18.5 82.5 87.8 (4.9) 2-MAPB 1 4.9 86.4 99.4 (4.2) 5-MAPB 0.05 7.0 81.7 96.7 (5.6) Ketamine 0.1 −15.8 86.4 99.4 (5.5) Norketamine 1 −3.0 87.3 91.9 (6.0) Etizolam 1 −8.3 79.2 93.2 (3.9) TFMPP 0.1 10.1 91.0 94.9 (5.3) OH-LSD 1 7.7 7.2 99.0 (5.8) 5-MeO-MiPT 0.05 2.7 88.6 97.4 (4.1) mCPP 1 8.5 82.5 69.9 (7.9) Fenproporex 1 −7.2 88.4 97.3 (4.8) Mescaline 5 −6.3 10.1 99.3 (6.8) THC 1 −17.6 63.4 89.7 (12.5) Methylphenidate 0.05 −6.2 83.6 99.3 (6.3) Ephedrine 1 −17.5 45.6 98.2 (6.0) Open in new tab Table I Limits of Detection, Matrix Effects and Recoveries of 104 New Psychoactive Substances and Other Drugs of Abuse in Oral Fluid Samples by LC–MS-MS Group . Analyte . LOD (ng/mL) . Matrix effect (%) (n = 10) . Recovery (%) . Extraction (n = 10) . Quantisal™ (n = 5) (%RSD) . Fentanyl analogues Acetyl fentanyl 0.05 −7.7 103 96.0 (8.5) Acetyl norfentanyl 5 13.4 8.2 94.3 (9.7) Acrylfentanyl 0.05 −14.5 97.0 87.7 (6.8) Alfentanil 0.1 11.0 113 95.7 (6.7) Carfentanil 0.05 −5.9 110 88.5 (7.2) Fentanyl 0.05 −15.9 100 90.9 (7.0) Furanylfentanyl 0.05 −13.7 102 84.3 (7.8) Norfentanyl 1 −16.1 25.4 89.1 (8.8) Remifentanil 0.1 −17.6 114 74.7 (8.4) Sufentanil 0.1 −0.7 100 86.9 (9.1) Thiofentanyl 0.05 −3.6 103 94.6 (7.1) Valerylfentanyl 0.05 −8.8 102 63.0 (7.1) Synthetic cannabinoids AB-FUBINACA 0.1 14.1 82.9 109 (11.3) AB-PINACA 0.05 10.8 80.3 100 (13.8) APINACA 0.05 −31.3 61.4 120 (9.6) AM2201 0.05 −19.6 72.3 106 (10.1) AM2233 1 34.3 81.0 86.2 (10.4) HU-211 1 25.9 78.1 103 (10.0) JWH-015 0.05 −40.0 76.5 96.4 (12.1) JWH-019 0.05 −29.6 62.6 122 (9.5) JWH-073 0.05 −23.5 70.2 109 (10.1) JWH-081 0.05 −15.1 66.3 110 (9.0) JWH-122 0.05 −40.2 61.9 113 (9.4) JWH-175 0.05 −43.1 58.7 124 (12.1) JWH-200 0.05 10.4 79.0 96.8 (13.1) JWH-203 1 −17.4 68.9 103 (9.3) JWH-210 0.05 −37.1 64.0 126 (6.1) JWH-250 1 −18.0 71.4 98.7 (9.7) RCS-4 0.05 −22.4 70.0 99.2 (11.2) RCS-8 0.05 −29.2 64.7 117 (9.1) XLR11 0.1 −14.7 68.8 90.4 (10.6) JWH-176 1 0.8 60.4 127 (9.0) PB22 0.05 −55.5 76.8 90.0 (12.3) MMB-FUBINACA 0.05 −15.5 73.2 87.2 (1.9) Synthetic cathinones Cathinone 1 −9.1 64.5 91.5 (3.6) Methcathinone 1 −10.1 76.1 92.8 (1.2) Butylone 0.05 0.9 81.3 94.9 (3.3) Pentylone 0.05 16.9 85.5 92.7 (3.9) N-ethylpentylone 0.05 −0.2 83.8 93.8 (2.0) Mephedrone 0.05 2.9 80.3 93.7 (2.6) Methedrone 1 −11.8 75.9 92.8 (2.1) Pentedrone 1 −12.3 83.0 93.6 (1.8) Benzedrone 0.05 −8.7 83.2 88.5 (3.3) 4-Chloroethcathinone 0.05 15.6 82.9 91.8 (2.8) Dipentylone 0.1 −0.3 84.2 92.3 (3.8) Dimethylone 1 −8.2 83.7 93.4 (2.9) MDPV 0.05 10.3 83.3 95.0 (1.8) Ethylone 0.05 0.4 81.8 93.0 (1.5) Methylone 0.05 13.0 77.1 92.9 (2.6) Alpha-PVP 0.05 6.9 84.5 91.6 (3.0) Pyrovalerone 0.05 10.4 84.7 93.6 (3.3) Naphyrone 0.05 0.3 82.0 88.0 (4.7) 4-Fluoromethcathinone 1 8.4 80.2 92.2 (2.6) Phenethylamines 25B-NBOH 0.1 −6.0 79.4 79.1 (4.8) 25B-NBOMe 0.1 −16.1 71.6 70.9 (3.8) 25C-NBOH 0.1 −15.6 82.0 83.4 (5.5) 25C-NBOMe 0.05 −12.4 74.3 77.1 (5.1) 25D-NBOMe 0.1 −16.6 70.5 84.1 (4.9) 25E-NBOH 0.05 10.3 75.5 82.9 (10.7) 25E-NBOMe 0.1 −4.8 70.2 69.2 (7.2) 25G-NBOMe 0.1 −9.3 70.6 69.2 (6.6) 25H-NBOMe 0.05 −0.7 84.8 91.8 (5.4) 25I-NBOH 0.05 19.0 77.8 73.1 (7.0) 25I-NBOMe 0.05 29.0 71.3 56.7 (6.5) 25N-NBOMe 0.05 20.1 84.2 89.0 (4.6) 25T2-NBOMe 0.05 −0.6 78.6 78.0 (5.9) 2C-B 1 23.0 82.8 90.8 (10.1) 2C-C 1 6.0 78.2 72.4 (7.8) 2C-D 0.1 −13.1 66.2 90.2 (7.2) 2C-E 1 −17.0 78.9 89.2 (7.9) 2C-G 1 3.3 78.7 86.2 (8.7) 2C-I 0.1 −18.2 82.6 84.5 (7.4) 2C-T 1 −14.6 47.4 91.8 (9.8) 2C-T-2 1 7.5 63.2 85.6 (8.9) 2C-T-4 0.1 −18.4 71.6 90.7 (8.7) Other NPS and drugs of abuse LSD 0.05 −14.1 86.8 87.3 (4.5) Amphetamine 1 6.6 65.3 97.8 (5.0) Methamphetamine 1 6.8 74.0 97.2 (6.3) MDA 1 −1.5 67.7 99.9 (4.4) MDMA 1 −3.7 74.7 97.8 (4.7) MDEA 1 −3.4 83.6 97.9 (6.2) PMA 1 −11.4 60.2 97.5 (6.2) 4-MTA 1 −17.1 90.0 95.1 (5.4) DOET 1 −15.5 81.1 96.3 (5.7) DOM 1 2.4 78.1 93.3 (5.5) 3-metoxi-PCP 1 −18.0 86.4 101 (6.1) BZP 1 22.1 44.2 98.6 (6.7) Diethylpropion 0.1 −11.3 96.2 99.0 (6.7) DMT 0.1 −7.3 76.5 93.7 (2.6) DOB 1 18.5 82.5 87.8 (4.9) 2-MAPB 1 4.9 86.4 99.4 (4.2) 5-MAPB 0.05 7.0 81.7 96.7 (5.6) Ketamine 0.1 −15.8 86.4 99.4 (5.5) Norketamine 1 −3.0 87.3 91.9 (6.0) Etizolam 1 −8.3 79.2 93.2 (3.9) TFMPP 0.1 10.1 91.0 94.9 (5.3) OH-LSD 1 7.7 7.2 99.0 (5.8) 5-MeO-MiPT 0.05 2.7 88.6 97.4 (4.1) mCPP 1 8.5 82.5 69.9 (7.9) Fenproporex 1 −7.2 88.4 97.3 (4.8) Mescaline 5 −6.3 10.1 99.3 (6.8) THC 1 −17.6 63.4 89.7 (12.5) Methylphenidate 0.05 −6.2 83.6 99.3 (6.3) Ephedrine 1 −17.5 45.6 98.2 (6.0) Group . Analyte . LOD (ng/mL) . Matrix effect (%) (n = 10) . Recovery (%) . Extraction (n = 10) . Quantisal™ (n = 5) (%RSD) . Fentanyl analogues Acetyl fentanyl 0.05 −7.7 103 96.0 (8.5) Acetyl norfentanyl 5 13.4 8.2 94.3 (9.7) Acrylfentanyl 0.05 −14.5 97.0 87.7 (6.8) Alfentanil 0.1 11.0 113 95.7 (6.7) Carfentanil 0.05 −5.9 110 88.5 (7.2) Fentanyl 0.05 −15.9 100 90.9 (7.0) Furanylfentanyl 0.05 −13.7 102 84.3 (7.8) Norfentanyl 1 −16.1 25.4 89.1 (8.8) Remifentanil 0.1 −17.6 114 74.7 (8.4) Sufentanil 0.1 −0.7 100 86.9 (9.1) Thiofentanyl 0.05 −3.6 103 94.6 (7.1) Valerylfentanyl 0.05 −8.8 102 63.0 (7.1) Synthetic cannabinoids AB-FUBINACA 0.1 14.1 82.9 109 (11.3) AB-PINACA 0.05 10.8 80.3 100 (13.8) APINACA 0.05 −31.3 61.4 120 (9.6) AM2201 0.05 −19.6 72.3 106 (10.1) AM2233 1 34.3 81.0 86.2 (10.4) HU-211 1 25.9 78.1 103 (10.0) JWH-015 0.05 −40.0 76.5 96.4 (12.1) JWH-019 0.05 −29.6 62.6 122 (9.5) JWH-073 0.05 −23.5 70.2 109 (10.1) JWH-081 0.05 −15.1 66.3 110 (9.0) JWH-122 0.05 −40.2 61.9 113 (9.4) JWH-175 0.05 −43.1 58.7 124 (12.1) JWH-200 0.05 10.4 79.0 96.8 (13.1) JWH-203 1 −17.4 68.9 103 (9.3) JWH-210 0.05 −37.1 64.0 126 (6.1) JWH-250 1 −18.0 71.4 98.7 (9.7) RCS-4 0.05 −22.4 70.0 99.2 (11.2) RCS-8 0.05 −29.2 64.7 117 (9.1) XLR11 0.1 −14.7 68.8 90.4 (10.6) JWH-176 1 0.8 60.4 127 (9.0) PB22 0.05 −55.5 76.8 90.0 (12.3) MMB-FUBINACA 0.05 −15.5 73.2 87.2 (1.9) Synthetic cathinones Cathinone 1 −9.1 64.5 91.5 (3.6) Methcathinone 1 −10.1 76.1 92.8 (1.2) Butylone 0.05 0.9 81.3 94.9 (3.3) Pentylone 0.05 16.9 85.5 92.7 (3.9) N-ethylpentylone 0.05 −0.2 83.8 93.8 (2.0) Mephedrone 0.05 2.9 80.3 93.7 (2.6) Methedrone 1 −11.8 75.9 92.8 (2.1) Pentedrone 1 −12.3 83.0 93.6 (1.8) Benzedrone 0.05 −8.7 83.2 88.5 (3.3) 4-Chloroethcathinone 0.05 15.6 82.9 91.8 (2.8) Dipentylone 0.1 −0.3 84.2 92.3 (3.8) Dimethylone 1 −8.2 83.7 93.4 (2.9) MDPV 0.05 10.3 83.3 95.0 (1.8) Ethylone 0.05 0.4 81.8 93.0 (1.5) Methylone 0.05 13.0 77.1 92.9 (2.6) Alpha-PVP 