Skip to main content
Top
Published in: Forensic Toxicology 1/2022

Open Access 01-01-2022 | Review Article

Alternative matrices in forensic toxicology: a critical review

Authors: Eduardo Geraldo de Campos, Bruno Ruiz Brandão da Costa, Fabiana Spineti dos Santos, Fernanda Monedeiro, Marcela Nogueira Rabelo Alves, Wilson José Ramos Santos Junior, Bruno Spinosa De Martinis

Published in: Forensic Toxicology | Issue 1/2022

Login to get access

Abstract

Purpose

The use of alternative matrices in toxicological analyses has been on the rise in clinical and forensic settings. Specimens alternative to blood and urine are useful in providing additional information regarding drug exposure and analytical benefits. The goal of this paper is to present a critical review on the most recent literature regarding the application of six common alternative matrices, i.e., oral fluid, hair, sweat, meconium, breast milk and vitreous humor in forensic toxicology.

Methods

The recent literature have been searched and reviewed for the characteristics, advantages and limitations of oral fluid, hair, sweat, meconium, breast milk and vitreous humor and its applications in the analysis of traditional drugs of abuse and novel psychoactive substances (NPS).

Results

This paper outlines the properties of six biological matrices that have been used in forensic analyses, as alternatives to whole blood and urine specimens. Each of this matrix has benefits in regards to sampling, extraction, detection window, typical drug levels and other aspects. However, theses matrices have also limitations such as limited incorporation of drugs (according to physical–chemical properties), impossibility to correlate the concentrations for effects, low levels of xenobiotics and ultimately the need for more sensitive analysis. For more traditional drugs of abuse (e.g., cocaine and amphetamines), there are already data available on the detection in alternative matrices. However, data on the determination of emerging drugs such as the NPS in alternative biological matrices are more limited.

