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Published in: Forensic Toxicology 1/2015

01-01-2015 | Original Article

Simultaneous determination of prescription drugs, cocaine, aldicarb and metabolites in larvae from decomposed corpses by LC–MS–MS after solid–liquid extraction with low temperature partitioning

Authors: Jéssica de Aguiar França, Marianna Brandão, Fernando Fabriz Sodré, Eloisa Dutra Caldas

Published in: Forensic Toxicology | Issue 1/2015

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Abstract

The determination of toxic substances in insect larvae collected from corpses in an advanced state of putrefaction can help to elucidate the causa mortis in forensic cases. In this study, an analytical method for the simultaneous determination of six prescription drugs, cocaine and its metabolite benzoylecgonine, and aldicarb and its sulfone and sulfoxide metabolites in larvae was developed and validated. The method involved a solid–liquid extraction with low temperature partitioning, and determination by a liquid chromatography–mass spectrometry (LC–MS–MS) method. Significant matrix effects were observed for most analytes, indicating the need to use analytical curves in pre-extracted fortified matrices. The limits of quantification ranged from 1 to 40 ng/g, with precision between 2.83 and 16.9 %. The validated method was used to analyze 28 actual larval samples collected from corpses at the Forensic Medical Institute between 2009 and 2012 in the Federal District, Brazil. At least one substance was present in 11 samples. Benzoylecgonine and diazepam were found in four samples each, followed by cocaine (three samples), carbamazepine (two samples) and amitriptyline (one sample). The method proved to be simple, fast and of low cost, and can be used by forensic laboratories as a complementary tool to elucidate intoxication-related deaths where usual toxicological matrices are not available.
Literature
1.
go back to reference Wananukul W, Sriapha C, Tongpoo A, Sadabthammarak U, Wongvisawakorn S, Kaojarern S (2007) Human poisoning in Thailand: the Ramathibodi Poison Center’s experience (2001–2004). Clin Toxicol 45:582–588CrossRef Wananukul W, Sriapha C, Tongpoo A, Sadabthammarak U, Wongvisawakorn S, Kaojarern S (2007) Human poisoning in Thailand: the Ramathibodi Poison Center’s experience (2001–2004). Clin Toxicol 45:582–588CrossRef
2.
go back to reference Bentur Y, Lurie Y, Cahana A, Lavon O, Bloom-Krasik A, Kovler N, Gurevych B, Raikhlin-Eisenkraft B (2008) Poisoning in Israel: annual report of the Israel Poison Information Center, 2007. Isr Med Assoc J 10:749–756PubMed Bentur Y, Lurie Y, Cahana A, Lavon O, Bloom-Krasik A, Kovler N, Gurevych B, Raikhlin-Eisenkraft B (2008) Poisoning in Israel: annual report of the Israel Poison Information Center, 2007. Isr Med Assoc J 10:749–756PubMed
3.
go back to reference Mowry JB, Spyker DA, Cantilena LR, Bailey JE, Ford M (2013) 2012 Annual report of the American Association of Poison Control Centers’ national poison data system (NPDS): 30th annual report. Clin Toxicol 51:949–1229CrossRef Mowry JB, Spyker DA, Cantilena LR, Bailey JE, Ford M (2013) 2012 Annual report of the American Association of Poison Control Centers’ national poison data system (NPDS): 30th annual report. Clin Toxicol 51:949–1229CrossRef
4.
go back to reference Veale DJH, Wium CA, Muller GJ (2013) Toxicovigilance I: a survey of acute poisonings in South Africa based on Tygerberg Poison Information Centre data. South Afr Med J 103:293–297 Veale DJH, Wium CA, Muller GJ (2013) Toxicovigilance I: a survey of acute poisonings in South Africa based on Tygerberg Poison Information Centre data. South Afr Med J 103:293–297
6.
go back to reference Gunnell D, Eddleston M, Phillips MR, Konradsen F (2007) The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health 7:357–371PubMedCentralPubMedCrossRef Gunnell D, Eddleston M, Phillips MR, Konradsen F (2007) The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health 7:357–371PubMedCentralPubMedCrossRef
7.
go back to reference Beyer JC, Enos WF, Stajić M (1980) Drug identification through analysis of maggots. J Forensic Sci 25:411–412PubMed Beyer JC, Enos WF, Stajić M (1980) Drug identification through analysis of maggots. J Forensic Sci 25:411–412PubMed
8.
go back to reference Campobasso CP, Gherardi M, Caligara M, Sironi L, Introna F (2004) Drug analysis in blowfly larvae and in human tissues: a comparative study. Int J Legal Med 118:210–214PubMedCrossRef Campobasso CP, Gherardi M, Caligara M, Sironi L, Introna F (2004) Drug analysis in blowfly larvae and in human tissues: a comparative study. Int J Legal Med 118:210–214PubMedCrossRef
9.
go back to reference Gosselin M, Ramirez Fernandez MDM, Wille SMR, Samyn N, De Boeck G, Bourel B (2010) Quantification of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in third instar larvae of Lucilia sericata (Diptera: Calliphoridae) using liquid chromatography-tandem mass spectrometry. J Anal Toxicol 34:374–380PubMedCrossRef Gosselin M, Ramirez Fernandez MDM, Wille SMR, Samyn N, De Boeck G, Bourel B (2010) Quantification of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in third instar larvae of Lucilia sericata (Diptera: Calliphoridae) using liquid chromatography-tandem mass spectrometry. J Anal Toxicol 34:374–380PubMedCrossRef