0.05 6.9 84.5 91.6 (3.0) Pyrovalerone 0.05 10.4 84.7 93.6 (3.3) Naphyrone 0.05 0.3 82.0 88.0 (4.7) 4-Fluoromethcathinone 1 8.4 80.2 92.2 (2.6) Phenethylamines 25B-NBOH 0.1 −6.0 79.4 79.1 (4.8) 25B-NBOMe 0.1 −16.1 71.6 70.9 (3.8) 25C-NBOH 0.1 −15.6 82.0 83.4 (5.5) 25C-NBOMe 0.05 −12.4 74.3 77.1 (5.1) 25D-NBOMe 0.1 −16.6 70.5 84.1 (4.9) 25E-NBOH 0.05 10.3 75.5 82.9 (10.7) 25E-NBOMe 0.1 −4.8 70.2 69.2 (7.2) 25G-NBOMe 0.1 −9.3 70.6 69.2 (6.6) 25H-NBOMe 0.05 −0.7 84.8 91.8 (5.4) 25I-NBOH 0.05 19.0 77.8 73.1 (7.0) 25I-NBOMe 0.05 29.0 71.3 56.7 (6.5) 25N-NBOMe 0.05 20.1 84.2 89.0 (4.6) 25T2-NBOMe 0.05 −0.6 78.6 78.0 (5.9) 2C-B 1 23.0 82.8 90.8 (10.1) 2C-C 1 6.0 78.2 72.4 (7.8) 2C-D 0.1 −13.1 66.2 90.2 (7.2) 2C-E 1 −17.0 78.9 89.2 (7.9) 2C-G 1 3.3 78.7 86.2 (8.7) 2C-I 0.1 −18.2 82.6 84.5 (7.4) 2C-T 1 −14.6 47.4 91.8 (9.8) 2C-T-2 1 7.5 63.2 85.6 (8.9) 2C-T-4 0.1 −18.4 71.6 90.7 (8.7) Other NPS and drugs of abuse LSD 0.05 −14.1 86.8 87.3 (4.5) Amphetamine 1 6.6 65.3 97.8 (5.0) Methamphetamine 1 6.8 74.0 97.2 (6.3) MDA 1 −1.5 67.7 99.9 (4.4) MDMA 1 −3.7 74.7 97.8 (4.7) MDEA 1 −3.4 83.6 97.9 (6.2) PMA 1 −11.4 60.2 97.5 (6.2) 4-MTA 1 −17.1 90.0 95.1 (5.4) DOET 1 −15.5 81.1 96.3 (5.7) DOM 1 2.4 78.1 93.3 (5.5) 3-metoxi-PCP 1 −18.0 86.4 101 (6.1) BZP 1 22.1 44.2 98.6 (6.7) Diethylpropion 0.1 −11.3 96.2 99.0 (6.7) DMT 0.1 −7.3 76.5 93.7 (2.6) DOB 1 18.5 82.5 87.8 (4.9) 2-MAPB 1 4.9 86.4 99.4 (4.2) 5-MAPB 0.05 7.0 81.7 96.7 (5.6) Ketamine 0.1 −15.8 86.4 99.4 (5.5) Norketamine 1 −3.0 87.3 91.9 (6.0) Etizolam 1 −8.3 79.2 93.2 (3.9) TFMPP 0.1 10.1 91.0 94.9 (5.3) OH-LSD 1 7.7 7.2 99.0 (5.8) 5-MeO-MiPT 0.05 2.7 88.6 97.4 (4.1) mCPP 1 8.5 82.5 69.9 (7.9) Fenproporex 1 −7.2 88.4 97.3 (4.8) Mescaline 5 −6.3 10.1 99.3 (6.8) THC 1 −17.6 63.4 89.7 (12.5) Methylphenidate 0.05 −6.2 83.6 99.3 (6.3) Ephedrine 1 −17.5 45.6 98.2 (6.0) Open in new tab No carryover was observed in blank oral fluid samples analyzed after high concentration samples, and no exogenous interferences were noted in those samples fortified with common pharmaceuticals. No endogenous interferences were found with different sources of oral fluid matrix. Matrix effects were less than ±20% for most analytes. In the synthetic cathinone group, matrix effects were −12–7%; for the synthetic cannabinoid group, −55–34%; −18–20% for phenethylamines; −18–13% for fentanyl analogues; and −18–22% for other NPS and common drugs of abuse. Detailed information for each analyte is found in Table I. de Castro et al. obtained an extraction recovery higher than 88%, coupled to 80% Quantisal™ device recovery for some synthetic cathinones (20). Quintela et al. also showed recovery results higher than 81.3% for some traditional drugs of abuse and metabolites at three concentrations with the Quantisal™ device. Compared to other oral fluid devices, methamphetamine had a recovery lower than 59%, but at least 93.1% recovery from the collection pad with the Quantisal™ device (25). In our experiment, similar Quantisal™ device recovery for synthetic cathinones was observed. Results were between 88.0% for naphyrone and 95.0% for MDPV. Fentanyl analogues’ recoveries were 63.0% for valerylfentanyl and 96.0% for acetyl fentanyl. The synthetic cannabinoids displayed variations from 86.2% for AM2233 to 127% for JWH-210. Phenethylamines’ recoveries were 56.7% for 25I-NBOMe and 91.8% for 25H-NBOMe and 2C-T. Other NPS recoveries were 69.9% for mCPP and 101% for 3-methoxy-PCP. The %RSD was below 13.8% for all analytes, documenting that the Quantisal™ device showed good reproducibility for oral fluid absorption and desorption (Table I). Regarding extraction recovery results, all synthetic cathinones had an extraction recovery >64%, >61% for synthetic cannabinoids, >47% for phenethylamines, >97% for fentanyl analogues and >44% for other NPS and common drugs of abuse (Table I). Synthetic cathinones usually have poor stability in other matrices (26–28); therefore, the Quantisal™ device was selected for improved stability compared to neat oral fluid and other commercial oral fluid devices. Miller et al. (29) showed that at room temperature for 1 month, synthetic cathinone concentrations decreased below detectability in neat samples and −71.2% with the Quantisal™ device. In our study, methcathinone and benzedrone decreased 20.3 and 22.9%, respectively, after 60 days at 4°C. Synthetic cannabinoids exhibited the greatest diversity in stability. MMB-FUBINACA decreased the most (−56.5%) at 4°C for 15 days. Two cannabinoids had poor stability at 4 and −20°C for 15 days: JWH-175 (−27.0 and −26.3%, respectively) and JWH-176 (−36.1 and −33.8%, respectively). APINACA had similar decreases, but only at 60 days (−31.5 and −25.7%). For the fentanyl analogues, remifentanil and metabolites norfentanyl and acetyl norfentanyl displayed the greatest decreases. At 15 days, remifentanil decreased −67.4% at 4°C, acetyl norfentanyl −20.4% at −20°C at 60 days and norfentanyl −25.8% at 60 days. 25I-NBOMe was the only phenethylamine to decrease more than 20% at 4°C at 60 days (−22.7%). These stability results indicate that authentic sample analyses should occur as soon as possible after collection, and if stored, preferably at −20°C or lower. The stability data are found in Table II. Table II Stabilities (%difference from Baseline) of 104 New Psychoactive Substances and Other Drugs of Abuse in Oral Fluid Samples Collected with Quantisal™ Device Group . Analyte . Stability (%) (%RSD, n = 3) . . . 25°C . 4°C . −20°C . . . 15 days . 15 days . 60 days . 15 days . 60 days . 