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Nail analysis for the detection of drugs of abuse and pharmaceuticals: a review

Abstract

Nails can stably accumulate substances for long periods of time, thus providing retrospective information regarding drugs of abuse and pharmaceutical use. Nails have several advantages over the conventional matrices, such as blood and urine, including a longer detection window (months to years), non-invasive sample collection, and easy storage and transport. These aspects make nails a very interesting matrix for forensic and clinical toxicology. Because of the low concentrations of drugs of abuse and pharmaceuticals present in nails and the complexity of the keratinized matrix, analytical methods need to be more sensitive, and sample preparation is crucial. This review summarizes the literature regarding the detection and quantification of drugs of abuse and pharmaceuticals in nails, as well as the employed pre-analytical and analytical techniques. Additionally, the applications of nail analysis are reviewed. Finally, an overview of the challenges of nail analysis is provided, and guidelines for future research are proposed.

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References

  1. Palmeri A, Pichini S, Pacifici R, Zuccaro P, Lopez A (2000) Drugs in nails: physiology, pharmacokinetics and forensic toxicology. Clin Pharmacokinet 38:95–110

    CAS  PubMed  Article  Google Scholar 

  2. Daniel CR, Piraccini BM, Tosti A (2004) The nail and hair in forensic science. J Am Acad Dermatol 50:258–261

    PubMed  Article  Google Scholar 

  3. Lander H, Hodge PR, Crisp CS (1965) Arsenic in the hair and nails: its significance in acute arsenical poisoning. J Forensic Med 12:52–67

    CAS  PubMed  Google Scholar 

  4. Pounds CA, Pearson EF, Turner TD (1979) Arsenic in fingernails. J Forensic Sci Soc 19:165–173

    CAS  PubMed  Article  Google Scholar 

  5. Alexiou D, Koutselinis A, Manolidis C, Boukis D, Papadatos J, Papadatos C (1980) The content of trace elements (Cu, Zn, Fe, Mg) in fingernails of children. Dermatologica 160:380–382

    CAS  PubMed  Article  Google Scholar 

  6. Wilhelm M, Hafner D, Lombeck I, Ohnesorge FK (1991) Monitoring of cadmium, copper, lead and zinc status in young children using toenails: comparison with scalp hair. Sci Total Environ 103:199–207

    CAS  PubMed  Article  Google Scholar 

  7. Gerhardsson L, Englyst V, Lundstrom NG, Nordberg G, Sandberg S, Steinvall F (1995) Lead in tissues of deceased lead smelter workers. J Trace Elem Med Biol 9:136–143

    CAS  PubMed  Article  Google Scholar 

  8. Suzuki O, Hattori H, Asano M (1984) Nails as useful materials for detection of methamphetamine or amphetamine abuse. Forensic Sci Int 24:9–16

    CAS  PubMed  Article  Google Scholar 

  9. Gupchup GV, Zatz JI (1999) Structural characteristics and permeability properties of the human nail: a review. J Cosmet Sci 50:363–385

    CAS  Google Scholar 

  10. Ropero-Miller JD, Goldberger BA, Cone EJ, Joseph RE Jr (2000) The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration. J Anal Toxicol 24:496–508

    CAS  PubMed  Article  Google Scholar 

  11. Hang C, Ping X, Min S (2013) Long-term follow-up analysis of zolpidem in fingernails after a single oral dose. Anal Bioanal Chem 405:7281–7289

    CAS  PubMed  Article  Google Scholar 

  12. Madry MM, Steuer AE, Binz TM, Baumgartner MR, Kraemer T (2014) Systematic investigation of the incorporation mechanisms of zolpidem in fingernails. Drug Testing and Anal 6:533–541

    CAS  Article  Google Scholar 

  13. Engelhart DA, Jenkins AJ (2002) Detection of cocaine analytes and opiates in nails from postmortem cases. J Anal Toxicol 26:489–492

    CAS  PubMed  Article  Google Scholar 

  14. Marieb EN (2012) Essentials of human anatomy and physiology, 10th edn. Pearson, New Jersey

    Google Scholar 

  15. Fleckman P (1985) Anatomy and physiology of the nail. Dermatol Clin 3:373–381

    CAS  PubMed  Google Scholar 

  16. Lin D-L, Yin R-M, Liu H-C, Wang C-Y, Liu RH (2004) Deposition characteristics of methamphetamine and amphetamine in fingernail clippings and hair sections. J Anal Toxicol 28:411–417