Conclusions

Alternative biological fluids are important specimens in forensic toxicology. These matrices have been increasingly reported over the years, and this dynamic will probably continue in the future, especially considering their inherent advantages and the possibility to be used when blood or urine are unavailable. However, one should be aware that these matrices have limitations and particular properties, and the findings obtained from the analysis of these specimens may vary according to the type of matrix. As a potential perspective in forensic toxicology, the topic of alternative matrices will be continuously explored, especially emphasizing NPS.
Literature
4.
go back to reference Moriya F (2005) Alternative specimens. In: Suzuki O, Watanabe K (eds) Drugs and poisons in humans: handbook of practical analysis. Springer-Verlag, Berlin/Heidelberg, pp 9–15CrossRef Moriya F (2005) Alternative specimens. In: Suzuki O, Watanabe K (eds) Drugs and poisons in humans: handbook of practical analysis. Springer-Verlag, Berlin/Heidelberg, pp 9–15CrossRef
38.
go back to reference Rocchi R, Simeoni MC, Montesano C, Vannutelli G, Curini R, Sergi M, Compagnone D (2018) Analysis of new psychoactive substances in oral fluids by means of microextraction by packed sorbent followed by ultra-high-performance liquid chromatography-tandem mass spectrometry. Drug Test Anal 10:865–873. https://doi.org/10.1002/dta.2330CrossRefPubMed Rocchi R, Simeoni MC, Montesano C, Vannutelli G, Curini R, Sergi M, Compagnone D (2018) Analysis of new psychoactive substances in oral fluids by means of microextraction by packed sorbent followed by ultra-high-performance liquid chromatography-tandem mass spectrometry. Drug Test Anal 10:865–873. https://​doi.​org/​10.​1002/​dta.​2330CrossRefPubMed
39.
42.
go back to reference Tsuji M, Kanda H, Hayakawa T, Mori Y, Ito T, Hidaka T, Kakamu T, Kumagai T, Osaki Y, Kawazoe M, Sato S, Fukushima T (2017) Nicotine cut-off value in human hair as a tool to distinguish active from passive smokers: a cross-sectional study in Japanese men. Cancer Biomark 20:41–48. https://doi.org/10.3233/CBM-170004CrossRefPubMed Tsuji M, Kanda H, Hayakawa T, Mori Y, Ito T, Hidaka T, Kakamu T, Kumagai T, Osaki Y, Kawazoe M, Sato S, Fukushima T (2017) Nicotine cut-off value in human hair as a tool to distinguish active from passive smokers: a cross-sectional study in Japanese men. Cancer Biomark 20:41–48. https://​doi.​org/​10.​3233/​CBM-170004CrossRefPubMed
44.
63.
go back to reference Tzatzarakis MN, Alegakis AK, Kavvalakis MP, Vakonaki E, Stivaktakis PD, Kanaki K, Vardavas AI, Barbounis EG, Tsatsakis AM (2016) Comparative evaluation of drug deposition in hair samples collected from different anatomical body sites. J Anal Toxicol 41:214–223. https://doi.org/10.1093/jat/bkw127(open access article) CrossRef Tzatzarakis MN, Alegakis AK, Kavvalakis MP, Vakonaki E, Stivaktakis PD, Kanaki K, Vardavas AI, Barbounis EG, Tsatsakis AM (2016) Comparative evaluation of drug deposition in hair samples collected from different anatomical body sites. J Anal Toxicol 41:214–223. https://​doi.​org/​10.​1093/​jat/​bkw127(open access article) CrossRef
68.
go back to reference Kuwayama K, Miyaguchi H, Kanamori T, Tsujikawa K, Yamamuro T, Segawa H, Okada Y, Iwata YT (2021) Development of the “selective concentration” analytical method for drug-containing hair regions based on micro-segmental analysis to identify a trace amount of drug in hair: hair analysis following single-dose ingestion of midazolam. Forensic Toxicol 39:156–166. https://doi.org/10.1007/s11419-020-00553-8CrossRef Kuwayama K, Miyaguchi H, Kanamori T, Tsujikawa K, Yamamuro T, Segawa H, Okada Y, Iwata YT (2021) Development of the “selective concentration” analytical method for drug-containing hair regions based on micro-segmental analysis to identify a trace amount of drug in hair: hair analysis following single-dose ingestion of midazolam. Forensic Toxicol 39:156–166. https://​doi.​org/​10.​1007/​s11419-020-00553-8CrossRef
70.