90 days . Fentanyl analogues Acetyl fentanyl 10.2 (5.4) 9.1 (1.1) −11.3 (3.4) 7.8 (1.5) −14.3 (0.8) −14.4 (1.1) Acetyl norfentanyl −16.7 (6.1) −20.5 (2.5) −35.0 (1.3) −20.4 (0.6) −33.3 (6.6) −41.6 (2.5) Acrylfentanyl −11.4 (5.2) −3.5 (0.8) −22.0 (1.5) 0.8 (3.8) −12.9 (1.9) −11.8 (1.4) Alfentanil −2.1 (5.4) −4.0 (1.3) −6.3 (3.4) −4.5 (3.9) −11.3 (1.5) −21.4 (2.0) Carfentanil 6.4 (6.1) 4.0 (2.1) −4.1 (2.0) 4.7 (2.0) −9.1 (1.9) −12.0 (1.4) Fentanyl 1.6 (6.6) 1.4 (1.6) −9.1 (3.5) 1.4 (3.4) −10.4 (1.3) 5.2 (1.9) Furanylfentanyl 6.4 (5.5) 5.0 (1.4) −5.2 (3.6) 6.5 (3.9) −7.9 (3.2) −8.0 (1.1) Norfentanyl −7.8 (6.6) −13.7 (2.9) −23.0 (3.5) −12.4 (1.5) −25.8 (2.0) −34.7 (2.5) Remifentanil −100 −67.4 (1.5) −98.9 (11.5) 0.4 (1.6) −18.4 (1.1) −11.7 (3.3) Sufentanil 8.4 (5.5) 7.9 (2.9) −13.7 (3.5) 10.2 (1.7) −17.3 (0.4) −13.3 (2.7) Thiofentanyl 11.5 (5.6) 10.5 (1.9) −13.6 (0.1) 11.3 (2.2) −16.1 (0.1) −12.9 (0.7) Valerylfentanyl 5.8 (4.2) 4.9 (3.0) −15.6 (1.6) 8.1 (3.8) −15.2 (2.6) −18.7 (1.7) Synthetic cannabinoids AB-FUBINACA 10.4 (3.1) 8.7 (10.2) 18.2 (2.9) 16.3 (6.7) 29.0 (3.6) 85.1 (12.0) AB-PINACA 20.0 (1.5) 16.3 (9.5) 15.6 (5.7) 25.1 (5.9) 32.8 (4.6) 8.0 (8.8) APINACA −16.4 (6.8) 4.7 (6.2) −31.5 (8.8) −9.2 (1.6) −25.7 (0.1) −28.9 (5.6) AM2201 1.3 (3.7) 4.8 (9.5) 18.4 (1.4) 2.5 (5.8) 26.4 (4.2) −2.1 (7.1) AM2233 17.2 (3.0) 11.9 (12.0) −2.4 (3.1) 22.6 (4.9) 8.2 (5.9) 9.5 (12.9) HU-211 13.9 (3.0) 13.4 (12.2) 1.6 (3.4) −21.6 (6.2) 12.1 (1.8) 19.5 (9.2) JWH-015 −2.4 (9.3) 8.4 (8.5) −1.1 (3.0) 10.9 (4.9) 9.4 (8.2) −59.6 (11.4) JWH-019 4.9 (4.1) 15.2 (8.6) −8.3 (4.3) 7.5 (4.0) −2.0 (1.9) −9.9 (9.3) JWH-073 −2.3 (4.6) 10.5 (9.2) −2.1 (2.5) 2.9 (4.8) −1.0 (3.7) −23.4 (1.4) JWH-081 20.1 (4.8) 19.2 (8.9) 0.6 (3.7) 14.7 (6.6) 11.0 (1.3) 8.9 (12.8) JWH-122 −11.2 (4.6) −3.7 (9.8) −21.2 (3.0) −4.2 (9.1) −8.7 (3.7) 6.2 (11.1) JWH-175 −68.1 (15.5) −27.0 (3.7) −64.8 (14.9) −26.3 (5.7) −48.1 (5.4) −65.2 (7.4) JWH-200 13.7 (2.1) 15.9 (10.0) 16.7 (1.6) 22.9 (3.3) 25.2 (6.3) 24.2 (5.1) JWH-203 −24.8 (5.5) −1.8 (8.0) −8.9 (3.1) −0.3 (5.2) 2.3 (1.9) −22.0 (5.3) JWH-210 1.5 (3.4) 5.3 (9.2) −39.2 (7.2) 7.3 (5.6) −23.7 (1.4) −15.7 (8.6) JWH-250 −19.2 (3.5) −7.0 (9.9) −5.5 (4.2) −4.8 (5.7) 8.9 (1.1) −17.4 (7.5) RCS-4 −16.1 (5.8) 1.2 (9.5) 6.8 (1.3) 5.9 (6.6) 21.6 (3.7) −1.7 (3.7) RCS-8 5.0 (3.9) 11.6 (8.9) −21.3 (5.9) 0.3 (4.5) −16.4 (3.3) −14.7 (9.2) XLR11 −36.7 (5.8) −18.4 (9.4) −29.5 (3.3) −4.6 (6.5) 2.1 (2.9) −5.5 (5.8) JWH-176 −70.9 (15.1) −36.1 (6.1) −71.3 (16.0) −33.8 (2.9) −59.2 (5.5) −73.1 (4.4) PB22 −17.3 (6.9) 1.8 (9.5) 0.1 (2.0) 6.0 (5.7) 14.0 (8.6) −46.8 (2.7) MMB-FUBINACA −95.6 (31.7) −56.5 (10.6) −89.5 (2.2) 7.5 (7.2) 22.4 (1.9) 4.2 (8.7) Synthetic cathinones Cathinone −49.2 (1.4) −0.8 (3.1) −10.2 (1.2) 0.6 (3.5) −10.1 (1.6) −25.1 (0.4) Methcathinone −57.7 (2.9) −2.9 (2.4) −20.3 (2.1) −1.3 (2.6) 3.6 (4.0) −11.7 (4.0) Butylone 1.8 (1.5) 8.9 (1.7) −1.4 (2.0) 6.7 (1.9) 4.5 (1.2) −9.2 (0.6) Pentylone −4.7 (2.3) 6.1 (1.0) −0.6 (0.8) 3.8 (1.9) 0.3 (5.2) 2.2 (2.2) N-ethylpentylone 1.9 (0.4) 8.4 (1.2) 7.1 (1.2) 6.2 (2.6) 12.1 (2.1) 5.8 (1.1) Mephedrone −14.8 (2.4) 14.9 (2.2) 0.1 (2.9) 12.0 (0.6) 13.3 (0.6) −9.6 (0.6) Methedrone −7.1 (0.9) 6.7 (2.5) −8.9 (1.7) 1.3 (0.7) −2.4 (2.1) −6.8 (1.9) Pentedrone −18.8 (2.2) 6.9 (2.3) −4.1 (3.3) 5.7 (2.8) 4.4 (1.1) −2.9 (3.1) Benzedrone −75.9 (6.9) −9.7 (3.5) −22.9 (3.1) −4.7 (4.1) 19.6 (1.3) 6.0 (2.0) 4-Chloroethcathinone −74.8 (10.1) −9.9 (1.6) −19.7 (0.2) −4.5 (4.6) 10.5 (3.1) 0.0 (0.8) Dipentylone −1.4 (0.7) 3.8 (1.6) 15.0 (3.0) −0.7 (2.5) 18.2 (2.5) 7.3 (2.7) Dimethylone −0.3 (0.9) 3.2 (3.0) 0.9 (1.6) −1.1 (0.7) 2.6 (0.3) 2.3 (2.6) MDPV −4.2 (2.4) −1.9 (1.9) 16.1 (1.6) −3.0 (3.5) 18.5 (2.9) 6.4 (1.1) Ethylone 1.1 (1.7) 8.1 (1.0) 6.4 (2.5) 5.2 (2.6) 11.3 (0.6) −5.4 (1.3) Methylone −11.8 (2.4) 3.5 (2.4) 3.4 (1.8) 1.6 (1.2) 9.3 (0.9) −3.0 (1.6) Alpha-PVP 0.9 (2.4) 5.2 (4.4) 12.7 (2.3) 3.7 (2.6) 18.5 (1.3) 8.7 (1.3) Pyrovalerone −0.9 (1.3) 3.7 (3.3) 14.0 (3.1) 1.1 (3.3) 17.5 (2.9) 9.9 (2.5) Naphyrone −0.9 (4.2) 6.6 (0.5) 17.8 (2.3) 4.0 (2.4) 21.3 (3.4) 9.9 (1.9) 4-Fluoromethcathinone −53.4 (5.0) −0.9 (2.2) −11.7 (2.3) 2.5 (2.4) 10.7 (1.7) −5.8 (2.5) Phenethylamines 25B-NBOH 2.7 (3.6) 11.9 (2.2) −7.7 (3.5) 8.5 (0.5) 1.1 (1.6) −6.5 (3.2) 25B-NBOMe −24.3 (3.0) −9.6 (2.5) −18.4 (0.8) −2.7 (1.5) 3.0 (6.5) 9.7 (1.8) 25C-NBOH 9.0 (2.7) 16.6 (0.9) −6.4 (0.6) 13.9 (1.9) 0.4 (3.7) −1.8 (3.0) 25C-NBOMe −10.3 (4.4) −0.2 (1.6) −15.1 (1.0) 5.4 (0.6) 2.8 (3.1) 0.5 (3.4) 25D-NBOMe −24.8 (4.8) −13.0 (3.1) −15.7 (1.9) −5.4 (0.6) 10.3 (2.4) 10.5 (4.2) 25E-NBOH 5.1 (6.3) 15.6 (7.5) 11.0 (11.6) 11.4 (4.9) 5.0 (18.1) 0.0 (9.4) 25E-NBOMe −7.5 (2.7) 3.7 (1.1) −13.8 (1.9) 11.3 (1.6) 6.8 (3.5) 0.9 (3.3) 25G-NBOMe −5.2 (4.1) 6.6 (1.1) −15.5 (2.3) 14.5 (2.0) 4.4 (4.0) 6.4 (3.3) 25H-NBOMe −2.2 (4.7) 1.7 (2.4) −7.8 (1.5) −2.1 (2.1) −3.7 (1.8) −0.5 (3.0) 25I-NBOH 1.0 (3.1) 9.1 (2.9) −3.7 (1.6) 6.7 (3.0) 3.9 (3.1) 9.8 (3.1) 25I-NBOMe −22.0 (4.5) −4.2 (3.3) −22.7 (0.9) 11.4 (1.2) 7.6 (3.4) −2.6 (3.8) 25N-NBOMe −1.5 (3.6) 4.9 (0.2) −4.2 (0.7) 5.2 (2.8) 4.2 (3.0) −1.9 (4.1) 25T2-NBOMe −20.5 (4.6) −8.4 (5.0) −19.4 (1.5) 3.7 (1.4) 6.8 (2.1) −2.1 (4.0) 2C-B 0.2 (4.6) 3.3 (3.7) 8.2 (3.9) 3.9 (4.1) 9.6 (1.9) −1.1 (6.0) 2C-C −11.2 (4.3) −9.4 (2.2) −12.4 (1.0) −7.4 (2.0) −10.6 (2.8) −6.1 (5.3) 2C-D −3.9 (1.1) −0.5 (3.1) −14.8 (0.5) −2.2 (2.1) −14.1 (2.4) −9.2 (6.8) 2C-E −2.5 (4.0) −0.8 (1.5) −13.8 (1.5) −3.0 (2.8) −13.7 (2.7) −3.9 (4.6) 2C-G −6.2 (2.8) −7.2 (1.0) −12.6 (1.0) −6.4 (2.4) −11.8 (3.0) −10.1 (2.4) 2C-I 3.5 (4.2) 3.4 (3.5) −2.1 (2.4) 3.2 (2.8) −0.1 (2.5) 13.2 (5.9) 2C-T −11.8 (1.5) −11.2 (1.3) −15.7 (2.5) −6.4 (0.8) −11.3 (2.2) −15.3 (3.7) 2C-T-2 −2.3 (2.8) −4.3 (1.0) −5.1 (2.9) −3.0 (3.3) 1.0 (2.9) −10.5 (4.4) 2C-T-4 9.9 (2.7) 8.7 (0.7) −4.3 (0.3) 10.7 (3.5) −1.1 (2.1) −3.8 (3.4) Other NPS and drugs of abuse LSD −14.3 (2.8) −5.2 (1.8) −10.7 (1.9) −4.3 (1.9) −0.4 (4.3) −0.2 (2.8) Amphetamine −4.3 (2.6) −0.7 (2.0) 6.8 (2.4) −1.7 (0.8) 11.6 (2.8) −26.0 (1.4) Methamphetamine −1.6 (2.3) −0.2 (2.3) 1.4 (3.1) −1.2 (1.0) 4.9 (3.3) −4.5 (1.0) MDA −3.3 (3.0) 0.5 (2.2) 4.8 (3.0) −3.8 (0.7) 9.6 (4.6) −12.1 (1.0) MDMA 2.3 (7.2) 0.0 (4.1) 1.2 (3.2) −0.9 (2.5) 1.7 (3.2) −2.2 (1.4) MDEA −0.6 (3.2) 0.8 (3.2) 1.3 (3.1) −2.3 (0.6) 3.6 (2.5) −4.1 (1.1) PMA −3.3 (2.2) −0.1 (2.3) −1.0 (3.1) −3.8 (0.6) 0.6 (2.8) −19.4 (1.6) 4-MTA −19.9 (1.0) −3.0 (4.4) 3.7 (2.1) −0.9 (1.3) 8.9 (4.0) −4.5 (1.6) DOET 7.4 (3.2) 9.9 (1.7) 5.4 (3.4) 8.4 (2.2) 9.6 (2.6) −3.3 (2.5) DOM −6.7 (2.1) −6.2 (4.7) −0.4 (1.8) −8.0 (2.4) 3.0 (4.0) 12.8 (1.0) 3-Metoxi-PCP 9.9 (3.5) 7.3 (2.9) 9.5 (3.8) 7.5 (2.7) 13.5 (4.2) 9.5 (2.0) BZP 10.1 (1.2) 14.0 (2.8) 20.2 (1.5) 13.9 (0.9) 28.6 (3.3) 19.0 (2.0) Diethylpropion −1.7 (0.9) −1.9 (2.3) 9.8 (3.6) −2.0 (0.9) 17.3 (1.6) 16.6 (2.4) DMT −53.3 (4.9) 3.1 (1.8) −18.1 (6.2) 6.1 (3.1) 11.1 (3.6) −0.9 (5.5) DOB 7.2 (0.2) 6.9 (1.7) 8.1 (5.2) 4.0 (0.6) 8.7 (4.3) 14.2 (5.5) 2-MAPB −0.5 (3.2) 2.0 (2.1) 11.3 (3.4) 1.0 (0.7) 14.4 (4.3) −1.3 (1.9) 5-MAPB 5.6 (2.1) 7.8 (2.8) 9.5 (4.0) 5.7 (1.2) 11.9 (2.8) 10.1 (1.6) Ketamine 19.7 (4.3) 19.7 (0.8) 19.8 (1.7) 18.1 (1.1) 25.3 (4.7) 12.9 (1.9) Norketamine 6.6 (2.7) 12.0 (4.6) 12.1 (4.9) 6.9 (1.2) 17.6 (1.8) 1.5 (1.5) Etizolam −3.1 (2.6) −7.6 (1.3) 7.1 (3.8) 0.9 (2.7) 23.9 (0.6) 17.4 (12.3) TFMPP 5.9 (2.2) 8.7 (3.7) 11.5 (2.0) 8.5 (0.9) 13.9 (2.5) −0.7 (2.0) OH-LSD −36.7 (5.9) −17.3 (1.5) −18.0 (4.5) −17.4 (11.9) 0.9 (7.8) −14.4 (3.8) 5-MeO-MiPT −6.6 (2.0) −3.6 (5.2) 9.9 (5.0) −3.3 (0.7) 13.3 (2.7) 9.7 (0.7) mCPP −3.0 (7.3) 1.1 (3.0) −3.8 (5.2) 2.2 (1.5) −2.7 (2.8) −7.4 (15.5) Fenproporex 10.1 (2.7) 13.1 (3.4) 12.3 (1.4) 13.4 (1.1) 16.1 (2.6) −11.4 (0.5) Mescaline −10.5 (13.4) −1.7 (1.6) −10.2 (4.2) −15.2 (8.1) −0.3 (11.2) −16.8 (7.9) THC 1.0 (1.1) 16.0 (0.9) −3.9 (4.0) 9.1 (1.6) −3.0 (6.1) 7.7 (1.1) Methylphenidate −44.8 (4.0) 6.7 (2.8) −12.8 (3.7) 12.6 (1.0) 12.8 (2.8) 6.8 (0.9) Ephedrine 0.4 (1.7) 0.9 (2.8) 1.4 (3.5) 1.2 (1.3) 6.9 (1.8) −25.9 (2.7) Group . Analyte . Stability (%) (%RSD, n = 3) . . . 