Forensic Sciences Research, Volume. 9, Issue 1, owae001(2024)

How new nanotechnologies are changing the opioid analysis scenery? A comparison with classical analytical methods

Muhammad Usman1,2, Yawar Baig1, Donatella Nardiello2, and Maurizio Quinto2、*
Author Affiliations
  • 1Narcotic Unit, Punjab Forensic Science Agency, Home Department, Government of The Punjab, Lahore-54000, Pakistan
  • 2Department of Sciences of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, I-71122 Foggia, Italy
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    Figures & Tables(6)
    (A) Poppy plant material and (B) raw opium.
    Chemical structures of supramolecular sensors (S1– S3) used for the analysis of opioids and their metabolites.
    • Table 0. List of the most common opioids and their use.

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      Table 0. List of the most common opioids and their use.

      OpioidsDescriptionPharmaceutical useLegal status [49]
      3-MonoacetylmorphineSemisynthetic, inactive metabolite of heroin with weak affinity for μ-receptorsProhibited, schedule I
      6-MonoacetylmorphineSemisynthetic, metabolite of heroin produced by acetylation of morphineProhibited
      AcetylcodeineSemisynthetic, by-product of acetylation of codeine in poppy resin
      AcetylfentanylSynthetic, analogue of fentanyl and fifteen times more potent than morphineNever been licenced for medical useIllegal, not prescriptible, schedule I
      AcrylfentanylSynthetic, analogue of fentanyl, and designer drugAnalgesicControlled, not prescriptible, schedule I
      AlfentanilSynthetic, analogue of fentanylAnalgesic, used as anaesthesiaControlled, schedule II
      BuprenorphineSynthetic and used to treat opioid addictionUsed to treat chronic painPrescription drug, schedule III
      CarfentanilSynthetic, analogue of fentanyl, 1 000 times more potent than heroinUsed in veterinary medicineControlled, schedule II
      CodeineNatural, constituent of poppy resin, less potent than morphineAnalgesic and antitussiveControlled, schedule II
      DextromethorphanSynthetic, approved for medical use in 1953Cough suppressantPharmacy medicine
      DextrorphanSyntheticAntitussiveUnscheduled
      DihydrocodeineSemisynthetic, derived from codeine, twice as strong as codeineAnalgesic and antitussivePrescription drug, schedule II
      HeroinSemisynthetic, first derived from morphine in 1874AnalgesicProhibited, schedule I
      HydrocodoneSemisynthetic, derived from codeineAnalgesic, antitussiveControlled, schedule I
      HydromorphoneSemisynthetic, derived from morphineUsed to treat severe painControlled, schedule II
      MethadoneSynthetic opioidUsed to treat chronic painControlled, schedule II
      MetoponMethylated derivative of hydromorphoneUsed to treat chronic painControlled, schedule II
      MorphineNatural, constituent of poppy resinAnalgesicControlled, schedule II
      Morphine-3-glucuronideMetabolite of morphine
      Morphine-6-glucuronideMetabolite of morphine, stronger μ-receptors affinity than morphine
      NicocodeineSemisyntheticAnalgesic and cough suppressantProhibited, not prescriptible, schedule I
      NormorphineSemisynthetic, derived from morphine; one-fourth as active as morphineAnalgesicProhibited, schedule I
      NorpethidineSynthetic, precursor in the synthesis of other drugsAnalgesicControlled, schedule II
      NoscapineNatural, constituent of poppy resinAntitussiveUncontrolled
      OxycodoneSemisynthetic, first derived from thebaine in 1916AnalgesicControlled, schedule II
      OxymorpholMetabolite of oxymorphone; can be manufacturedAnalgesic and cough suppressant
      OxymorphoneSemisyntheticAnalgesic, used to treat severe painControlled, not prescriptible, schedule I
      PapaverineNatural, constituent of poppy resinAntispasmodicPrescription-only
      PentazocineSynthetic, approved for medical use in 1964Pain killerControlled, schedule IV
      PethidineSynthetic opioidPain relievesControlled, schedule II
      PholcodineSemisynthetic alkaloidOpioid cough suppressantPrescription drug in dose, schedule I
      RemifentanilSynthetic, analogue of fentanyl, used for general anaesthesiaPain relievers and anaestheticControlled, schedule II
      SufentanilSynthetic, analogue of fentanyl, 500 times more potent than morphineAnalgesic, used as anaesthesiaControlled, schedule II
      ThebaineNatural, constituent of poppy resinControlled, schedule II
      TilidineSynthetic opioidPain killerHigh-dose prescription drug, schedule I
      TramadolSynthetic opioidPain relievesPrescription drug, schedule IV
    • Table 0. List of drug abuse analyses carried out by classical techniques, with the indication of analyzed opioids/opioids, matrices, limit of detections (LODs), and limit of quantitations (LOQs).

