Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine

Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine

This panel is used to assess misuse of novel/new psychoactive substances (NPS).

Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine

Test Summary

 

Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine

Test code: 13086

 

Clinical use

  • Assess misuse of novel/new psychoactive substances (NPS)

Clinical background

NPS, also known as designer or synthetic drugs or “legal highs,” are designed to have similar effects to illicit drugs while circumventing national and international drug scheduling laws.1,2 NPS popularity began to rise in the mid-2000s1 and their use has been reported worldwide.3 Modifications introduced into NPS allow for a large number of diverse chemical structures and make detection using routine drug testing panels challenging.3 NPS can be present in counterfeit drugs; can be more potent than, and/or have potential interactions with, other drugs (prescribed and/or illicit); and have been implicated in overdose and mass poisoning events.1,2 Thus, assessing their presence is important for patient management and public health.

NPS have been defined as natural, synthetic, or semisynthetic substances available in preparations, mixtures, or pure form and fulfilling certain criteria (Table 1).2,4 Signs and symptoms of NPS use can vary based on the type of designer drug (Table 2).1 Perceived legality, affordability, and novelty of NPS can put certain individuals at high risk for NPS misuse and harm (Table 3).1

Table 1. Criteria for Defining NPS

Criteria (must satisfy at least 1) 2

  • Discovered or first synthesized since the mid-2000s and used regardless of degree of psychoactive effect (eg, designer opioid N-pyrrolidino etonitazene and synthetic cannabinoid MDMB-4en-PINACA)
  • Previously discovered, synthesized, or reported but, for the first time in >10 years, observed in the illicit drugs supply or identified in patient specimens (eg, designer opioids 2-methyl AP-237 and isotonitazene)
  • Used in a new or different way from its intended use since the mid-2000s (eg, xylazine "tranq" was approved for veterinary purposes)
  • Previously not well described or studied but now increasingly popular due to an altered toxicological profile (eg, BTMPS in pharmaceutical packaging4)
  • Not controlled by the United Nations drug conventions but with a toxicological profile similar to those listed in the conventions (eg, antipsychotic quetiapine and opioid O-desmethyltramadol)

 

Table 2. NPS Signs and Symptoms

Classes

Examples of signs and symptoms1

Most classes

Anxiety, agitation, delirium, hallucination, hypertension, nausea or vomiting, psychosis, and tachycardia

Designer benzodiazepines and opioids

Aggression, central nervous system depression, confusion, depression, disorientation, paranoia, reduced consciousness, respiratory arrest, respiratory depression, and tachycardia

Synthetic cannabinoids

Acute kidney injury, catatonia, chest pain, confusion, heart palpitations, hyperthermia, liver dysfunction, myocardial infarction, nausea or vomiting, panic attacks, renal dysfunction, respiratory distress, restlessness, rhabdomyolysis, seizure, stroke, and suicidal ideation

 

Table 3. Persons at High Risk for NPS Misuse and Harms

Groups1

  • Persons who use counterfeit prescriptions or inject drugs
  • Persons who are incarcerated or experiencing homelessness or unstable housing
  • School-aged young people
  • Men who have sex with men under influence of drugs (“chemsex”)

 

Definitive testing for characterized NPS is done using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Presumptive testing (eg, immunoassays targeting common, non-NPS, drugs) may detect NPS if there is cross-reactivity; however, confirmatory definitive drug tests will produce negative results. For example, designer benzodiazepines may be detected using benzodiazepine kits but differences in masses between the NPS and the targeted drugs/metabolites will cause presumptive positivity not to be definitively confirmed by LC-MS/MS. To assess whether NPS testing is appropriate when cross-reactivity is suspected, please contact a Quest Diagnostics toxicology specialist as described in the Interpretive Information section below.

Panel testing that simultaneously identifies a broad array of NPS classes using definitive LC-MS/MS-based testing is a means of establishing NPS misuse. Quest offers the Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine Panel (test code 13086), which assesses the presence of different NPS classes (available separately with the test code listed), including

  • Designer benzodiazepines (test code 13793)
  • Designer fentanyl analogs (test code 13794)
  • Designer opioids (test code 13795)
  • Designer stimulants (test code 13796)
  • Other illicit additives (test code 13798)
  • Synthetic cannabinoids (test code 13797)

However, as the list of NPS is rapidly evolving, updates to our tested drug list will be sometimes made based on clinical patient trends, scope recommendations, and trend reports from the Center for Forensic Science Research5 and Quest surveillance data (the NPS-positivity report is downloadable from QuestDiagnostics.com/Healthcare-Professionals/About-our-Tests/Drug-Testing/Novel-Psychoactive-Substances).