25°C . 4°C . −20°C . . . 15 days . 15 days . 60 days . 15 days . 60 days . 90 days . Fentanyl analogues Acetyl fentanyl 10.2 (5.4) 9.1 (1.1) −11.3 (3.4) 7.8 (1.5) −14.3 (0.8) −14.4 (1.1) Acetyl norfentanyl −16.7 (6.1) −20.5 (2.5) −35.0 (1.3) −20.4 (0.6) −33.3 (6.6) −41.6 (2.5) Acrylfentanyl −11.4 (5.2) −3.5 (0.8) −22.0 (1.5) 0.8 (3.8) −12.9 (1.9) −11.8 (1.4) Alfentanil −2.1 (5.4) −4.0 (1.3) −6.3 (3.4) −4.5 (3.9) −11.3 (1.5) −21.4 (2.0) Carfentanil 6.4 (6.1) 4.0 (2.1) −4.1 (2.0) 4.7 (2.0) −9.1 (1.9) −12.0 (1.4) Fentanyl 1.6 (6.6) 1.4 (1.6) −9.1 (3.5) 1.4 (3.4) −10.4 (1.3) 5.2 (1.9) Furanylfentanyl 6.4 (5.5) 5.0 (1.4) −5.2 (3.6) 6.5 (3.9) −7.9 (3.2) −8.0 (1.1) Norfentanyl −7.8 (6.6) −13.7 (2.9) −23.0 (3.5) −12.4 (1.5) −25.8 (2.0) −34.7 (2.5) Remifentanil −100 −67.4 (1.5) −98.9 (11.5) 0.4 (1.6) −18.4 (1.1) −11.7 (3.3) Sufentanil 8.4 (5.5) 7.9 (2.9) −13.7 (3.5) 10.2 (1.7) −17.3 (0.4) −13.3 (2.7) Thiofentanyl 11.5 (5.6) 10.5 (1.9) −13.6 (0.1) 11.3 (2.2) −16.1 (0.1) −12.9 (0.7) Valerylfentanyl 5.8 (4.2) 4.9 (3.0) −15.6 (1.6) 8.1 (3.8) −15.2 (2.6) −18.7 (1.7) Synthetic cannabinoids AB-FUBINACA 10.4 (3.1) 8.7 (10.2) 18.2 (2.9) 16.3 (6.7) 29.0 (3.6) 85.1 (12.0) AB-PINACA 20.0 (1.5) 16.3 (9.5) 15.6 (5.7) 25.1 (5.9) 32.8 (4.6) 8.0 (8.8) APINACA −16.4 (6.8) 4.7 (6.2) −31.5 (8.8) −9.2 (1.6) −25.7 (0.1) −28.9 (5.6) AM2201 1.3 (3.7) 4.8 (9.5) 18.4 (1.4) 2.5 (5.8) 26.4 (4.2) −2.1 (7.1) AM2233 17.2 (3.0) 11.9 (12.0) −2.4 (3.1) 22.6 (4.9) 8.2 (5.9) 9.5 (12.9) HU-211 13.9 (3.0) 13.4 (12.2) 1.6 (3.4) −21.6 (6.2) 12.1 (1.8) 19.5 (9.2) JWH-015 −2.4 (9.3) 8.4 (8.5) −1.1 (3.0) 10.9 (4.9) 9.4 (8.2) −59.6 (11.4) JWH-019 4.9 (4.1) 15.2 (8.6) −8.3 (4.3) 7.5 (4.0) −2.0 (1.9) −9.9 (9.3) JWH-073 −2.3 (4.6) 10.5 (9.2) −2.1 (2.5) 2.9 (4.8) −1.0 (3.7) −23.4 (1.4) JWH-081 20.1 (4.8) 19.2 (8.9) 0.6 (3.7) 14.7 (6.6) 11.0 (1.3) 8.9 (12.8) JWH-122 −11.2 (4.6) −3.7 (9.8) −21.2 (3.0) −4.2 (9.1) −8.7 (3.7) 6.2 (11.1) JWH-175 −68.1 (15.5) −27.0 (3.7) −64.8 (14.9) −26.3 (5.7) −48.1 (5.4) −65.2 (7.4) JWH-200 13.7 (2.1) 15.9 (10.0) 16.7 (1.6) 22.9 (3.3) 25.2 (6.3) 24.2 (5.1) JWH-203 −24.8 (5.5) −1.8 (8.0) −8.9 (3.1) −0.3 (5.2) 2.3 (1.9) −22.0 (5.3) JWH-210 1.5 (3.4) 5.3 (9.2) −39.2 (7.2) 7.3 (5.6) −23.7 (1.4) −15.7 (8.6) JWH-250 −19.2 (3.5) −7.0 (9.9) −5.5 (4.2) −4.8 (5.7) 8.9 (1.1) −17.4 (7.5) RCS-4 −16.1 (5.8) 1.2 (9.5) 6.8 (1.3) 5.9 (6.6) 21.6 (3.7) −1.7 (3.7) RCS-8 5.0 (3.9) 11.6 (8.9) −21.3 (5.9) 0.3 (4.5) −16.4 (3.3) −14.7 (9.2) XLR11 −36.7 (5.8) −18.4 (9.4) −29.5 (3.3) −4.6 (6.5) 2.1 (2.9) −5.5 (5.8) JWH-176 −70.9 (15.1) −36.1 (6.1) −71.3 (16.0) −33.8 (2.9) −59.2 (5.5) −73.1 (4.4) PB22 −17.3 (6.9) 1.8 (9.5) 0.1 (2.0) 6.0 (5.7) 14.0 (8.6) −46.8 (2.7) MMB-FUBINACA −95.6 (31.7) −56.5 (10.6) −89.5 (2.2) 7.5 (7.2) 22.4 (1.9) 4.2 (8.7) Synthetic cathinones Cathinone −49.2 (1.4) −0.8 (3.1) −10.2 (1.2) 0.6 (3.5) −10.1 (1.6) −25.1 (0.4) Methcathinone −57.7 (2.9) −2.9 (2.4) −20.3 (2.1) −1.3 (2.6) 3.6 (4.0) −11.7 (4.0) Butylone 1.8 (1.5) 8.9 (1.7) −1.4 (2.0) 6.7 (1.9) 4.5 (1.2) −9.2 (0.6) Pentylone −4.7 (2.3) 6.1 (1.0) −0.6 (0.8) 3.8 (1.9) 0.3 (5.2) 2.2 (2.2) N-ethylpentylone 1.9 (0.4) 8.4 (1.2) 7.1 (1.2) 6.2 (2.6) 12.1 (2.1) 5.8 (1.1) Mephedrone −14.8 (2.4) 14.9 (2.2) 0.1 (2.9) 12.0 (0.6) 13.3 (0.6) −9.6 (0.6) Methedrone −7.1 (0.9) 6.7 (2.5) −8.9 (1.7) 1.3 (0.7) −2.4 (2.1) −6.8 (1.9) Pentedrone −18.8 (2.2) 6.9 (2.3) −4.1 (3.3) 5.7 (2.8) 4.4 (1.1) −2.9 (3.1) Benzedrone −75.9 (6.9) −9.7 (3.5) −22.9 (3.1) −4.7 (4.1) 19.6 (1.3) 6.0 (2.0) 4-Chloroethcathinone −74.8 (10.1) −9.9 (1.6) −19.7 (0.2) −4.5 (4.6) 10.5 (3.1) 0.0 (0.8) Dipentylone −1.4 (0.7) 3.8 (1.6) 15.0 (3.0) −0.7 (2.5) 18.2 (2.5) 7.3 (2.7) Dimethylone −0.3 (0.9) 3.2 (3.0) 0.9 (1.6) −1.1 (0.7) 2.6 (0.3) 2.3 (2.6) MDPV −4.2 (2.4) −1.9 (1.9) 16.1 (1.6) −3.0 (3.5) 18.5 (2.9) 6.4 (1.1) Ethylone 1.1 (1.7) 8.1 (1.0) 6.4 (2.5) 5.2 (2.6) 11.3 (0.6) −5.4 (1.3) Methylone −11.8 (2.4) 3.5 (2.4) 3.4 (1.8) 1.6 (1.2) 9.3 (0.9) −3.0 (1.6) Alpha-PVP 0.9 (2.4) 5.2 (4.4) 12.7 (2.3) 3.7 (2.6) 18.5 (1.3) 8.7 (1.3) Pyrovalerone −0.9 (1.3) 3.7 (3.3) 14.0 (3.1) 1.1 (3.3) 17.5 (2.9) 9.9 (2.5) Naphyrone −0.9 (4.2) 6.6 (0.5) 17.8 (2.3) 4.0 (2.4) 21.3 (3.4) 9.9 (1.9) 4-Fluoromethcathinone −53.4 (5.0) −0.9 (2.2) −11.7 (2.3) 2.5 (2.4) 10.7 (1.7) −5.8 (2.5) Phenethylamines 25B-NBOH 2.7 (3.6) 11.9 (2.2) −7.7 (3.5) 8.5 (0.5) 1.1 (1.6) −6.5 (3.2) 25B-NBOMe −24.3 (3.0) −9.6 (2.5) −18.4 (0.8) −2.7 (1.5) 3.0 (6.5) 9.7 (1.8) 25C-NBOH 9.0 (2.7) 16.6 (0.9) −6.4 (0.6) 13.9 (1.9) 0.4 (3.7) −1.8 (3.0) 25C-NBOMe −10.3 (4.4) −0.2 (1.6) −15.1 (1.0) 5.4 (0.6) 2.8 (3.1) 0.5 (3.4) 25D-NBOMe −24.8 (4.8) −13.0 (3.1) −15.7 (1.9) −5.4 (0.6) 10.3 (2.4) 10.5 (4.2) 25E-NBOH 5.1 (6.3) 15.6 (7.5) 11.0 (11.6) 11.4 (4.9) 5.0 (18.1) 0.0 (9.4) 25E-NBOMe −7.5 (2.7) 3.7 (1.1) −13.8 (1.9) 11.3 (1.6) 6.8 (3.5) 0.9 (3.3) 25G-NBOMe −5.2 (4.1) 6.6 (1.1) −15.5 (2.3) 14.5 (2.0) 4.4 (4.0) 6.4 (3.3) 25H-NBOMe −2.2 (4.7) 1.7 (2.4) −7.8 (1.5) −2.1 (2.1) −3.7 (1.8) −0.5 (3.0) 25I-NBOH 1.0 (3.1) 9.1 (2.9) −3.7 (1.6) 6.7 (3.0) 3.9 (3.1) 9.8 (3.1) 25I-NBOMe −22.0 (4.5) −4.2 (3.3) −22.7 (0.9) 11.4 (1.2) 7.6 (3.4) −2.6 (3.8) 25N-NBOMe −1.5 (3.6) 4.9 (0.2) −4.2 (0.7) 5.2 (2.8) 4.2 (3.0) −1.9 (4.1) 25T2-NBOMe −20.5 (4.6) −8.4 (5.0) −19.4 (1.5) 3.7 (1.4) 6.8 (2.1) −2.1 (4.0) 2C-B 0.2 (4.6) 3.3 (3.7) 8.2 (3.9) 3.9 (4.1) 9.6 (1.9) −1.1 (6.0) 2C-C −11.2 (4.3) −9.4 (2.2) −12.4 (1.0) −7.4 (2.0) −10.6 (2.8) −6.1 (5.3) 2C-D −3.9 (1.1) −0.5 (3.1) −14.8 (0.5) −2.2 (2.1) −14.1 (2.4) −9.2 (6.8) 2C-E −2.5 (4.0) −0.8 (1.5) −13.8 (1.5) −3.0 (2.8) −13.7 (2.7) −3.9 (4.6) 2C-G −6.2 (2.8) −7.2 (1.0) −12.6 (1.0) −6.4 (2.4) −11.8 (3.0) −10.1 (2.4) 2C-I 3.5 (4.2) 3.4 (3.5) −2.1 (2.4) 3.2 (2.8) −0.1 (2.5) 13.2 (5.9) 2C-T −11.8 (1.5) −11.2 (1.3) −15.7 (2.5) −6.4 (0.8) −11.3 (2.2) −15.3 (3.7) 2C-T-2 −2.3 (2.8) −4.3 (1.0) −5.1 (2.9) −3.0 (3.3) 1.0 (2.9) −10.5 (4.4) 2C-T-4 9.9 (2.7) 8.7 (0.7) −4.3 (0.3) 10.7 (3.5) −1.1 (2.1) −3.8 (3.4) Other NPS and drugs of abuse LSD −14.3 (2.8) −5.2 (1.8) −10.7 (1.9) −4.3 (1.9) −0.4 (4.3) −0.2 (2.8) Amphetamine −4.3 (2.6) −0.7 (2.0) 6.8 (2.4) −1.7 (0.8) 11.6 (2.8) −26.0 (1.4) Methamphetamine −1.6 (2.3) −0.2 (2.3) 1.4 (3.1) −1.2 (1.0) 4.9 (3.3) −4.5 (1.0) MDA −3.3 (3.0) 0.5 (2.2) 4.8 (3.0) −3.8 (0.7) 9.6 (4.6) −12.1 (1.0) MDMA 2.3 (7.2) 0.0 (4.1) 1.2 (3.2) −0.9 (2.5) 1.7 (3.2) −2.2 (1.4) MDEA −0.6 (3.2) 0.8 (3.2) 1.3 (3.1) −2.3 (0.6) 3.6 (2.5) −4.1 (1.1) PMA −3.3 (2.2) −0.1 (2.3) −1.0 (3.1) −3.8 (0.6) 0.6 (2.8) −19.4 (1.6) 4-MTA −19.9 (1.0) −3.0 (4.4) 3.7 (2.1) −0.9 (1.3) 8.9 (4.0) −4.5 (1.6) DOET 7.4 (3.2) 9.9 (1.7) 5.4 (3.4) 8.4 (2.2) 9.6 (2.6) −3.3 (2.5) DOM −6.7 (2.1) −6.2 (4.7) −0.4 (1.8) −8.0 (2.4) 3.0 (4.0) 12.8 (1.0) 3-Metoxi-PCP 9.9 (3.5) 7.3 (2.9) 9.5 (3.8) 7.5 (2.7) 13.5 (4.2) 9.5 (2.0) BZP 10.1 (1.2) 14.0 (2.8) 20.2 (1.5) 13.9 (0.9) 28.6 (3.3) 19.0 (2.0) Diethylpropion −1.7 (0.9) −1.9 (2.3) 9.8 (3.6) −2.0 (0.9) 17.3 (1.6) 16.6 (2.4) DMT −53.3 (4.9) 3.1 (1.8) −18.1 (6.2) 6.1 (3.1) 11.1 (3.6) −0.9 (5.5) DOB 7.2 (0.2) 6.9 (1.7) 8.1 (5.2) 4.0 (0.6) 8.7 (4.3) 14.2 (5.5) 2-MAPB −0.5 (3.2) 2.0 (2.1) 11.3 (3.4) 1.0 (0.7) 14.4 (4.3) −1.3 (1.9) 5-MAPB 5.6 (2.1) 7.8 (2.8) 9.5 (4.0) 5.7 (1.2) 11.9 (2.8) 10.1 (1.6) Ketamine 19.7 (4.3) 19.7 (0.8) 19.8 (1.7) 18.1 (1.1) 25.3 (4.7) 12.9 (1.9) Norketamine 6.6 (2.7) 12.0 (4.6) 12.1 (4.9) 6.9 (1.2) 17.6 (1.8) 1.5 (1.5) Etizolam −3.1 (2.6) −7.6 (1.3) 7.1 (3.8) 0.9 (2.7) 23.9 (0.6) 17.4 (12.3) TFMPP 5.9 (2.2) 8.7 (3.7) 11.5 (2.0) 8.5 (0.9) 13.9 (2.5) −0.7 (2.0) OH-LSD −36.7 (5.9) −17.3 (1.5) −18.0 (4.5) −17.4 (11.9) 0.9 (7.8) −14.4 (3.8) 5-MeO-MiPT −6.6 (2.0) −3.6 (5.2) 9.9 (5.0) −3.3 (0.7) 13.3 (2.7) 9.7 (0.7) mCPP −3.0 (7.3) 1.1 (3.0) −3.8 (5.2) 2.2 (1.5) −2.7 (2.8) −7.4 (15.5) Fenproporex 10.1 (2.7) 13.1 (3.4) 12.3 (1.4) 13.4 (1.1) 16.1 (2.6) −11.4 (0.5) Mescaline −10.5 (13.4) −1.7 (1.6) −10.2 (4.2) −15.2 (8.1) −0.3 (11.2) −16.8 (7.9) THC 1.0 (1.1) 16.0 (0.9) −3.9 (4.0) 9.1 (1.6) −3.0 (6.1) 7.7 (1.1) Methylphenidate −44.8 (4.0) 6.7 (2.8) −12.8 (3.7) 12.6 (1.0) 12.8 (2.8) 6.8 (0.9) Ephedrine 0.4 (1.7) 0.9 (2.8) 1.4 (3.5) 1.2 (1.3) 6.9 (1.8) −25.9 (2.7) Open in new tab Table II Stabilities (%difference from Baseline) of 104 New Psychoactive Substances and Other Drugs of Abuse in Oral Fluid Samples Collected with Quantisal™ Device Group . Analyte . Stability (%) (%RSD, n = 3) . . . 25°C . 4°C . −20°C . . . 15 days . 15 days . 60 days . 15 days . 60 days . 90 days . Fentanyl analogues Acetyl fentanyl 10.2 (5.4) 9.1 (1.1) −11.3 (3.4) 7.8 (1.5) −14.3 (0.8) −14.4 (1.1) Acetyl norfentanyl −16.7 (6.1) −20.5 (2.5) −35.0 (1.3) −20.4 (0.6) −33.3 (6.6) −41.6 (2.5) Acrylfentanyl −11.4 (5.2) −3.5 (0.8) −22.0 (1.5) 0.8 (3.8) −12.9 (1.9) −11.8 (1.4) Alfentanil −2.1 (5.4) −4.0 (1.3) −6.3 (3.4) −4.5 (3.9) −11.3 (1.5) −21.4 (2.0) Carfentanil 6.4 (6.1) 4.0 (2.1) −4.1 (2.0) 4.7 (2.0) −9.1 (1.9) −12.0 (1.4) Fentanyl 1.6 (6.6) 1.4 (1.6) −9.1 (3.5) 1.4 (3.4) −10.4 (1.3) 5.2 (1.9) Furanylfentanyl 6.4 (5.5) 5.0 (1.4) −5.2 (3.6) 6.5 (3.9) −7.9 (3.2) −8.0 (1.1) Norfentanyl −7.8 (6.6) −13.7 (2.9) −23.0 (3.5) −12.4 (1.5) −25.8 (2.0) −34.7 (2.5) Remifentanil −100 −67.4 (1.5) −98.9 (11.5) 0.4 (1.6) −18.4 (1.1) −11.7 (3.3) Sufentanil 8.4 (5.5) 7.9 (2.9) −13.7 (3.5) 10.2 (1.7) −17.3 (0.4) −13.3 (2.7) Thiofentanyl 11.5 (5.6) 10.5 (1.9) −13.6 (0.1) 11.3 (2.2) −16.1 (0.1) −12.9 (0.7) Valerylfentanyl 5.8 (4.2) 4.9 (3.0) −15.6 (1.6) 8.1 (3.8) −15.2 (2.6) −18.7 (1.7) Synthetic cannabinoids AB-FUBINACA 10.4 (3.1) 8.7 (10.2) 18.2 (2.9) 16.3 (6.7) 29.0 (3.6) 85.1 (12.0) AB-PINACA 20.0 (1.5) 16.3 (9.5) 15.6 (5.7) 25.1 (5.9) 32.8 (4.6) 8.0 (8.8) APINACA −16.4 (6.8) 4.7 (6.2) −31.5 (8.8) −9.2 (1.6) −25.7 (0.1) −28.9 (5.6) AM2201 1.3 (3.7) 4.8 (9.5) 18.4 (1.4) 2.5 (5.8) 26.4 (4.2) −2.1 (7.1) AM2233 17.2 (3.0) 11.9 (12.0) −2.4 (3.1) 22.6 (4.9) 8.2 (5.9) 9.5 (12.9) HU-211 13.9 (3.0) 13.4 (12.2) 1.6 (3.4) −21.6 (6.2) 12.1 (1.8) 19.5 (9.2) JWH-015 −2.4 (9.3) 8.4 (8.5) −1.1 (3.0) 10.9 (4.9) 9.4 (8.2) −59.6 (11.4) JWH-019 4.9 (4.1) 15.2 (8.6) −8.3 (4.3) 7.5 (4.0) −2.0 (1.9) −9.9 (9.3) JWH-073 −2.3 (4.6) 10.5 (9.2) −2.1 (2.5) 2.9 (4.8) −1.0 (3.7) −23.4 (1.4) JWH-081 20.1 (4.8) 19.2 (8.9) 0.6 (3.7) 14.7 (6.6) 11.0 (1.3) 8.9 (12.8) JWH-122 −11.2 (4.6) −3.7 (9.8) −21.2 (3.0) −4.2 (9.1) −8.7 (3.7) 6.2 (11.1) JWH-175 −68.1 (15.5) −27.0 (3.7) −64.8 (14.9) −26.3 (5.7) −48.1 (5.4) −65.2 (7.4) JWH-200 13.7 (2.1) 15.9 (10.0) 16.7 (1.6) 22.9 (3.3) 25.2 (6.3) 24.2 (5.1) JWH-203 −24.8 (5.5) −1.8 (8.0) −8.9 (3.1) −0.3 (5.2) 2.3 (1.9) −22.0 (5.3) JWH-210 1.5 (3.4) 5.3 (9.2) −39.2 (7.2) 7.3 (5.6) −23.7 (1.4) −15.7 (8.6) JWH-250 −19.2 (3.5) −7.0 (9.9) −5.5 (4.2) −4.8 (5.7) 8.9 (1.1) −17.4 (7.5) RCS-4 −16.1 (5.8) 1.2 (9.5) 6.8 (1.3) 5.9 (6.6) 21.6 (3.7) −1.7 (3.7) RCS-8 5.0 (3.9) 11.6 (8.9) −21.3 (5.9) 0.3 (4.5) −16.4 (3.3) −14.7 (9.2) XLR11 −36.7 (5.8) −18.4 (9.4) −29.5 (3.3) −4.6 (6.5) 2.1 (2.9) −5.5 (5.8) JWH-176 −70.9 (15.1) −36.1 (6.1) −71.3 (16.0) −33.8 (2.9) −59.2 (5.5) −73.1 (4.4) PB22 −17.3 (6.9) 1.8 (9.5) 0.1 (2.0) 6.0 (5.7) 14.0 (8.6) −46.8 (2.7) MMB-FUBINACA −95.6 (31.7) −56.5 (10.6) −89.5 (2.2) 7.5 (7.2) 22.4 (1.9) 4.2 (8.7) Synthetic cathinones Cathinone −49.2 (1.4) −0.8 (3.1) −10.2 (1.2) 0.6 (3.5) −10.1 (1.6) −25.1 (0.4) Methcathinone −57.7 (2.9) −2.9 (2.4) −20.3 (2.1) −1.3 (2.6) 3.6 (4.0) −11.7 (4.0) Butylone 1.8 (1.5) 8.9 (1.7) −1.4 (2.0) 6.7 (1.9) 4.5 (1.2) −9.2 (0.6) Pentylone −4.7 (2.3) 6.1 (1.0) −0.6 (0.8) 3.8 (1.9) 0.3 (5.2) 2.2 (2.2) N-ethylpentylone 1.9 (0.4) 8.4 (1.2) 7.1 (1.2) 6.2 (2.6) 12.1 (2.1) 5.8 (1.1) Mephedrone −14.8 (2.4) 14.9 (2.2) 0.1 (2.9) 12.0 (0.6) 13.3 (0.6) −9.6 (0.6) Methedrone −7.1 (0.9) 6.7 (2.5) −8.9 (1.7) 1.3 (0.7) −2.4 (2.1) −6.8 (1.9) Pentedrone −18.8 (2.2) 6.9 (2.3) −4.1 (3.3) 5.7 (2.8) 4.4 (1.1) −2.9 (3.1) Benzedrone −75.9 (6.9) −9.7 (3.5) −22.9 (3.1) −4.7 (4.1) 19.6 (1.3) 6.0 (2.0) 4-Chloroethcathinone −74.8 (10.1) −9.9 (1.6) −19.7 (0.2) −4.5 (4.6) 10.5 (3.1) 0.0 (0.8) Dipentylone −1.4 (0.7) 3.8 (1.6) 15.0 (3.0) −0.7 (2.5) 18.2 (2.5) 7.3 (2.7) Dimethylone −0.3 (0.9) 3.2 (3.0) 0.9 (1.6) −1.1 (0.7) 2.6 (0.3) 2.3 (2.6) MDPV −4.2 (2.4) −1.9 (1.9) 16.1 (1.6) −3.0 (3.5) 18.5 (2.9) 6.4 (1.1) Ethylone 1.1 (1.7) 8.1 (1.0) 