Human nails have recently become a sample of interest for toxicological purposes. Multiple studies have proven the ability to detect various analytes within the keratin matrix of the nail. The analyte of interest in this study is fentanyl, a highly dangerous and abused drug in recent decades. In this proof-of-concept study, ATR-FTIR was combined with machine learning methods, which are effective in detecting and differentiating fentanyl in samples, to explore whether nail samples are distinguishable from individuals who have used fentanyl and those who have not. PLS-DA and SVM-DA prediction models were created for this study and had an overall accuracy rate of 84.8% and 81.4%, respectively. Notably, when classification was considered at the donor level-i.e., determining whether the donor of the nail sample was using fentanyl-all donors were correctly classified. These results show that ATR-FTIR spectroscopy in combination with machine learning can effectively differentiate donors who have used fentanyl and those who have not and that human nails are a viable sample matrix for toxicology.

Cannabis Facility International Clinical Research Centre St Anne's University Hospital Brno 60200 Brno Czech Republic

Center for Pain Management Department of Anesthesiology and Intensive Care St Anne's University Hospital Brno 60200 Brno Czech Republic

Department of Environmental Toxicology Texas Tech University Lubbock TX 79409 USA

Department of Natural Drugs Faculty of Pharmacy Masaryk University 60200 Brno Czech Republic

See more in PubMed

Busardò F.P., Gottardi M., Pacifici R., Varì M.R., Tini A., Volpe A.R., Giorgetti R., Pichini S. Nails Analysis for Drugs Used in the Context of Chemsex: A Pilot Study. J. Anal. Toxicol. 2020;44:69–74. doi: 10.1093/jat/bkz009. PubMed DOI

Engelhart D.A., Jenkins A.J. Detection of Cocaine Analytes and Opiates in Nails from Postmortem Cases*. J. Anal. Toxicol. 2002;26:489–492. doi: 10.1093/jat/26.7.489. PubMed DOI

Grover C., Bansal S. The nail as an investigative tool in medicine: What a dermatologist ought to know. Indian. J. Dermatol. Venereol. Leprol. 2017;83:635–643. doi: 10.4103/ijdvl.IJDVL_1050_16. PubMed DOI

Sagar G. Nail as Evidence in Forensic Toxicology. Int. Med. Leg. Report. J. 2021;8:99–106.

Shu I., Jones J., Jones M., Lewis D., Negrusz A. Detection of Drugs in Nails: Three Year Experience. J. Anal. Toxicol. 2015;39:624–628. doi: 10.1093/jat/bkv067. PubMed DOI

Toprak S., Kahriman F., Dogan Z., Ersoy G., Can E.Y., Akpolat M., Can M. The potential of Raman and FT-IR spectroscopic methods for the detection of chlorine in human nail samples. Forensic Sci. Med. Pathol. 2020;16:633–640. doi: 10.1007/s12024-020-00313-5. PubMed DOI

Kintz P., Gheddar L., Raul J.S. Testing for anabolic steroids in human nail clippings. J. Forensic Sci. 2021;66:1577–1582. doi: 10.1111/1556-4029.14729. PubMed DOI

Daniel C.R., 3rd, Piraccini B.M., Tosti A. The nail and hair in forensic science. J. Am. Acad. Dermatol. 2004;50:258–261. doi: 10.1016/j.jaad.2003.06.008. PubMed DOI

Sharma A., Verma R., Kumar R., Chauhan R., Sharma V. Chemometric analysis of ATR-FTIR spectra of fingernail clippings for classification and prediction of sex in forensic context. Microchem. J. 2020;159:105504. doi: 10.1016/j.microc.2020.105504. DOI

Go M.D., Al-Delaimy W.K., Schilling D., Vuylsteke B., Mehess S., Spindel E.R., McEvoy C.T. Hair and nail nicotine levels of mothers and their infants as valid biomarkers of exposure to intrauterine tobacco smoke. Tob. Induc. Dis. 2021;19:100. doi: 10.18332/tid/143209. PubMed DOI PMC

Mari F., Politi L., Bertol E. Nails of newborns in monitoring drug exposure during pregnancy. Forensic Sci. Int. 2008;179:176–180. doi: 10.1016/j.forsciint.2008.06.001. PubMed DOI