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      Table 0. List of drug abuse analyses carried out by classical techniques, with the indication of analyzed opioids/opioids, matrices, limit of detections (LODs), and limit of quantitations (LOQs).

      ReferencesDrug abuse analyzedTechniqueSampleLODLOQ
      [20]MorphineGC–MSLiver, kidney, hair, and teeth
       6-MAM 
       Codeine    
      [70]6-MAMGC–MSBone0.1 ng/mg0.3 ng/mg
       Morphine  0.3 ng/mg1 ng/mg
       Tramadol  0.2 ng/mg0.5 ng/mg
       Methadone  0.3 ng/mg0.8 ng/mg
      [82]MethadoneGC–MSHair0.05 ng/mg0.16 ng/mg
      [83]MethadoneGC–MSHair0.15 ng/mg0.36 ng/mg
      [12]HeroinGC–MSStreet sample
      [84]MorphineGC–MSHair0.016 ng/mg0.046 ng/mg
       Codeine  0.016 ng/mg0.045 ng/mg
       6-MAM  0.015 ng/mg0.043 ng/mg
       Methadone  0.016 ng/mg0.042 ng/mg
      [85]FentanylGC–MSPlasma0.03 ng/mg0.1 ng/mg
      [86]MorphineGC–MSBlood2 ng/mg10 ng/mg
       Codeine    
       6-MAM    
       Hydrocodone    
       Hydromorphone    
       Oxycodone    
       Oxymorphone    
      [87]MorphineGC–MSUrine10 ng/mg25 ng/mg
       Codeine    
       6-MAM    
       Hydrocodone    
       Hydromorphone    
       Oxycodone    
       Oxymorphone    
      [18]CodeineGC–MS/MSBlood1 ng/mg for all 2.5 ng/mg for hydrocodone2.5 ng/mg for all 5 ng/mg for hydrocodone
       Morphine  
       6-MAM  
       Hydrocodone    
       Hydromorphone    
      [79]Morphine,GC-VUVStreet drug samples
       3-MAMVacuum ultraviolet   
       6-MAMspectrophotometry   
       Heroin    
       Codeine    
      [88]HeroinGC-FIDStreet drug samples0.02 mg/mL0.05 mg/mL
      [89]MorphineLC–MS/MSBlood16 ng/mg 
      [90]MorphineLC–MS/MSSerum, urine and0.01–1.7 ng/mg0.04–4.2 ng/mg
       Codeine post-mortem blood  
       Methadone    
      [91]Fentanyl derivatives and metabolitesLC–MS/MSOral fluid0.05–0.50 ng/mg0.1–1.0 ng/mg
      [92]MorphineLC–MS/MSHair2.0 pg/mg5.0 pg/mg
       Codeine    
       6-MAM    
      [93]MorphineLC–MS/MSOral fluid0.8–2 ng/mg2–5 ng/mg
       Codeine    
       6-MAM    
      [94]MorphineLC–MS/MSHair3.8 pg/mg12 pg/mg
       Codeine  4.7 pg/mg16 pg/mg
       6-MAM  4.2 pg/mg14 pg/mg
      [23]6-MAMLC–MS/MSHair25 pg/mg100 pg/mg
       Morphine  5.0 pg/mg10 pg/mg
       Codeine  2.0 pg/mg10 pg/mg
       Hydromorphone  1.0 pg/mg5 pg/mg
       Hydrocodone  4.0 pg/mg10 pg/mg
      [95]BuprenorphineLC-DEDPlasma0.08 ng/mg 
       Norbuprenorphine  0.08 ng/mg 
       Naloxone  0.04 ng/mg 
       Methadone  0.9 ng/mg 
      [58]MethadoneHPLC-MS/MSPostmortem samples2.5 ng/mg5 ng/mg
      [26]MorphineHPLCStreet samples1 ng/mg5 ng/mg
      [96]MorphineHPLC-PDAPostmortem urine10–25 μg/L-
       Codeine    
       Methadone    
      [75]FentanylUHPLC–MS/MSHair0.1–0.3 pg/mg for all 1.5 pg/mg for oxycodone0.3–0.9 pg/mg for all, 1.5 pg/mg for noroxycodone
       Furanylfentanyl  
       Oxycodone  
       Hydrocodone    
       Tramadol    
       Morphine    
       6-MAM    
       Codeine    
      [97]MorphineHPLC-DADHair0.2 ng/mg
       Codeine    
       6-MAM    
      [98]OcfentanilUHPLC–MS/MSPostmortem body samples0.03 ng/mg0.10 ng/mg
      [99]HeroinICP-MSStreet drug
      [100]HeroinICP-MSStreet drug0.001–100 ng/g0.1–500 ng/g
      [101]HeroinATR-FTIRStreet drug
      [67]HeroinDR-NIRStreet drug
      [102]Heroin (characterization)1H NMRStreet drug
      [14]CodeineCapillaryPharmaceutical15 μmol/L
       TramadolElectrophoresispreparations0.62 μmol/L 
    • Table 0. Colour tests used for preliminary opioid screenings.