go back to reference Kamata T, Shima N, Miki A, Matsuo E, Yamamoto T, Tsuchihashi H, Sato T, Shimma S, Katagi M (2020) High spatial-resolution matrix-assisted laser desorption/ionization-ion trap-time-of-flight tandem mass spectrometry imaging for depicting longitudinal and transverse distribution of drugs incorporated into hair. Anal Chem 92:5821–5829. https://doi.org/10.1021/acs.analchem.9b05401CrossRefPubMed Kamata T, Shima N, Miki A, Matsuo E, Yamamoto T, Tsuchihashi H, Sato T, Shimma S, Katagi M (2020) High spatial-resolution matrix-assisted laser desorption/ionization-ion trap-time-of-flight tandem mass spectrometry imaging for depicting longitudinal and transverse distribution of drugs incorporated into hair. Anal Chem 92:5821–5829. https://​doi.​org/​10.​1021/​acs.​analchem.​9b05401CrossRefPubMed
77.
go back to reference Hussain JN, Mantri N, Cohen MM (2017) Working up a good sweat—the challenges of standardising sweat collection for metabolomics analysis. Clin Biochem Rev 38:13–34 (PMID: 28798503) PubMedPubMedCentral Hussain JN, Mantri N, Cohen MM (2017) Working up a good sweat—the challenges of standardising sweat collection for metabolomics analysis. Clin Biochem Rev 38:13–34 (PMID: 28798503) PubMedPubMedCentral
98.
go back to reference Clark DA (1977) Times of first void and first stool in 500 newborns. Pediatrics 60:457–459 (PMID: 905009) CrossRef Clark DA (1977) Times of first void and first stool in 500 newborns. Pediatrics 60:457–459 (PMID: 905009) CrossRef
108.
go back to reference Concheiro M, Lendoiro E, de Castro A, Gónzalez-Colmenero E, Concheiro-Guisan A, Peñas-Silva P, Macias-Cortiña M, Cruz-Landeira A, López-Rivadulla M (2017) Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy. Drug Test Anal 9:898–904. https://doi.org/10.1002/dta.2087CrossRefPubMed Concheiro M, Lendoiro E, de Castro A, Gónzalez-Colmenero E, Concheiro-Guisan A, Peñas-Silva P, Macias-Cortiña M, Cruz-Landeira A, López-Rivadulla M (2017) Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy. Drug Test Anal 9:898–904. https://​doi.​org/​10.​1002/​dta.​2087CrossRefPubMed
111.
go back to reference Bakdash A, Burger P, Goecke TW, Fasching PA, Reulbach U, Bleich S, Hastedt M, Rothe M, Beckmann MW, Pragst F, Kornhuber J (2010) Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium from newborns for detection of alcohol abuse in a maternal health evaluation study. Anal Bioanal Chem 396:2469–2477. https://doi.org/10.1007/s00216-010-3474-5CrossRefPubMed Bakdash A, Burger P, Goecke TW, Fasching PA, Reulbach U, Bleich S, Hastedt M, Rothe M, Beckmann MW, Pragst F, Kornhuber J (2010) Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium from newborns for detection of alcohol abuse in a maternal health evaluation study. Anal Bioanal Chem 396:2469–2477. https://​doi.​org/​10.​1007/​s00216-010-3474-5CrossRefPubMed
118.
138.
go back to reference Behpour M, Nojavan S, Asadi S, Shokri A (2020) Combination of gel-electromembrane extraction with switchable hydrophilicity solvent-based homogeneous liquid-liquid microextraction followed by gas chromatography for the extraction and determination of antidepressants in human serum, breast milk and wastewater. J Chromatogr A 1621:461041. https://doi.org/10.1016/j.chroma.2020.461041CrossRefPubMed Behpour M, Nojavan S, Asadi S, Shokri A (2020) Combination of gel-electromembrane extraction with switchable hydrophilicity solvent-based homogeneous liquid-liquid microextraction followed by gas chromatography for the extraction and determination of antidepressants in human serum, breast milk and wastewater. J Chromatogr A 1621:461041. https://​doi.​org/​10.​1016/​j.​chroma.​2020.​461041CrossRefPubMed
141.
go back to reference Hale TW, Rowe HE (2017) Medications and mothers’ milk. Springer Publishing Co, New York Hale TW, Rowe HE (2017) Medications and mothers’ milk. Springer Publishing Co, New York
143.