Paul R., Tsanaclis L., Murray C., Boroujerdi R., Facer L., Corbin A. Ethyl Glucuronide as a Long-term Alcohol Biomarker in Fingernail and Hair. Matrix Comparison and Evaluation of Gender Bias. Alcohol Alcohol. 2019;54:402–407. doi: 10.1093/alcalc/agz015. PubMed DOI

Irving R.D., Dickson S. The detection of sedatives in hair and nail samples using tandem LC-MS-MS. Forensic Sci. Int. 2007;166:58–67. doi: 10.1016/j.forsciint.2006.03.027. PubMed DOI

Mitu B., Cerda M., Hrib R., Trojan V., Halámková L. Attenuated Total Reflection Fourier Transform Infrared Spectroscopy for Forensic Screening of Long-Term Alcohol Consumption from Human Nails. ACS Omega. 2023;8:22203–22210. doi: 10.1021/acsomega.3c02579. PubMed DOI PMC

Rab E., Flanagan R.J., Hudson S. Detection of fentanyl and fentanyl analogues in biological samples using liquid chromatography–high resolution mass spectrometry. Forensic Sci. Int. 2019;300:13–18. doi: 10.1016/j.forsciint.2019.04.008. PubMed DOI

Suzuki J., El-Haddad S. A review: Fentanyl and non-pharmaceutical fentanyls. Drug Alcohol Depend. 2017;171:107–116. doi: 10.1016/j.drugalcdep.2016.11.033. PubMed DOI

National Institute on Drug Abuse Drug Overdose Death Rates [Internet] [(accessed on 14 December 2024)]; National Institute on Drug Abuse. National Institutes of Health; 2024. Available online: https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates.

Razlansari M., Ulucan-Karnak F., Kahrizi M., Mirinejad S., Sargazi S., Mishra S., Rahdar A., Díez-Pascual A.M. Nanobiosensors for detection of opioids: A review of latest advancements. Eur. J. Pharm. Biopharm. 2022;179:79–94. doi: 10.1016/j.ejpb.2022.08.017. PubMed DOI

Crocombe R.A., Giuntini G., Schiering D.W., Profeta L.T.M., Hargreaves M.D., Leary P.E., Brown C.D., Chmura J.W. Field-portable detection of fentanyl and its analogs: A review. J. Forensic Sci. 2023;68:1570–1600. doi: 10.1111/1556-4029.15355. PubMed DOI

Mitu B., Trojan V., Hrib R., Halámková L. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) analysis of human nails: Implications for age determination in forensics. J. Forensic Sci. 2024;70:150–160. doi: 10.1111/1556-4029.15641. PubMed DOI

Mitu B., Trojan V., Halámková L. Sex Determination of Human Nails Based on Attenuated Total Reflection Fourier Transform Infrared Spectroscopy in Forensic Context. Sensors. 2023;23:9412. doi: 10.3390/s23239412. PubMed DOI PMC

Takamura A., Halamkova L., Ozawa T., Lednev I.K. Phenotype Profiling for Forensic Purposes: Determining Donor Sex Based on Fourier Transform Infrared Spectroscopy of Urine Traces. Anal. Chem. 2019;91:6288–6295. doi: 10.1021/acs.analchem.9b01058. PubMed DOI

Green T.C., Park J., Gilbert M., McKenzie M., Struth E., Lucas R., Clarke W., Sherman S.G. An assessment of the limits of detection, sensitivity and specificity of three devices for public health-based drug checking of fentanyl in street-acquired samples. Int. J. Drug Policy. 2020;77:102661. doi: 10.1016/j.drugpo.2020.102661. PubMed DOI

McCrae K., Tobias S., Tupper K., Arredondo J., Henry B., Mema S., Wood E., Ti L. Drug checking services at music festivals and events in a Canadian setting. Drug Alcohol. Depend. 2019;205:107589. doi: 10.1016/j.drugalcdep.2019.107589. PubMed DOI

Ramsay M., Gozdzialski L., Larnder A., Wallace B., Hore D. Fentanyl quantification using portable infrared absorption spectroscopy. A framework for community drug checking. Vib. Spectrosc. 2021:114. doi: 10.1016/j.vibspec.2021.103243. DOI