6.4 (2.5) 5.2 (2.6) 11.3 (0.6) −5.4 (1.3) Methylone −11.8 (2.4) 3.5 (2.4) 3.4 (1.8) 1.6 (1.2) 9.3 (0.9) −3.0 (1.6) Alpha-PVP 0.9 (2.4) 5.2 (4.4) 12.7 (2.3) 3.7 (2.6) 18.5 (1.3) 8.7 (1.3) Pyrovalerone −0.9 (1.3) 3.7 (3.3) 14.0 (3.1) 1.1 (3.3) 17.5 (2.9) 9.9 (2.5) Naphyrone −0.9 (4.2) 6.6 (0.5) 17.8 (2.3) 4.0 (2.4) 21.3 (3.4) 9.9 (1.9) 4-Fluoromethcathinone −53.4 (5.0) −0.9 (2.2) −11.7 (2.3) 2.5 (2.4) 10.7 (1.7) −5.8 (2.5) Phenethylamines 25B-NBOH 2.7 (3.6) 11.9 (2.2) −7.7 (3.5) 8.5 (0.5) 1.1 (1.6) −6.5 (3.2) 25B-NBOMe −24.3 (3.0) −9.6 (2.5) −18.4 (0.8) −2.7 (1.5) 3.0 (6.5) 9.7 (1.8) 25C-NBOH 9.0 (2.7) 16.6 (0.9) −6.4 (0.6) 13.9 (1.9) 0.4 (3.7) −1.8 (3.0) 25C-NBOMe −10.3 (4.4) −0.2 (1.6) −15.1 (1.0) 5.4 (0.6) 2.8 (3.1) 0.5 (3.4) 25D-NBOMe −24.8 (4.8) −13.0 (3.1) −15.7 (1.9) −5.4 (0.6) 10.3 (2.4) 10.5 (4.2) 25E-NBOH 5.1 (6.3) 15.6 (7.5) 11.0 (11.6) 11.4 (4.9) 5.0 (18.1) 0.0 (9.4) 25E-NBOMe −7.5 (2.7) 3.7 (1.1) −13.8 (1.9) 11.3 (1.6) 6.8 (3.5) 0.9 (3.3) 25G-NBOMe −5.2 (4.1) 6.6 (1.1) −15.5 (2.3) 14.5 (2.0) 4.4 (4.0) 6.4 (3.3) 25H-NBOMe −2.2 (4.7) 1.7 (2.4) −7.8 (1.5) −2.1 (2.1) −3.7 (1.8) −0.5 (3.0) 25I-NBOH 1.0 (3.1) 9.1 (2.9) −3.7 (1.6) 6.7 (3.0) 3.9 (3.1) 9.8 (3.1) 25I-NBOMe −22.0 (4.5) −4.2 (3.3) −22.7 (0.9) 11.4 (1.2) 7.6 (3.4) −2.6 (3.8) 25N-NBOMe −1.5 (3.6) 4.9 (0.2) −4.2 (0.7) 5.2 (2.8) 4.2 (3.0) −1.9 (4.1) 25T2-NBOMe −20.5 (4.6) −8.4 (5.0) −19.4 (1.5) 3.7 (1.4) 6.8 (2.1) −2.1 (4.0) 2C-B 0.2 (4.6) 3.3 (3.7) 8.2 (3.9) 3.9 (4.1) 9.6 (1.9) −1.1 (6.0) 2C-C −11.2 (4.3) −9.4 (2.2) −12.4 (1.0) −7.4 (2.0) −10.6 (2.8) −6.1 (5.3) 2C-D −3.9 (1.1) −0.5 (3.1) −14.8 (0.5) −2.2 (2.1) −14.1 (2.4) −9.2 (6.8) 2C-E −2.5 (4.0) −0.8 (1.5) −13.8 (1.5) −3.0 (2.8) −13.7 (2.7) −3.9 (4.6) 2C-G −6.2 (2.8) −7.2 (1.0) −12.6 (1.0) −6.4 (2.4) −11.8 (3.0) −10.1 (2.4) 2C-I 3.5 (4.2) 3.4 (3.5) −2.1 (2.4) 3.2 (2.8) −0.1 (2.5) 13.2 (5.9) 2C-T −11.8 (1.5) −11.2 (1.3) −15.7 (2.5) −6.4 (0.8) −11.3 (2.2) −15.3 (3.7) 2C-T-2 −2.3 (2.8) −4.3 (1.0) −5.1 (2.9) −3.0 (3.3) 1.0 (2.9) −10.5 (4.4) 2C-T-4 9.9 (2.7) 8.7 (0.7) −4.3 (0.3) 10.7 (3.5) −1.1 (2.1) −3.8 (3.4) Other NPS and drugs of abuse LSD −14.3 (2.8) −5.2 (1.8) −10.7 (1.9) −4.3 (1.9) −0.4 (4.3) −0.2 (2.8) Amphetamine −4.3 (2.6) −0.7 (2.0) 6.8 (2.4) −1.7 (0.8) 11.6 (2.8) −26.0 (1.4) Methamphetamine −1.6 (2.3) −0.2 (2.3) 1.4 (3.1) −1.2 (1.0) 4.9 (3.3) −4.5 (1.0) MDA −3.3 (3.0) 0.5 (2.2) 4.8 (3.0) −3.8 (0.7) 9.6 (4.6) −12.1 (1.0) MDMA 2.3 (7.2) 0.0 (4.1) 1.2 (3.2) −0.9 (2.5) 1.7 (3.2) −2.2 (1.4) MDEA −0.6 (3.2) 0.8 (3.2) 1.3 (3.1) −2.3 (0.6) 3.6 (2.5) −4.1 (1.1) PMA −3.3 (2.2) −0.1 (2.3) −1.0 (3.1) −3.8 (0.6) 0.6 (2.8) −19.4 (1.6) 4-MTA −19.9 (1.0) −3.0 (4.4) 3.7 (2.1) −0.9 (1.3) 8.9 (4.0) −4.5 (1.6) DOET 7.4 (3.2) 9.9 (1.7) 5.4 (3.4) 8.4 (2.2) 9.6 (2.6) −3.3 (2.5) DOM −6.7 (2.1) −6.2 (4.7) −0.4 (1.8) −8.0 (2.4) 3.0 (4.0) 12.8 (1.0) 3-Metoxi-PCP 9.9 (3.5) 7.3 (2.9) 9.5 (3.8) 7.5 (2.7) 13.5 (4.2) 9.5 (2.0) BZP 10.1 (1.2) 14.0 (2.8) 20.2 (1.5) 13.9 (0.9) 28.6 (3.3) 19.0 (2.0) Diethylpropion −1.7 (0.9) −1.9 (2.3) 9.8 (3.6) −2.0 (0.9) 17.3 (1.6) 16.6 (2.4) DMT −53.3 (4.9) 3.1 (1.8) −18.1 (6.2) 6.1 (3.1) 11.1 (3.6) −0.9 (5.5) DOB 7.2 (0.2) 6.9 (1.7) 8.1 (5.2) 4.0 (0.6) 8.7 (4.3) 14.2 (5.5) 2-MAPB −0.5 (3.2) 2.0 (2.1) 11.3 (3.4) 1.0 (0.7) 14.4 (4.3) −1.3 (1.9) 5-MAPB 5.6 (2.1) 7.8 (2.8) 9.5 (4.0) 5.7 (1.2) 11.9 (2.8) 10.1 (1.6) Ketamine 19.7 (4.3) 19.7 (0.8) 19.8 (1.7) 18.1 (1.1) 25.3 (4.7) 12.9 (1.9) Norketamine 6.6 (2.7) 12.0 (4.6) 12.1 (4.9) 6.9 (1.2) 17.6 (1.8) 1.5 (1.5) Etizolam −3.1 (2.6) −7.6 (1.3) 7.1 (3.8) 0.9 (2.7) 23.9 (0.6) 17.4 (12.3) TFMPP 5.9 (2.2) 8.7 (3.7) 11.5 (2.0) 8.5 (0.9) 13.9 (2.5) −0.7 (2.0) OH-LSD −36.7 (5.9) −17.3 (1.5) −18.0 (4.5) −17.4 (11.9) 0.9 (7.8) −14.4 (3.8) 5-MeO-MiPT −6.6 (2.0) −3.6 (5.2) 9.9 (5.0) −3.3 (0.7) 13.3 (2.7) 9.7 (0.7) mCPP −3.0 (7.3) 1.1 (3.0) −3.8 (5.2) 2.2 (1.5) −2.7 (2.8) −7.4 (15.5) Fenproporex 10.1 (2.7) 13.1 (3.4) 12.3 (1.4) 13.4 (1.1) 16.1 (2.6) −11.4 (0.5) Mescaline −10.5 (13.4) −1.7 (1.6) −10.2 (4.2) −15.2 (8.1) −0.3 (11.2) −16.8 (7.9) THC 1.0 (1.1) 16.0 (0.9) −3.9 (4.0) 9.1 (1.6) −3.0 (6.1) 7.7 (1.1) Methylphenidate −44.8 (4.0) 6.7 (2.8) −12.8 (3.7) 12.6 (1.0) 12.8 (2.8) 6.8 (0.9) Ephedrine 0.4 (1.7) 0.9 (2.8) 1.4 (3.5) 1.2 (1.3) 6.9 (1.8) −25.9 (2.7) Group . Analyte . Stability (%) (%RSD, n = 3) . . . 25°C . 4°C . −20°C . . . 15 days . 15 days . 60 days . 15 days . 60 days . 90 days . Fentanyl analogues Acetyl fentanyl 10.2 (5.4) 9.1 (1.1) −11.3 (3.4) 7.8 (1.5) −14.3 (0.8) −14.4 (1.1) Acetyl norfentanyl −16.7 (6.1) −20.5 (2.5) −35.0 (1.3) −20.4 (0.6) −33.3 (6.6) −41.6 (2.5) Acrylfentanyl −11.4 (5.2) −3.5 (0.8) −22.0 (1.5) 0.8 (3.8) −12.9 (1.9) −11.8 (1.4) Alfentanil −2.1 (5.4) −4.0 (1.3) −6.3 (3.4) −4.5 (3.9) −11.3 (1.5) −21.4 (2.0) Carfentanil 6.4 (6.1) 4.0 (2.1) −4.1 (2.0) 4.7 (2.0) −9.1 (1.9) −12.0 (1.4) Fentanyl 1.6 (6.6) 1.4 (1.6) −9.1 (3.5) 1.4 (3.4) −10.4 (1.3) 5.2 (1.9) Furanylfentanyl 6.4 (5.5) 5.0 (1.4) −5.2 (3.6) 6.5 (3.9) −7.9 (3.2) −8.0 (1.1) Norfentanyl −7.8 (6.6) −13.7 (2.9) −23.0 (3.5) −12.4 (1.5) −25.8 (2.0) −34.7 (2.5) Remifentanil −100 −67.4 (1.5) −98.9 (11.5) 0.4 (1.6) −18.4 (1.1) −11.7 (3.3) Sufentanil 8.4 (5.5) 7.9 (2.9) −13.7 (3.5) 10.2 (1.7) −17.3 (0.4) −13.3 (2.7) Thiofentanyl 11.5 (5.6) 10.5 (1.9) −13.6 (0.1) 11.3 (2.2) −16.1 (0.1) −12.9 (0.7) Valerylfentanyl 5.8 (4.2) 4.9 (3.0) −15.6 (1.6) 8.1 (3.8) −15.2 (2.6) −18.7 (1.7) Synthetic cannabinoids AB-FUBINACA 10.4 (3.1) 8.7 (10.2) 18.2 (2.9) 16.3 (6.7) 29.0 (3.6) 85.1 (12.0) AB-PINACA 20.0 (1.5) 16.3 (9.5) 15.6 (5.7) 25.1 (5.9) 32.8 (4.6) 8.0 (8.8) APINACA −16.4 (6.8) 4.7 (6.2) −31.5 (8.8) −9.2 (1.6) −25.7 (0.1) −28.9 (5.6) AM2201 1.3 (3.7) 4.8 (9.5) 18.4 (1.4) 2.5 (5.8) 26.4 (4.2) −2.1 (7.1) AM2233 17.2 (3.0) 11.9 (12.0) −2.4 (3.1) 22.6 (4.9) 8.2 (5.9) 9.5 (12.9) HU-211 13.9 (3.0) 13.4 (12.2) 1.6 (3.4) −21.6 (6.2) 12.1 (1.8) 19.5 (9.2) JWH-015 −2.4 (9.3) 8.4 (8.5) −1.1 (3.0) 10.9 (4.9) 9.4 (8.2) −59.6 (11.4) JWH-019 4.9 (4.1) 15.2 (8.6) −8.3 (4.3) 7.5 (4.0) −2.0 (1.9) −9.9 (9.3) JWH-073 −2.3 (4.6) 10.5 (9.2) −2.1 (2.5) 2.9 (4.8) −1.0 (3.7) −23.4 (1.4) JWH-081 20.1 (4.8) 19.2 (8.9) 0.6 (3.7) 14.7 (6.6) 11.0 (1.3) 8.9 (12.8) JWH-122 −11.2 (4.6) −3.7 (9.8) −21.2 (3.0) −4.2 (9.1) −8.7 (3.7) 6.2 (11.1) JWH-175 −68.1 (15.5) −27.0 (3.7) −64.8 (14.9) −26.3 (5.7) −48.1 (5.4) −65.2 (7.4) JWH-200 13.7 (2.1) 15.9 (10.0) 16.7 (1.6) 22.9 (3.3) 25.2 (6.3) 24.2 (5.1) JWH-203 −24.8 (5.5) −1.8 (8.0) −8.9 (3.1) −0.3 (5.2) 2.3 (1.9) −22.0 (5.3) JWH-210 1.5 (3.4) 5.3 (9.2) −39.2 (7.2) 7.3 (5.6) −23.7 (1.4) −15.7 (8.6) JWH-250 −19.2 (3.5) −7.0 (9.9) −5.5 (4.2) −4.8 (5.7) 8.9 (1.1) −17.4 (7.5) RCS-4 −16.1 (5.8) 1.2 (9.5) 6.8 (1.3) 5.9 (6.6) 21.6 (3.7) −1.7 (3.7) RCS-8 5.0 (3.9) 11.6 (8.9) −21.3 (5.9) 0.3 (4.5) −16.4 (3.3) −14.7 (9.2) XLR11 −36.7 (5.8) −18.4 (9.4) −29.5 (3.3) −4.6 (6.5) 2.1 (2.9) −5.5 (5.8) JWH-176 −70.9 (15.1) −36.1 (6.1) −71.3 (16.0) −33.8 (2.9) −59.2 (5.5) −73.1 (4.4) PB22 −17.3 (6.9) 1.8 (9.5) 0.1 (2.0) 6.0 (5.7) 14.0 (8.6) −46.8 (2.7) MMB-FUBINACA −95.6 (31.7) −56.5 (10.6) −89.5 (2.2) 7.5 (7.2) 22.4 (1.9) 4.2 (8.7) Synthetic cathinones Cathinone −49.2 (1.4) −0.8 (3.1) −10.2 (1.2) 0.6 (3.5) −10.1 (1.6) −25.1 (0.4) Methcathinone −57.7 (2.9) −2.9 (2.4) −20.3 (2.1) −1.3 (2.6) 3.6 (4.0) −11.7 (4.0) Butylone 1.8 (1.5) 8.9 (1.7) −1.4 (2.0) 6.7 (1.9) 4.5 (1.2) −9.2 (0.6) Pentylone −4.7 (2.3) 6.1 (1.0) −0.6 (0.8) 3.8 (1.9) 0.3 (5.2) 2.2 (2.2) N-ethylpentylone 1.9 (0.4) 8.4 (1.2) 7.1 (1.2) 6.2 (2.6) 12.1 (2.1) 5.8 (1.1) Mephedrone −14.8 (2.4) 14.9 (2.2) 0.1 (2.9) 12.0 (0.6) 13.3 (0.6) −9.6 (0.6) Methedrone −7.1 (0.9) 6.7 (2.5) −8.9 (1.7) 1.3 (0.7) −2.4 (2.1) −6.8 (1.9) Pentedrone −18.8 (2.2) 6.9 (2.3) −4.1 (3.3) 5.7 (2.8) 4.4 (1.1) −2.9 (3.1) Benzedrone −75.9 (6.9) −9.7 (3.5) −22.9 (3.1) −4.7 (4.1) 19.6 (1.3) 6.0 (2.0) 4-Chloroethcathinone −74.8 (10.1) −9.9 (1.6) −19.7 (0.2) −4.5 (4.6) 10.5 (3.1) 0.0 (0.8) Dipentylone −1.4 (0.7) 3.8 (1.6) 15.0 (3.0) −0.7 (2.5) 18.2 (2.5) 7.3 (2.7) Dimethylone −0.3 (0.9) 3.2 (3.0) 0.9 (1.6) −1.1 (0.7) 2.6 (0.3) 2.3 (2.6) MDPV −4.2 (2.4) −1.9 (1.9) 16.1 (1.6) −3.0 (3.5) 18.5 (2.9) 6.4 (1.1) Ethylone 1.1 (1.7) 8.1 (1.0) 6.4 (2.5) 5.2 (2.6) 11.3 (0.6) −5.4 (1.3) Methylone −11.8 (2.4) 3.5 (2.4) 3.4 (1.8) 1.6 (1.2) 9.3 (0.9) −3.0 (1.6) Alpha-PVP 0.9 (2.4) 5.2 (4.4) 12.7 (2.3) 3.7 (2.6) 18.5 (1.3) 8.7 (1.3) Pyrovalerone −0.9 (1.3) 3.7 (3.3) 14.0 (3.1) 1.1 (3.3) 17.5 (2.9) 9.9 (2.5) Naphyrone −0.9 (4.2) 6.6 (0.5) 17.8 (2.3) 4.0 (2.4) 21.3 (3.4) 9.9 (1.9) 4-Fluoromethcathinone −53.4 (5.0) −0.9 (2.2) −11.7 (2.3) 2.5 (2.4) 10.7 (1.7) −5.8 (2.5) Phenethylamines 25B-NBOH 2.7 (3.6) 11.9 (2.2) −7.7 (3.5) 8.5 (0.5) 1.1 (1.6) −6.5 (3.2) 25B-NBOMe −24.3 (3.0) −9.6 (2.5) −18.4 (0.8) −2.7 (1.5) 3.0 (6.5) 9.7 (1.8) 25C-NBOH 9.0 (2.7) 16.6 (0.9) −6.4 (0.6) 13.9 (1.9) 0.4 (3.7) −1.8 (3.0) 25C-NBOMe −10.3 (4.4) −0.2 (1.6) −15.1 (1.0) 5.4 (0.6) 2.8 (3.1) 0.5 (3.4) 25D-NBOMe −24.8 (4.8) −13.0 (3.1) −15.7 (1.9) −5.4 (0.6) 10.3 (2.4) 10.5 (4.2) 25E-NBOH 5.1 (6.3) 15.6 (7.5) 11.0 (11.6) 11.4 (4.9) 5.0 (18.1) 0.0 (9.4) 25E-NBOMe −7.5 (2.7) 3.7 (1.1) −13.8 (1.9) 11.3 (1.6) 6.8 (3.5) 0.9 (3.3) 25G-NBOMe −5.2 (4.1) 6.6 (1.1) −15.5 (2.3) 14.5 (2.0) 4.4 (4.0) 6.4 (3.3) 25H-NBOMe −2.2 (4.7) 1.7 (2.4) −7.8 (1.5) −2.1 (2.1) −3.7 (1.8) −0.5 (3.0) 25I-NBOH 1.0 (3.1) 9.1 (2.9) −3.7 (1.6) 6.7 (3.0) 3.9 (3.1) 9.8 (3.1) 25I-NBOMe −22.0 (4.5) −4.2 (3.3) −22.7 (0.9) 11.4 (1.2) 7.6 (3.4) −2.6 (3.8) 25N-NBOMe −1.5 (3.6) 4.9 (0.2) −4.2 (0.7) 5.2 (2.8) 4.2 (3.0) −1.9 (4.1) 25T2-NBOMe −20.5 (4.6) −8.4 (5.0) −19.4 (1.5) 3.7 (1.4) 6.8 (2.1) −2.1 (4.0) 2C-B 0.2 (4.6) 3.3 (3.7) 8.2 (3.9) 3.9 (4.1) 9.6 (1.9) −1.1 (6.0) 2C-C −11.2 (4.3) −9.4 (2.2) −12.4 (1.0) −7.4 (2.0) −10.6 (2.8) −6.1 (5.3) 2C-D −3.9 (1.1) −0.5 (3.1) −14.8 (0.5) −2.2 (2.1) −14.1 (2.4) −9.2 (6.8) 2C-E −2.5 (4.0) −0.8 (1.5) −13.8 (1.5) −3.0 (2.8) −13.7 (2.7) −3.9 (4.6) 2C-G −6.2 (2.8) −7.2 (1.0) −12.6 (1.0) −6.4 (2.4) −11.8 (3.0) −10.1 (2.4) 2C-I 3.5 (4.2) 3.4 (3.5) −2.1 (2.4) 3.2 (2.8) −0.1 (2.5) 13.2 (5.9) 2C-T −11.8 (1.5) −11.2 (1.3) −15.7 (2.5) −6.4 (0.8) −11.3 (2.2) −15.3 (3.7) 2C-T-2 −2.3 (2.8) −4.3 (1.0) −5.1 (2.9) −3.0 (3.3) 1.0 (2.9) −10.5 (4.4) 2C-T-4 9.9 (2.7) 8.7 (0.7) −4.3 (0.3) 10.7 (3.5) −1.1 (2.1) −3.8 (3.4) Other NPS and drugs of abuse LSD −14.3 (2.8) −5.2 (1.8) −10.7 (1.9) −4.3 (1.9) −0.4 (4.3) −0.2 (2.8) Amphetamine −4.3 (2.6) −0.7 (2.0) 6.8 (2.4) −1.7 (0.8) 11.6 (2.8) −26.0 (1.4) Methamphetamine −1.6 (2.3) −0.2 (2.3) 1.4 (3.1) −1.2 (1.0) 4.9 (3.3) −4.5 (1.0) MDA −3.3 (3.0) 0.5 (2.2) 4.8 (3.0) −3.8 (0.7) 9.6 (4.6) −12.1 (1.0) MDMA 2.3 (7.2) 0.0 (4.1) 1.2 (3.2) −0.9 (2.5) 1.7 (3.2) −2.2 (1.4) MDEA −0.6 (3.2) 0.8 (3.2) 1.3 (3.1) −2.3 (0.6) 3.6 (2.5) −4.1 (1.1) PMA −3.3 (2.2) −0.1 (2.3) −1.0 (3.1) −3.8 (0.6) 0.6 (2.8) −19.4 (1.6) 4-MTA −19.9 (1.0) −3.0 (4.4) 3.7 (2.1) −0.9 (1.3) 8.9 (4.0) −4.5 (1.6) DOET 7.4 (3.2) 9.9 (1.7) 5.4 (3.4) 8.4 (2.2) 9.6 (2.6) −3.3 (2.5) DOM −6.7 (2.1) −6.2 (4.7) −0.4 (1.8) −8.0 (2.4) 3.0 (4.0) 12.8 (1.0) 3-Metoxi-PCP 9.9 (3.5) 7.3 (2.9) 9.5 (3.8) 7.5 (2.7) 13.5 (4.2) 9.5 (2.0) BZP 10.1 (1.2) 14.0 (2.8) 20.2 (1.5) 13.9 (0.9) 28.6 (3.3) 19.0 (2.0) Diethylpropion −1.7 (0.9) −1.9 (2.3) 9.8 (3.6) −2.0 (0.9) 17.3 (1.6) 16.6 (2.4) DMT −53.3 (4.9) 3.1 (1.8) −18.1 (6.2) 6.1 (3.1) 11.1 (3.6) −0.9 (5.5) DOB 7.2 (0.2) 6.9 (1.7) 8.1 (5.2) 4.0 (0.6) 8.7 (4.3) 14.2 (5.5) 2-MAPB −0.5 (3.2) 2.0 (2.1) 11.3 (3.4) 1.0 (0.7) 14.4 (4.3) −1.3 (1.9) 5-MAPB 5.6 (2.1) 7.8 (2.8) 9.5 (4.0) 5.7 (1.2) 11.9 (2.8) 10.1 (1.6) Ketamine 19.7 (4.3) 19.7 (0.8) 19.8 (1.7) 18.1 (1.1) 25.3 (4.7) 12.9 (1.9) Norketamine 6.6 (2.7) 12.0 (4.6) 12.1 (4.9) 6.9 (1.2) 17.6 (1.8) 1.5 (1.5) Etizolam −3.1 (2.6) −7.6 (1.3) 7.1 (3.8) 0.9 (2.7) 23.9 (0.6) 17.4 (12.3) TFMPP 5.9 (2.2) 8.7 (3.7) 11.5 (2.0) 8.5 (0.9) 13.9 (2.5) −0.7 (2.0) OH-LSD −36.7 (5.9) −17.3 (1.5) −18.0 (4.5) −17.4 (11.9) 0.9 (7.8) −14.4 (3.8) 5-MeO-MiPT −6.6 (2.0) −3.6 (5.2) 9.9 (5.0) −3.3 (0.7) 13.3 (2.7) 9.7 (0.7) mCPP −3.0 (7.3) 1.1 (3.0) −3.8 (5.2) 2.2 (1.5) −2.7 (2.8) −7.4 (15.5) Fenproporex 10.1 (2.7) 13.1 (3.4) 12.3 (1.4) 13.4 (1.1) 16.1 (2.6) −11.4 (0.5) Mescaline −10.5 (13.4) −1.7 (1.6) −10.2 (4.2) −15.2 (8.1) −0.3 (11.2) −16.8 (7.9) THC 1.0 (1.1) 16.0 (0.9) −3.9 (4.0) 9.1 (1.6) −3.0 (6.1) 7.7 (1.1) Methylphenidate −44.8 (4.0) 6.7 (2.8) −12.8 (3.7) 12.6 (1.0) 12.8 (2.8) 6.8 (0.9) Ephedrine 0.4 (1.7) 0.9 (2.8) 1.4 (3.5) 1.2 (1.3) 6.9 (1.8) −25.9 (2.7) Open in new tab Other available NPS oral fluid methods do not cover the variety of NPS groups or number of analytes as are achieved in the current method (maximum 39 analytes (29–35). One of the methods evaluated the Quantisal™ oral fluid collection device for synthetic cathinones and the other for cannabinoids (29, 36). According to the Brazilian Health Regulatory Agency (ANVISA), 100 NPS were identified in Brazil between 2014 and 2017. In 2017, the most abundant NPS were synthetic cathinones at 46%, followed by