go back to reference Tennes K, Avitable N, Blackard C, Boyles C, Hassoun B, Holmes L, Kreye M (1985) Marijuana: prenatal and postnatal exposure in the human. NIDA Res Monogr 59:48–60 (PMID: 3929132) PubMed Tennes K, Avitable N, Blackard C, Boyles C, Hassoun B, Holmes L, Kreye M (1985) Marijuana: prenatal and postnatal exposure in the human. NIDA Res Monogr 59:48–60 (PMID: 3929132) PubMed
145.
go back to reference Chasnoff IJ, Lewis DE, Squires L (1987) Cocaine intoxication in a breast-fed infant. Pediatrics 80:836–838 (PMID: 3684393) PubMed Chasnoff IJ, Lewis DE, Squires L (1987) Cocaine intoxication in a breast-fed infant. Pediatrics 80:836–838 (PMID: 3684393) PubMed
168.
go back to reference Sanches LR, Seulin SC, Leyton V, Paranhos BAPB, Pasqualucci CA, Muñaoz DR, Osselton MD, Yonamine M (2012) Determination of opiates in whole blood and vitreous humor: a study of the matrix effect and an experimental design to optimize conditions for the enzymatic hydrolysis of glucuronides. J Anal Toxicol 36:162–170. https://doi.org/10.1093/jat/bks007(open access article)CrossRefPubMed Sanches LR, Seulin SC, Leyton V, Paranhos BAPB, Pasqualucci CA, Muñaoz DR, Osselton MD, Yonamine M (2012) Determination of opiates in whole blood and vitreous humor: a study of the matrix effect and an experimental design to optimize conditions for the enzymatic hydrolysis of glucuronides. J Anal Toxicol 36:162–170. https://​doi.​org/​10.​1093/​jat/​bks007(open access article)CrossRefPubMed
169.
go back to reference Ishikawa AA, Bordin DM, de Campos EG, Blanes L, Doble P, De Martinis BS (2018) A gas chromatography–mass spectrometry method for toxicological analysis of MDA, MDEA and MDMA in vitreous humor samples from victims of car accidents. J Anal Toxicol 42:661–666. https://doi.org/10.1093/jat/bky044(open access article) CrossRefPubMed Ishikawa AA, Bordin DM, de Campos EG, Blanes L, Doble P, De Martinis BS (2018) A gas chromatography–mass spectrometry method for toxicological analysis of MDA, MDEA and MDMA in vitreous humor samples from victims of car accidents. J Anal Toxicol 42:661–666. https://​doi.​org/​10.​1093/​jat/​bky044(open access article) CrossRefPubMed
174.
go back to reference Clauwaert KM, Van Bocxlaer JF, De Letter EA, Van Calenbergh S, Lambert WE, De Leenheer AP (2000) Determination of the designer drugs 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, and 3,4-methylenedioxyamphetamine with HPLC and fluorescence detection in whole blood, serum, vitreous humor, and urine. Clin Chem 46:1968–1977. https://doi.org/10.1093/clinchem/46.12.1968(open access article)CrossRefPubMed Clauwaert KM, Van Bocxlaer JF, De Letter EA, Van Calenbergh S, Lambert WE, De Leenheer AP (2000) Determination of the designer drugs 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, and 3,4-methylenedioxyamphetamine with HPLC and fluorescence detection in whole blood, serum, vitreous humor, and urine. Clin Chem 46:1968–1977. https://​doi.​org/​10.​1093/​clinchem/​46.​12.​1968(open access article)CrossRefPubMed
180.
go back to reference dos Santos MF, Yamada A, Seulin SC, Leyton V, Pasqualucci CAG, Muñoz DR, Yonamine M (2016) Liquid-phase microextraction and gas chromatographic-mass spectrometric analysis of antidepressants in vitreous humor: study of matrix effect of human and bovine vitreous and saline solution. J Anal Toxicol 40:187–193. https://doi.org/10.1093/jat/bkv141(open access article) CrossRefPubMedPubMedCentral dos Santos MF, Yamada A, Seulin SC, Leyton V, Pasqualucci CAG, Muñoz DR, Yonamine M (2016) Liquid-phase microextraction and gas chromatographic-mass spectrometric analysis of antidepressants in vitreous humor: study of matrix effect of human and bovine vitreous and saline solution. J Anal Toxicol 40:187–193. https://​doi.​org/​10.​1093/​jat/​bkv141(open access article) CrossRefPubMedPubMedCentral
185.