Individuals suitable for testing

  • Patients exhibiting signs or symptoms of NPS poisoning (eg, drug-induced psychosis; Table 2), especially those identified as high risk (Table 3)
  • Patients with positive presumptive immunoassay results for known benzodiazepines, opioids, and/or fentanyl but negative confirmatory, definitive LC-MS/MS results
  • Patients being considered for opioid therapy or a change in treatment
  • Patients who need advocacy to verify their abstinence
  • Patients in recovery from substance-use disorder

Method

  • LC-MS/MS
  • Qualitative, class reporting: "positive," "negative," or "interference"
  • Individual analyte cutoffs: 1 to 20 ng/mL
  • No interference from most common illicit and licit drugs of abuse, as well as related compounds; however, structurally similar NPS may preclude detection of ≥1 drugs in the panel

Interpretive information

A “positive” result for a drug class indicates that at least 1 drug or its metabolite has been definitively detected at, or above, the cutoff value for that drug or metabolite. A “negative” result for a drug class indicates that no drugs or metabolites were detected at levels above the cutoff value for those drugs or metabolites.

Cutoffs for individual drugs and their metabolites vary from 1 to 20 ng/mL, but NPS class cutoffs on the report are listed as the highest cutoff within a class (ie, 10 ng/mL with the exception of other illicit additives, which has a highest cutoff of 20 ng/mL for phenibut and BTMPS; Table 4).

An “interference” result for the drug class indicates drug/chemical interference of ≥1 drugs within a drug class, and that results for all other NPS are negative.

These panels are not designed to determine clinical impairment. Assessment of impairment due to NPS misuse should be based on clinical presentation.

For any questions regarding this information or assistance with interpreting these drug test results, please contact a Quest toxicology specialist at 1.877.40.RX TOX (1.877.407.9869). Specialists are available to assist Monday through Friday from 8 AM to 10 PM ET.

References

  1. Peacock A, Bruno R, Gisev N, et al. New psychoactive substances: challenges for drug surveillance, control, and public health responses. Lancet. 2019;394(10209):1668-1684. doi:10.1016/s0140-6736(19)32231-7
  2. Mohr ALA, Logan BK, Fogarty MF, et al. Reports of adverse events associated with use of novel psychoactive substances, 2017–2020: a review. J Anal Toxicol. 2022;46(6):e116-e185. doi:10.1093/jat/bkac023
  3. What are NPS? UNODC Early Warning Advisory on New Psychoactive Substances. Accessed July 25, 2025. https://www.unodc.org/LSS/Page/NPS.
  4. BTMPS. Center for Forensic Science Research & Education. Updated September 3, 2024. Accessed August 5, 2025. https://www.cfsre.org/nps-discovery/monographs/bis2266-tetramethyl-4-piperidyl-sebacate
  5. Trend reports. Center for Forensic Science Research & Education. Updated 2024. Accessed August 20, 2025. https://www.cfsre.org/nps-discovery/trend-reports

Content reviewed 8/2025

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This panel is used to assess misuse of novel/new psychoactive substances (NPS).

Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine

Test Summary

 

Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine

Test code: 13086

 

Clinical use

  • Assess misuse of novel/new psychoactive substances (NPS)

Clinical background

NPS, also known as designer or synthetic drugs or “legal highs,” are designed to have similar effects to illicit drugs while circumventing national and international drug scheduling laws.1,2 NPS popularity began to rise in the mid-2000s1 and their use has been reported worldwide.3 Modifications introduced into NPS allow for a large number of diverse chemical structures and make detection using routine drug testing panels challenging.3 NPS can be present in counterfeit drugs; can be more potent than, and/or have potential interactions with, other drugs (prescribed and/or illicit); and have been implicated in overdose and mass poisoning events.1,2 Thus, assessing their presence is important for patient management and public health.

NPS have been defined as natural, synthetic, or semisynthetic substances available in preparations, mixtures, or pure form and fulfilling certain criteria (Table 1).2,4 Signs and symptoms of NPS use can vary based on the type of designer drug (Table 2).1 Perceived legality, affordability, and novelty of NPS can put certain individuals at high risk for NPS misuse and harm (Table 3).1

Table 1. Criteria for Defining NPS

Criteria (must satisfy at least 1) 2

  • Discovered or first synthesized since the mid-2000s and used regardless of degree of psychoactive effect (eg, designer opioid N-pyrrolidino etonitazene and synthetic cannabinoid MDMB-4en-PINACA)
  • Previously discovered, synthesized, or reported but, for the first time in >10 years, observed in the illicit drugs supply or identified in patient specimens (eg, designer opioids 2-methyl AP-237 and isotonitazene)
  • Used in a new or different way from its intended use since the mid-2000s (eg, xylazine "tranq" was approved for veterinary purposes)
  • Previously not well described or studied but now increasingly popular due to an altered toxicological profile (eg, BTMPS in pharmaceutical packaging4)
  • Not controlled by the United Nations drug conventions but with a toxicological profile similar to those listed in the conventions (eg, antipsychotic quetiapine and opioid O-desmethyltramadol)

 

Table 2. NPS Signs and Symptoms

Classes

Examples of signs and symptoms1

Most classes

Anxiety, agitation, delirium, hallucination, hypertension, nausea or vomiting, psychosis, and tachycardia

Designer benzodiazepines and opioids

Aggression, central nervous system depression, confusion, depression, disorientation, paranoia, reduced consciousness, respiratory arrest, respiratory depression, and tachycardia