Ti L., Tobias S., Lysyshyn M., Laing R., Nosova E., Choi J., Arredondo J., McCrae K., Tupper K., Wood E. Detecting fentanyl using point-of-care drug checking technologies: A validation study. Drug Alcohol Depend. 2020;212:108006. doi: 10.1016/j.drugalcdep.2020.108006. PubMed DOI

Liu P., Liu W., Qiao H., Jiang S., Wang Y., Chen J., Su M., Di B. Simultaneous quantification of 106 drugs or their metabolites in nail samples by UPLC-MS/MS with high-throughput sample preparation: Application to 294 real cases. Anal. Chim. Acta. 2022;1226:340170. doi: 10.1016/j.aca.2022.340170. PubMed DOI

Biancolillo A., Marini F., Ruckebusch C., Vitale R. Chemometric Strategies for Spectroscopy-Based Food Authentication. Appl. Sci. 2020;10:6544. doi: 10.3390/app10186544. DOI

Rutledge D.N., Roger J.-M., Lesnoff M. Different Methods for Determining the Dimensionality of Multivariate Models. Front. Anal. Sci. 2021;1:754447. doi: 10.3389/frans.2021.754447. DOI

Yan B., Li Y., Yang G., Wen Z.N., Li M.L., Li L.J. Discrimination of parotid neoplasms from the normal parotid gland by use of Raman spectroscopy and support vector machine. Oral Oncol. 2011;47:430–435. doi: 10.1016/j.oraloncology.2011.02.021. PubMed DOI

Hands J.R., Abel P., Ashton K., Dawson T., Davis C., Lea R.W., McIntosh A.J.S., Baker M.J. Investigating the rapid diagnosis of gliomas from serum samples using infrared spectroscopy and cytokine and angiogenesis factors. Anal. Bioanal. Chem. 2013;405:7347–7355. doi: 10.1007/s00216-013-7163-z. PubMed DOI

Cortes C., Vapnik V. Support-Vector Networks. Mach. Learn. 1995;20:273–297. doi: 10.1007/BF00994018. DOI

Huang C.-L., Wang C.-J. A GA-based feature selection and parameters optimizationfor support vector machines. Expert Syst. Appl. 2006;31:231–240. doi: 10.1016/j.eswa.2005.09.024. DOI

Azies H.A., Trishnanti D., Mustikawati P.H.E. Comparison of Kernel Support Vector Machine (SVM) in Classification of Human Development Index (HDI); Proceedings of the 1st International Conference on Global Development—ICODEV; Surabaya, Indonesia. 19 November 2019; p. 53.

Barton P.M. A Forensic Investigation of Single Human Hair Fibres Using FTIR-ATR Spectroscopy and Chemometrics. Queensland University of Technology; Brisbane City, QLD, Australia: 2011.

Coroaba A., Pinteala T., Chiriac A., Chiriac A.E., Simionescu B.C., Pinteala M. Degradation Mechanism Induced by Psoriasis in Human Fingernails: A Different Approach. J. Investig. Dermatol. 2016;136:311–313. doi: 10.1038/JID.2015.387. PubMed DOI

Ogawa N., Higashi K., Nagase H., Endo T., Moribe K., Loftsson T., Yamamoto K., Ueda H. Effects of cogrinding with β-cyclodextrin on the solid state fentanyl. J. Pharm. Sci. 2010;99:5019–5029. doi: 10.1002/jps.22193. PubMed DOI

Mendez K.M., Reinke S.N., Broadhurst D.I. A comparative evaluation of the generalised predictive ability of eight machine learning algorithms across ten clinical metabolomics data sets for binary classification. Metabolomics. 2019;15:150. doi: 10.1007/s11306-019-1612-4. PubMed DOI PMC

DeLong E.R., DeLong D.M., Clarke-Pearson D.L. Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach. Biometrics. 1988;44:837–845. doi: 10.2307/2531595. PubMed DOI

Crepeault H., Socias M.E., Tobias S., Lysyshyn M., Custance A., Shapiro A., Ti L. Examining fentanyl and its analogues in the unregulated drug supply of British Columbia, Canada using drug checking technologies. Drug Alcohol Rev. 2023;42:538–543. doi: 10.1111/dar.13580. PubMed DOI PMC