    CAS  PubMed  Article  Google Scholar 

  17. de la Torre R, Farre M, Navarro M, Pacifici R, Zuccaro P, Pichini S (2004) Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices. Clin Pharmacokinet 43:157–185

    PubMed  Article  Google Scholar 

  18. Pragst F, Balikova MA (2006) State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chim Acta 370:17–49

    CAS  PubMed  Article  Google Scholar 

  19. Kronstrand R, Förstberg-Peterson S, KÅgedal B, Ahlner J, Larson G (1999) Codeine concentration in hair after oral administration is dependent on melanin content. Clin Chem 45:1485–1494

    CAS  PubMed  Google Scholar 

  20. Testorf MF, Kronstrand R, Svensson SPS, Lundström I, Ahlner J (2001) Characterization of [3H]flunitrazepam binding to melanin. Anal Biochem 298:259–264

    CAS  PubMed  Article  Google Scholar 

  21. Suzuki S, Inoue T, Hori H, Inayama S (1989) Analysis of methamphetamine in hair, nail, sweat, and saliva by mass fragmentography. J Anal Toxicol 13:176–178

    CAS  PubMed  Article  Google Scholar 

  22. Cirimele V, Kintz P, Mangin P (1995) Detection of amphetamines in fingernails: an alternative to hair analysis. Arch Toxicol 70:68–69

    CAS  PubMed  Article  Google Scholar 

  23. Kim JY, Cheong JC, Kim MK, Lee JI, In MK (2008) Simultaneous determination of amphetamine-type stimulants and cannabinoids in fingernails by gas chromatography-mass spectrometry. Arch Pharm Res 31:805–813

    CAS  PubMed  Article  Google Scholar 

  24. Kim JY, Shin SH, In MK (2010) Determination of amphetamine-type stimulants, ketamine and metabolites in fingernails by gas chromatography-mass spectrometry. Forensic Sci Int 194:108–114

    CAS  PubMed  Article  Google Scholar 

  25. Kim JY, Cheong JC, Lee JI, Son JH, In MK (2012) Rapid and simple GC-MS method for determination of psychotropic phenylalkylamine derivatives in nails using micro-pulverized extraction. J Forensic Sci 57:228–233

    CAS  PubMed  Article  Google Scholar 

  26. Cingolani M, Scavella S, Mencarelli R, Mirtella D, Froldi R, Rodriguez D (2004) Simultaneous detection and quantitation of morphine, 6-acetylmorphine, and cocaine in toenails: comparison with hair analysis. J Anal Toxicol 28:128–131

    CAS  PubMed  Article  Google Scholar 

  27. Skopp G, Potsch L (1997) A case report on drug screening of nail clippings to detect prenatal drug exposure. Ther Drug Monit 19:386–389

    CAS  PubMed  Article  Google Scholar 

  28. Engelhart DA, Lavins ES, Sutheimer CA (1998) Detection of drugs of abuse in nails. J Anal Toxicol 22:314–318

    CAS  PubMed  Article  Google Scholar 

  29. Garside D, Ropero-Miller JD, Goldberger BA, Hamilton WF, Maples WR (1998) Identification of cocaine analytes in fingernail and toenail specimens. J Forensic Sci 43:974–979

    CAS  PubMed  Google Scholar 

  30. Ragoucy-Sengler C, Kintz P (2005) Detection of smoked cocaine marker (anhydroecgonine methylester) in nails. J Anal Toxicol 29:765–768

    CAS  PubMed  Article  Google Scholar 

  31. Valente-Campos S, Yonamine M, de Moraes Moreau RL, Silva OA (2006) Validation of a method to detect cocaine and its metabolites in nails by gas chromatography-mass spectrometry. Forensic Sci Int 159:218–222

    CAS  PubMed  Article  Google Scholar 

  32. Mari F, Politi L, Bertol E (2008) Nails of newborns in monitoring drug exposure during pregnancy. Forensic Sci Int 179:176–180