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      Table 0. Colour tests used for preliminary opioid screenings.

      Test nameAnalyteColour expressionReference
      MarquisCodeine, morphine, heroinViolet, reddish-purple[53]
      FroehdeCodeine, morphine, heroinPurple, green[54]
      Meck's testCodeine, morphine, heroinBlue, green[55]
      Nitric acidHeroinRed-orange, green[56]
      OliverHeroinPink, red[57]
      MandelinCodeine, heroin, morphineBlue-green, blue-grey, light grey[53]
      LiebermanCodeine, morphineBlack[53]
      AuNPsCodeineGreen[51]
    • Table 0. List of drug abuse analyses carried out by electrochemical techniques, with the indication of nanomaterials/nanobiosensors, matrices, and limit of detections (LODs).

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      Table 0. List of drug abuse analyses carried out by electrochemical techniques, with the indication of nanomaterials/nanobiosensors, matrices, and limit of detections (LODs).

      ReferenceDrug abuse analyzedTechnique usedNanomaterial/nanobiosensorSampleLOD (nmol/L)
      [135]Heroin, morphine, and noscapineDifferential pulse voltammetryGNSsDrug sample400, 500, and 200
      [35]CodeineSquare wave voltammetryGNSs/NafionUrine and cough syrup15
      [136]CodeineSquare wave voltammetryGNSs—CoFe2O4 nanoparticlesBlood, urine, and pharmaceutical tablets11
      [105]MorphineLinear sweep voltammetryAuNPsUrine and pharmaceutical tablets0.43
      [137]HeroinCapillary electrophoresis mass spectrometryAuNPsDrug sample 
      [103]MorphineDifferential pulse voltammetryAuNPsUrine1.33
      [138]MorphineCyclic voltammetryAuNPsUrine210
      [139]MorphineCyclic voltammetry and differential pulse voltammetryAuNPsUrine4.21
      [140]MorphineCyclic voltammetry and differential pulse voltammetryAuNPs/ferroceneUrine3.51
      [141]CodeineDifferential pulse voltammetry, cyclic voltammetry, and chronoamperometryMWCNTsSerum, urine, and pharmaceutical preparations200
      [142]MorphineCyclic voltammetryMWCNTs/NafionSerum32
      [143]MorphineCyclic voltammetry and chronoamperometryN-hexyl-3-methylimidazolium hexafluoro phosphate/MWCNTsUrine and pharmaceutical injection20
      [144]Codeine and morphineDifferential pulse voltammetry, cyclic voltammetry, and chronoamperometryMWCNTs/SnO2-Zn2SnO4 NanoparticlesUrine9 for both
      [34]CodeineDifferential pulse voltammetrySWCNTsUrine, pharmaceutical tablets110
      [145]Codeine and morphineDifferential pulse voltammetryZn2SO4 nanoparticles/graphene nanocompositeUrine and pharmaceutical syrup9 and 11
      [146]MorphineCyclic voltammetryZnO/CNTsUrine60
      [46]MorphineCyclic voltammetry and square wave voltammetryNickel oxide/carbon nanotubes (NiO/CNTs)Urine and pharmaceutical sample10
      [36]CodeineDifferential pulse voltammetryWO3-CNTsUrine20