Synthetic cannabinoids

Acute kidney injury, catatonia, chest pain, confusion, heart palpitations, hyperthermia, liver dysfunction, myocardial infarction, nausea or vomiting, panic attacks, renal dysfunction, respiratory distress, restlessness, rhabdomyolysis, seizure, stroke, and suicidal ideation

 

Table 3. Persons at High Risk for NPS Misuse and Harms

Groups1

  • Persons who use counterfeit prescriptions or inject drugs
  • Persons who are incarcerated or experiencing homelessness or unstable housing
  • School-aged young people
  • Men who have sex with men under influence of drugs (“chemsex”)

 

Definitive testing for characterized NPS is done using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Presumptive testing (eg, immunoassays targeting common, non-NPS, drugs) may detect NPS if there is cross-reactivity; however, confirmatory definitive drug tests will produce negative results. For example, designer benzodiazepines may be detected using benzodiazepine kits but differences in masses between the NPS and the targeted drugs/metabolites will cause presumptive positivity not to be definitively confirmed by LC-MS/MS. To assess whether NPS testing is appropriate when cross-reactivity is suspected, please contact a Quest Diagnostics toxicology specialist as described in the Interpretive Information section below.

Panel testing that simultaneously identifies a broad array of NPS classes using definitive LC-MS/MS-based testing is a means of establishing NPS misuse. Quest offers the Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine Panel (test code 13086), which assesses the presence of different NPS classes (available separately with the test code listed), including

  • Designer benzodiazepines (test code 13793)
  • Designer fentanyl analogs (test code 13794)
  • Designer opioids (test code 13795)
  • Designer stimulants (test code 13796)
  • Other illicit additives (test code 13798)
  • Synthetic cannabinoids (test code 13797)

However, as the list of NPS is rapidly evolving, updates to our tested drug list will be sometimes made based on clinical patient trends, scope recommendations, and trend reports from the Center for Forensic Science Research5 and Quest surveillance data (the NPS-positivity report is downloadable from QuestDiagnostics.com/Healthcare-Professionals/About-our-Tests/Drug-Testing/Novel-Psychoactive-Substances).

Individuals suitable for testing

  • Patients exhibiting signs or symptoms of NPS poisoning (eg, drug-induced psychosis; Table 2), especially those identified as high risk (Table 3)
  • Patients with positive presumptive immunoassay results for known benzodiazepines, opioids, and/or fentanyl but negative confirmatory, definitive LC-MS/MS results
  • Patients being considered for opioid therapy or a change in treatment
  • Patients who need advocacy to verify their abstinence
  • Patients in recovery from substance-use disorder

Method

  • LC-MS/MS
  • Qualitative, class reporting: "positive," "negative," or "interference"
  • Individual analyte cutoffs: 1 to 20 ng/mL
  • No interference from most common illicit and licit drugs of abuse, as well as related compounds; however, structurally similar NPS may preclude detection of ≥1 drugs in the panel

Interpretive information

A “positive” result for a drug class indicates that at least 1 drug or its metabolite has been definitively detected at, or above, the cutoff value for that drug or metabolite. A “negative” result for a drug class indicates that no drugs or metabolites were detected at levels above the cutoff value for those drugs or metabolites.

Cutoffs for individual drugs and their metabolites vary from 1 to 20 ng/mL, but NPS class cutoffs on the report are listed as the highest cutoff within a class (ie, 10 ng/mL with the exception of other illicit additives, which has a highest cutoff of 20 ng/mL for phenibut and BTMPS; Table 4).

An “interference” result for the drug class indicates drug/chemical interference of ≥1 drugs within a drug class, and that results for all other NPS are negative.

These panels are not designed to determine clinical impairment. Assessment of impairment due to NPS misuse should be based on clinical presentation.

For any questions regarding this information or assistance with interpreting these drug test results, please contact a Quest toxicology specialist at 1.877.40.RX TOX (1.877.407.9869). Specialists are available to assist Monday through Friday from 8 AM to 10 PM ET.

References

  1. Peacock A, Bruno R, Gisev N, et al. New psychoactive substances: challenges for drug surveillance, control, and public health responses. Lancet. 2019;394(10209):1668-1684. doi:10.1016/s0140-6736(19)32231-7
  2. Mohr ALA, Logan BK, Fogarty MF, et al. Reports of adverse events associated with use of novel psychoactive substances, 2017–2020: a review. J Anal Toxicol. 2022;46(6):e116-e185. doi:10.1093/jat/bkac023
  3. What are NPS? UNODC Early Warning Advisory on New Psychoactive Substances. Accessed July 25, 2025. https://www.unodc.org/LSS/Page/NPS.
  4. BTMPS. Center for Forensic Science Research & Education. Updated September 3, 2024. Accessed August 5, 2025. https://www.cfsre.org/nps-discovery/monographs/bis2266-tetramethyl-4-piperidyl-sebacate
  5. Trend reports. Center for Forensic Science Research & Education. Updated 2024. Accessed August 20, 2025. https://www.cfsre.org/nps-discovery/trend-reports

Content reviewed 8/2025

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

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