    CAS  PubMed  Article  Google Scholar 

  33. Garside D (2008) Drugs-of-abuse in nails. In: Jenkins A, Caplan Y (eds) Drug testing in alternate biological specimens. Forensic science and medicine. Humana Press, New York, pp 43–65

    Chapter  Google Scholar 

  34. Jenkins AJ, Goldberger BA (1997) Identification of unique cocaine metabolites and smoking by-products in postmortem blood and urine specimens. J Forensic Sci 42:824–827

    CAS  PubMed  Google Scholar 

  35. Ali EA, Edwards HM, Hargreaves M, Scowen I (2008) Raman spectroscopic investigation of cocaine hydrochloride on human nail in a forensic context. Anal Bioanal Chem 390:1159–1166

    CAS  PubMed  Article  Google Scholar 

  36. Lemos NP, Anderson RA, Valentini R, Tagliaro F, Scott RT (2000) Analysis of morphine by RIA and HPLC in fingernail clippings obtained from heroin users. J Forensic Sci 45:407–412

    CAS  PubMed  Google Scholar 

  37. Lemos NP, Anderson RA, Robertson JR (2000) The analysis of methadone in nail clippings from patients in a methadone-maintenance program. J Anal Toxicol 24:656–660

    CAS  PubMed  Article  Google Scholar 

  38. Shen M, Chen H, Xiang P (2014) Determination of opiates in human fingernail—Comparison to hair. J Chromatogr B 967:84–89

    CAS  Article  Google Scholar 

  39. Jones J, Jones M, Plate C, Lewis D (2013) The detection of THCA using 2-dimensional gas chromatography-tandem mass spectrometry in human fingernail clippings: method validation and comparison with head hair. Am J Anal Chem 4:1–8

    Article  Google Scholar 

  40. Lemos NP, Anderson RA, Robertson JR (1999) Nail analysis for drugs of abuse: extraction and determination of cannabis in fingernails by RIA and GC-MS. J Anal Toxicol 23:147–152

    CAS  PubMed  Article  Google Scholar 

  41. Jones J (2012) Liquid chromatography-tandem mass spectrometry assay to detect ethyl glucuronide in human fingernail: comparison to hair and gender differences. Am J Anal Chem 3:83–91

    CAS  Article  Google Scholar 

  42. Morini L, Colucci M, Ruberto MG, Groppi A (2012) Determination of ethyl glucuronide in nails by liquid chromatography tandem mass spectrometry as a potential new biomarker for chronic alcohol abuse and binge drinking behavior. Anal Bioanal Chem 402:1865–1870

    CAS  PubMed  Article  Google Scholar 

  43. Morini L, Marchei E, Tarani L, Trivelli M, Rapisardi G, Elicio MR, Ramis J, Garcia-Algar O, Memo L, Pacifici R, Groppi A, Danesino P, Pichini S (2013) Testing ethylglucuronide in maternal hair and nails for the assessment of fetal exposure to alcohol: comparison with meconium testing. Ther Drug Monit 35:402–407

    CAS  PubMed  Article  Google Scholar 

  44. Keten A, Zeren C, Arslan MM, Daglioglu N, Karanfil R, Sen BB (2013) Determination of ethyl glucuronide in fingernails by LC/MS-MS. Rom J Leg Med 21:67–72

    Article  Google Scholar 

  45. Berger L, Fendrich M, Jones J, Fuhrmann D, Plate C, Lewis D (2014) Ethyl glucuronide in hair and fingernails as a long-term alcohol biomarker. Addiction 109:425–431

    PubMed Central  PubMed  Article  Google Scholar 

  46. Crunelle CL, Yegles M, van Nuijs AL, Covaci A, De Doncker M, Maudens KE, Sabbe B, Dom G, Lambert WE, Michielsen P, Neels H (2014) Hair ethyl glucuronide levels as a marker for alcohol use and abuse: a review of the current state of the art. Drug Alcohol Depend 134:1–11

    CAS  PubMed  Article  Google Scholar 

  47. Jenkins AJ, Engelhart DA (2006) Phencyclidine detection in nails. J Anal Toxicol 30:643–644

    CAS  PubMed  Article  Google Scholar 

  48. Jenkins AJ, Gubanich K (2002) Disposition of citalopram in biological specimens from postmortem cases. J Forensic Sci 47:159–164