phenethylamines at 26%. N-ethylpentylone and 25I-NBOH were the NPS most identified from cases involving seizures (10). Other analytes identified included pentylone, alpha-PVP, ethylone, pentedrone, 25I-NBOMe, 25B-NBOMe, 25B-NBOH and 2C-I. From the synthetic cannabinoids class AB-FUBINACA, MMB-FUBINACA, JWH-081, JWH-122 and JWH-250 were reported. Furanylfentanyl was also identified in ‘LSD’ blotter paper sheets seized by the São Paulo State Police (37). Other than the report cited above, the other main information source for selecting NPS for our method took into account intoxication cases identified by poison control centers. N-ethylpentylone, butylone and fentanyl were the main NPS found in serious hospitalization cases, including fatalities (6, 38). Lastly, the international early warning systems, such as NDEWS (7), CFSRE (8) and EWS (1), also monitored the introduction of new NPS to guide our selection of drugs to incorporate into the method. In 2019, etizolam was the most commonly identified benzodiazepine by the Drug Enforcement Administration and reported to the Annual Emerging Threat Report (7). In a similar manner, TFMPP prevalence led to our inclusion of this drug in our ‘other’ category. However, acquisition of certified reference materials for NPS in Brazil remains a challenge for any laboratory. Oral fluid samples are relatively simple to collect and are adequately obtained by trained non-medical staff. Drummer demonstrated the value of oral fluid samples in diagnostic, workplace, driving under influence of drugs and pharmacokinetic purposes (39). However, the physiological effects of various psychoactive substances, such as MDMA and THC, can potentially decrease salivation, which makes it difficult to collect oral fluid (40, 41). Garg and Cooley also report potential contamination from environmental exposure and high sample collection device variability, which make it difficult to standardize oral fluid methods (15). Oral fluid samples can be obtained by passive drool and expectoration and with collection devices. Many devices are commercially available. Differences involving the sample volume collected, device recovery and stability must be evaluated when selecting a device (41). The Quantisal™ device demonstrated good performance in the parameters studied for most of these analytes. An adequate total volume sample (4 mL), 1-mL oral fluid and 3-mL elution buffer, is available for confirmatory quantitative analysis, if necessary. The absence of deuterated NPS internal standards is a limitation of the method; however, inclusion of six deuterated IS eluting across the chromatographic run proved satisfactory for accurate analysis. In addition, the carryover limit was evaluated at 10 ng/mL. We compared the chromatographic peak area of the 10-ng/mL carryover control sample with the peak area of any drug in the following sample to determine if the following sample had to be re-extracted. This is a limitation in that there could be samples following NPS-positive samples with concentrations >10 ng/mL (our carryover limit). In routine analysis utilizing this method, we add 10-ng/mL carryover controls by group for all analytes, to determine if the area of the following sample is greater than the carryover control sample to determine if the following sample needs to be reanalyzed. To demonstrate that the analytical method was fit for purpose, we analyzed seven oral fluid samples collected from volunteers present at electronic music festival with self-report use of synthetic drug in the last 24 h. Figure 2 shows the extracted ion chromatograms of seven samples that screened positive for 16 drugs included in the method. Figure 2 Open in new tabDownload slide Extracted ion chromatograms of seven authentic oral fluid samples with positive results for 17 different NPS, other drugs of abuse and metabolites. Figure 2 Open in new tabDownload slide Extracted ion chromatograms of seven authentic oral fluid samples with positive results for 17 different NPS, other drugs of abuse and metabolites. Conclusion This screening method simultaneously identifies the presence of 104 NPS and other drugs of abuse in oral fluid with good sensitivity and selectivity, following a simple liquid–liquid extraction. The method includes NPS and other drugs of abuse in a single assay, allowing a rapid screening of multiple drug classes in an efficient and economical manner. To the best of our knowledge, this is the first screening method to identify more than 100 NPS (including multiple NPS classes) and other drugs of abuse in oral fluid samples. Previously published papers were dedicated to specific NPS groups and/or fewer analytes, which requires more than one extraction or injection to cover a wide range of analytes. The large number of substances screened simultaneously in this method did not compromise the high sensitivity achieved, allowing us to detect most analytes in oral fluid with LODs as low as 0.05 or 0.1 ng/mL. The use of a simple liquid–liquid extraction procedure, covering a great number of different substances, is a less expensive alternative to solid-phase extraction. Unfortunately, our sample preparation procedure was not able to extract benzoylecgonine, cocaine’s major metabolite. The Quantisal™ device’s elution buffer stabilized all analytes at room temperature for 24 h, which is an advantage for onsite sample collection, but longer storage of the oral fluid–elution buffer mixture prior to or after LC–MS-MS analysis should be at −20°C. Also, the Quantisal™ device had good recovery for most NPS. The NBOMes and NBOHs had lower recoveries, and doses were small due to their high potencies. Finally, the authentic samples collected onsite proved that oral fluid is a good matrix to monitor NPS consumption. This oral fluid method for 104 drugs of abuse and NPS is a useful tool for identifying the type and prevalence of drugs of abuse and NPS usage in Brazil. 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TI - Screening of 104 New Psychoactive Substances (NPS) and Other Drugs of Abuse in Oral Fluid by LC–MS-MS
JF - Journal of Analytical Toxicology
DO - 10.1093/jat/bkaa089
DA - 2020-10-12
UR - https://www.deepdyve.com/lp/oxford-university-press/screening-of-104-new-psychoactive-substances-nps-and-other-drugs-of-J27bdklOPd
SP - 697
EP - 707
VL - 44
IS - 7
DP - DeepDyve
ER -