      [37]CodeineDifferential pulse voltammetryPorous silicon/palladium nanoparticlesSerum, urine, and pharmaceutical preparations300
      [51]MorphineCyclic voltammetry, linear sweep voltammetry, and square wave voltammetryPt nanoparticlesPharmaceutical tablets50
      [38]Morphine and codeineAdsorptive stripping voltammetryPt nanoparticle/porous siliconBlood and urine30 and 20
      [147]FentanylCyclic voltammetryRu(bpy)3Cl2Drug sample8.5
      [106]MorphineCyclic voltammetry and linear sweep voltammetryER-MWCNTs-doped-GOBlood and urine200
      [43]MorphineDifferential pulse voltammetry, cyclic voltammetry, and chronoamperometryMWCNTs/chitosanBlood and urine240
      [103]MorphineCyclic voltammetry and chronoamperometryVinylferrocene/MWCNTsUrine and pharmaceutical sample90
      [51]CodeineColourimetryCitrate stabilized AuNPsPostmortem blood900
      [104]MorphineDifferential pulse voltammetryAuNPsUrine1.33
      [145]MorphineDifferential pulse voltammetryZn2SnO4-GO/CPEPlasma11
      [148]Codeine, morphine, thebaine, oxycodone, noroxycodone, tramadol, and methadoneColourimetryAuNPsDrugs in aqueous media and urine
      [79]MorphineVoltammetryBaFe12O19 NPs20
      [149]MorphineDifferential pulse voltammetryLa3+-CuO/MWCNTs/CPE 8.0
      [150]MethadoneDifferential pulse voltammetry(PDDA)/MWCNT/CQDsUrine and plasma30
      [151]MorphineDifferential pulse voltammetryRGO-PdUrine13
      [152]MorphineCyclic voltammetryOMC/GCEUrine10
      [153]MorphineCyclic voltammetryAuNPs/GCESerum41
      [154]CodeineDifferential pulse voltammetryMWCNTs/ZnCrFeO4/CPETablets, cough syrup, urine, and serum9
      [155]MethadoneCyclic voltammetryYb2O3NP-Ru(bpy)3+2-CPEUrine0.2
      [156]Morphine and buprenorphineDifferential pulse voltammetryRh NPs-MC/GCEPharmaceutical tablets40
      [157]MethadoneDifferential pulse voltammetry(Gr/AgNPs)2/GCEBlood120
      [158]MorphineSquare wave voltammetryFeWO4/CPEUrine580
      [127]Morphine and CodeineDifferential pulse voltammetrydsDNA/MWCNTs– PDDA/PGEBlood, serum, urine, and pharmaceutical formulations600
      [143]MorphineCyclic voltammetry, ChronoamperometryN-hexyl-3-methylimidazolium hexafluorophosphate/MWCNTs/PEUrine and pharmaceutical injections20
      [125]MorphineOptical dipstick kitAuNP-labelled morphine scFv-immunoprobeBlood, urine, and saliva20
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    Muhammad Usman, Yawar Baig, Donatella Nardiello, Maurizio Quinto. How new nanotechnologies are changing the opioid analysis scenery? A comparison with classical analytical methods[J]. Forensic Sciences Research, 2024, 9(1): owae001

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    Paper Information

    Category: Research Articles

    Received: Jun. 22, 2023

    Accepted: Jan. 2, 2024

    Published Online: Sep. 22, 2025

    The Author Email: Maurizio Quinto (maurizio.quinto@unifg.it)

    DOI:10.1093/fsr/owae001

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