    CAS  PubMed  Google Scholar 

  49. Al-Delaimy WK, Mahoney GN, Speizer FE, Willett WC (2002) Toenail nicotine levels as a biomarker of tobacco smoke exposure. Cancer Epidem Biomar 11:1400–1404

    CAS  Google Scholar 

  50. Stepanov I, Feuer R, Jensen J, Hatsukami D, Hecht SS (2006) Mass spectrometric quantitation of nicotine, cotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in human toenails. Cancer Epidem Biomar 15:2378–2383

    CAS  Article  Google Scholar 

  51. Stepanov I, Hecht SS, Lindgren B, Jacob P, Wilson M, Benowitz NL (2007) Relationship of human toenail nicotine, cotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol to levels of these biomarkers in plasma and urine. Cancer Epidem Biomar 16:1382–1386

    CAS  Article  Google Scholar 

  52. Al-Delaimy WK, Willett WC (2008) Measurement of tobacco smoke exposure: comparison of toenail nicotine biomarkers and self-reports. Cancer Epidem Biomar 17:1255–1261

    CAS  Article  Google Scholar 

  53. Al-Delaimy WK, Stampfer MJ, Manson JE, Willett WC (2008) Toenail nicotine levels as predictors of coronary heart disease among women. Am J Epidemiol 167:1342–1348

    PubMed  Article  Google Scholar 

  54. Schutte-Borkovec K, Heppel CW, Heling AK, Richter E (2009) Analysis of myosmine, cotinine and nicotine in human toenail, plasma and saliva. Biomarkers 14:278–284

    PubMed  Article  Google Scholar 

  55. Al-Delaimy WK, Willett WC (2011) Toenail nicotine level as a novel biomarker for lung cancer risk. Am J Epidemiol 173:822–828

    PubMed Central  PubMed  Article  Google Scholar 

  56. Hsieh SJ, Ware LB, Eisner MD, Yu L, Jacob P 3rd, Havel C, Goniewicz ML, Matthay MA, Benowitz NL, Calfee CS (2011) Biomarkers increase detection of active smoking and secondhand smoke exposure in critically ill patients. Crit Care Med 39:40–45

    PubMed Central  PubMed  Article  Google Scholar 

  57. Stepanov I, Hecht SS (2008) Detection and quantitation of N′-nitrosonornicotine in human toenails by liquid chromatography-electrospray ionization-tandem mass spectrometry. Cancer Epidem Biomar 17:945–948

    CAS  Article  Google Scholar 

  58. Stepanov I, Knezevich A, Zhang L, Watson CH, Hatsukami DK, Hecht SS (2012) Carcinogenic tobacco-specific N-nitrosamines in US cigarettes: three decades of remarkable neglect by the tobacco industry. Tob Control 21:44–48

    PubMed Central  PubMed  Article  Google Scholar 

  59. Irving RC, Dickson SJ (2007) The detection of sedatives in hair and nail samples using tandem LC-MS-MS. Forensic Sci Int 166:58–67

    CAS  PubMed  Article  Google Scholar 

  60. Chen H, Xiang P, Sun QR, Shen M (2012) Comparison of clozapine in nail and hair of psychiatric patients determined with LC-MS/MS. Yao Xue Xue Bao 47:1193–1199

    CAS  PubMed  Google Scholar 

  61. Chen H, Xiang P, Shen M (2014) Determination of clozapine in hair and nail: the role of keratinous biological materials in the identification of a bloated cadaver case. J Forensic Leg Med 22:62–67

    PubMed  Article  Google Scholar 

  62. Choi MH, Yoo YS, Chung BC (2001) Measurement of testosterone and pregnenolone in nails using gas chromatography–mass spectrometry. J Chromatogr B 754:495–501

    CAS  Article  Google Scholar 

  63. Brown HG, Perrett D (2011) Detection of doping in sport: detecting anabolic-androgenic steroids in human fingernail clippings. Med Leg J 79:67–69

    PubMed  Article  Google Scholar 

  64. Krumbiegel F, Hastedt M, Tsokos M (2014) Nails are a potential alternative matrix to hair for drug analysis in general unknown screenings by liquid-chromatography quadrupole time-of-flight mass spectrometry. Forensic Sci Med Pathol 10:496–503