go back to reference Thaulow CH, Øiestad ÅML, Rogde S, Karinen R, Brochmann GW, Andersen JM, Høiseth G, Handal M, Mørland J, Arnestad M, Øiestad EL, Strand DH, Vindenes V (2018) Metabolites of heroin in several different post-mortem matrices. J Anal Toxicol 42:311–320. https://doi.org/10.1093/jat/bky002(open access article)CrossRefPubMed Thaulow CH, Øiestad ÅML, Rogde S, Karinen R, Brochmann GW, Andersen JM, Høiseth G, Handal M, Mørland J, Arnestad M, Øiestad EL, Strand DH, Vindenes V (2018) Metabolites of heroin in several different post-mortem matrices. J Anal Toxicol 42:311–320. https://​doi.​org/​10.​1093/​jat/​bky002(open access article)CrossRefPubMed
191.
go back to reference Logan BK, Stafford DT (1990) High-performance liquid chromatography with column switching for the determination of cocaine and benzoylecgonine concentrations in vitreous humor. J Forensic Sci 35:1303–1309 (PMID: 2262767) CrossRef Logan BK, Stafford DT (1990) High-performance liquid chromatography with column switching for the determination of cocaine and benzoylecgonine concentrations in vitreous humor. J Forensic Sci 35:1303–1309 (PMID: 2262767) CrossRef
195.
go back to reference Øiestad ÅML, Karinen R, Rogde S, Nilsen S, Eldor K-BB, Brochmann G-W, Arnestad M, Øiestad EL, Peres MD, Kristoffersen L, Vindenes V (2018) Comparative study of postmortem concentrations of antidepressants in several different matrices. J Anal Toxicol 42:446–458. https://doi.org/10.1093/jat/bky030(open access article) CrossRefPubMed Øiestad ÅML, Karinen R, Rogde S, Nilsen S, Eldor K-BB, Brochmann G-W, Arnestad M, Øiestad EL, Peres MD, Kristoffersen L, Vindenes V (2018) Comparative study of postmortem concentrations of antidepressants in several different matrices. J Anal Toxicol 42:446–458. https://​doi.​org/​10.​1093/​jat/​bky030(open access article) CrossRefPubMed
200.
go back to reference Matey JM, García-Ruíz C, Montalvo G, Gómez-Soro JC, Gutierrez-Delicado D, Rodríguez-Gallardo J, Martínez MA (2020) Ultraviolet-visible and high-resolution mass spectrometry for the identification of cyclopropyl-fentanyl in the first fatal case in Spain. J Anal Toxicol 44:927–935. https://doi.org/10.1093/jat/bkaa081CrossRefPubMed Matey JM, García-Ruíz C, Montalvo G, Gómez-Soro JC, Gutierrez-Delicado D, Rodríguez-Gallardo J, Martínez MA (2020) Ultraviolet-visible and high-resolution mass spectrometry for the identification of cyclopropyl-fentanyl in the first fatal case in Spain. J Anal Toxicol 44:927–935. https://​doi.​org/​10.​1093/​jat/​bkaa081CrossRefPubMed
205.
go back to reference Sofalvi S, Schueler HE, Lavins ES, Kaspar CK, Brooker IT, Mazzola CD, Dolinak D, Gilson TP, Perch S (2017) An LC-MS-MS method for the analysis of carfentanil, 3-methylfentanyl, 2-furanyl fentanyl, acetyl fentanyl, fentanyl and norfentanyl in postmortem and impaired-driving cases. J Anal Toxicol 41:473–483. https://doi.org/10.1093/jat/bkx052(open access article)CrossRefPubMed Sofalvi S, Schueler HE, Lavins ES, Kaspar CK, Brooker IT, Mazzola CD, Dolinak D, Gilson TP, Perch S (2017) An LC-MS-MS method for the analysis of carfentanil, 3-methylfentanyl, 2-furanyl fentanyl, acetyl fentanyl, fentanyl and norfentanyl in postmortem and impaired-driving cases. J Anal Toxicol 41:473–483. https://​doi.​org/​10.​1093/​jat/​bkx052(open access article)CrossRefPubMed
216.
go back to reference Poklis JL, Devers KG, Arbefeville EF, Pearson JM, Houston E, Poklis A (2014) Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death. Forensic Sci Int 234:e14–e20. https://doi.org/10.1016/j.forsciint.2013.10.015CrossRefPubMed Poklis JL, Devers KG, Arbefeville EF, Pearson JM, Houston E, Poklis A (2014) Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death. Forensic Sci Int 234:e14–e20. https://​doi.​org/​10.​1016/​j.​forsciint.​2013.​10.​015CrossRefPubMed
Metadata
Title
Alternative matrices in forensic toxicology: a critical review
Authors
Eduardo Geraldo de Campos
Bruno Ruiz Brandão da Costa
Fabiana Spineti dos Santos
Fernanda Monedeiro
Marcela Nogueira Rabelo Alves
Wilson José Ramos Santos Junior
Bruno Spinosa De Martinis
Publication date
01-01-2022
Publisher
Springer Singapore
Published in
Forensic Toxicology / Issue 1/2022
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-021-00596-5

Other articles of this Issue 1/2022

Forensic Toxicology 1/2022 Go to the issue