    CAS  PubMed  Article  Google Scholar 

  65. Koren G, Hutson J, Gareri J (2008) Novel methods for the detection of drug and alcohol exposure during pregnancy: implications for maternal and child health. Clin Pharmacol Ther 83:631–634

    CAS  PubMed  Article  Google Scholar 

  66. Bandstra ES, Morrow CE, Mansoor E, Accornero VH (2010) Prenatal drug exposure: infant and toddler outcomes. J Addict Dis 29:245–258

    PubMed  Article  Google Scholar 

  67. Zook EG, Van Beek AL, Russell RC, Beatty ME (1980) Anatomy and physiology of the perionychium: a review of the literature and anatomic study. J Hand Surg Am 5:528–536

    CAS  PubMed  Article  Google Scholar 

  68. Gray T, Huestis M (2007) Bioanalytical procedures for monitoring in utero drug exposure. Anal Bioanal Chem 388:1455–1465

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  69. European Monitoring Centre for Drugs and Drug Addiction (2008) Sexual assaults facilitated by drugs or alcohol. http://www.emcdda.europa.eu/publications/technical-datasheets/dfsa. Accessed September 2014

  70. Le Gros Clark WE, Buxton LHD (1938) Studies in nail growth. Br J Dermatol 50:221–235

    Article  Google Scholar 

  71. Gilchrist ML (1939) The relation of finger-nail growth to nutritional status. J Anat 73:575–582

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Jones FW (1942) The principles of anatomy as seen in the hand, 2nd edn. Baillaire Tindall Cox, London

    Google Scholar 

  73. Sibinga MS (1959) Observations on growth of fingernails in health and disease. Pediatrics 24:225–233

    CAS  PubMed  Google Scholar 

  74. Orentreich N, Markofsky J, Vogelman JH (1979) The effect of aging on the rate of linear nail growth. J Invest Dermatol 73:126–130

    CAS  PubMed  Article  Google Scholar 

  75. Geyer AS, Onumah N, Uyttendaele H, Scher RK (2004) Modulation of linear nail growth to treat diseases of the nail. J Am Acad Dermatol 50:229–234

    PubMed  Article  Google Scholar 

  76. Yaemsiri S, Hou N, Slining MM, He K (2010) Growth rate of human fingernails and toenails in healthy American young adults. J Eur Acad Dermatol Venereol 24:420–423

    CAS  PubMed  Article  Google Scholar 

  77. Ropero-Miller JD, Huestis MA, Stout PR (2012) Cocaine analytes in human hair: evaluation of concentration ratios in different cocaine sources, drug-user populations and surface-contaminated specimens. J Anal Toxicol 36:390–398

    CAS  PubMed  Article  Google Scholar 

  78. Green SJ, Wilson JF (1996) The effect of hair color on the incorporation of methadone into hair in the rat. J Anal Toxicol 20:121–123

    CAS  PubMed  Article  Google Scholar 

  79. Reid RW, O’Connor FL, Deakin AG, Ivery DM, Crayton JW (1996) Cocaine and metabolites in human graying hair: pigmentary relationship. J Toxicol Clin Toxicol 34:685–690

    CAS  PubMed  Article  Google Scholar 

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Acknowledgments

PhD student Delphine Cappelle is grateful to the University of Antwerp for her scholarship. Dr. Alexander van Nuijs acknowledges the Flanders Scientific Funds for Research (FWO) for his grant. Our thanks also go to Dr. Catherine Denis who provided valuable comments to the writing of this review.

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There are no financial or other relations that could lead to a conflict of interest.

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Cappelle, D., Yegles, M., Neels, H. et al. Nail analysis for the detection of drugs of abuse and pharmaceuticals: a review. Forensic Toxicol 33, 12–36 (2015). https://doi.org/10.1007/s11419-014-0258-1

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  • DOI: https://doi.org/10.1007/s11419-014-0258-1

Keywords

  • Nail analysis
  • Drugs of abuse
  • Pharmaceuticals
  • Xenobiotics
  • Keratinized matrix
  • Pre-analytical and analytical techniques