10.
go back to reference Gagliano-Candela R, Aventaggiato L (2001) The detection of toxic substances in entomological specimens. Int J Legal Med 114:197–203PubMedCrossRef Gagliano-Candela R, Aventaggiato L (2001) The detection of toxic substances in entomological specimens. Int J Legal Med 114:197–203PubMedCrossRef
11.
go back to reference Tracqui A, Keyser-Tracqui C, Kintz P, Ludes B (2004) Entomotoxicology for the forensic toxicologist: much ado about nothing? Int J Legal Med 118:194–196PubMedCrossRef Tracqui A, Keyser-Tracqui C, Kintz P, Ludes B (2004) Entomotoxicology for the forensic toxicologist: much ado about nothing? Int J Legal Med 118:194–196PubMedCrossRef
12.
go back to reference Bortoletto ME, Bochner R (1999) Drug impact on human poisoning in Brazil. Cad Saúde Pública 15:859–869PubMedCrossRef Bortoletto ME, Bochner R (1999) Drug impact on human poisoning in Brazil. Cad Saúde Pública 15:859–869PubMedCrossRef
13.
go back to reference Campelo ELC, Caldas ED (2010) Postmortem data related to drug and toxic substance use in the Federal District, Brazil, from 2006 to 2008. Forensic Sci Int 200:136–140PubMedCrossRef Campelo ELC, Caldas ED (2010) Postmortem data related to drug and toxic substance use in the Federal District, Brazil, from 2006 to 2008. Forensic Sci Int 200:136–140PubMedCrossRef
14.
go back to reference Pietracci E, Bermejo A-M, Álvarez I, Cabarcos P, Balduini W, Tabernero M-J (2013) Simultaneous determination of new generation antidepressants in plasma by gas chromatography-mass spectrometry. Forensic Toxicol 31:124–132CrossRef Pietracci E, Bermejo A-M, Álvarez I, Cabarcos P, Balduini W, Tabernero M-J (2013) Simultaneous determination of new generation antidepressants in plasma by gas chromatography-mass spectrometry. Forensic Toxicol 31:124–132CrossRef
15.
go back to reference Iwakura K, Ogawa T, Hattori H, Iwai M, Suzuki O, Nakagawa T (2014) Simultaneous and sensitive analysis of fourth-generation antidepressants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Forensic Toxicol 32:30–38CrossRef Iwakura K, Ogawa T, Hattori H, Iwai M, Suzuki O, Nakagawa T (2014) Simultaneous and sensitive analysis of fourth-generation antidepressants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Forensic Toxicol 32:30–38CrossRef
17.
go back to reference Mack KA, Centers for Disease Control and Prevention (CDC) (2013) Drug-induced deaths—United States, 1999–2010. MMWR Surveill Summ 62 (Suppl 3):161–163 Mack KA, Centers for Disease Control and Prevention (CDC) (2013) Drug-induced deaths—United States, 1999–2010. MMWR Surveill Summ 62 (Suppl 3):161–163
18.
go back to reference Liu S, Zhou L, Yan L, Zhang J, Han J (2014) Analysis of epidemiological characteristics of acute pesticide poisoning during. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 32:425–428PubMed Liu S, Zhou L, Yan L, Zhang J, Han J (2014) Analysis of epidemiological characteristics of acute pesticide poisoning during. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 32:425–428PubMed
19.
go back to reference Knipe DW, Metcalfe C, Fernando R, Pearson M, Konradsen F, Eddleston M, Gunnell D (2014) Suicide in Sri Lanka 1975–2012: age, period and cohort analysis of police and hospital data. BMC Public Health 14:839–851PubMedCentralPubMedCrossRef Knipe DW, Metcalfe C, Fernando R, Pearson M, Konradsen F, Eddleston M, Gunnell D (2014) Suicide in Sri Lanka 1975–2012: age, period and cohort analysis of police and hospital data. BMC Public Health 14:839–851PubMedCentralPubMedCrossRef
20.
go back to reference Rebelo FM, Caldas ED, Heliodoro VO, Rebelo RM (2011) Intoxicação por agrotóxicos no Distrito Federal, Brasil, de 2004 a 2007—análise da notificação ao Centro de Informação e Assistência Toxicológica. Ciênc Saúde Colet 16:3493–3502CrossRef Rebelo FM, Caldas ED, Heliodoro VO, Rebelo RM (2011) Intoxicação por agrotóxicos no Distrito Federal, Brasil, de 2004 a 2007—análise da notificação ao Centro de Informação e Assistência Toxicológica. Ciênc Saúde Colet 16:3493–3502CrossRef
21.
go back to reference Bucaretchi F, Prado CC, Branco MM, Soubhia P, Metta GM, Mello SM, de Capitani EM, Lanaro R, Hyslop S, Costa JL, Fernandes LCR, Vieira RJ (2012) Poisoning by illegal rodenticides containing acetylcholinesterase inhibitors (chumbinho): a prospective case series. Clin Toxicol 50:44–51CrossRef Bucaretchi F, Prado CC, Branco MM, Soubhia P, Metta GM, Mello SM, de Capitani EM, Lanaro R, Hyslop S, Costa JL, Fernandes LCR, Vieira RJ (2012) Poisoning by illegal rodenticides containing acetylcholinesterase inhibitors (chumbinho): a prospective case series. Clin Toxicol 50:44–51CrossRef
22.
go back to reference Definis-Gojanović M, Sutlović D, Britvić D, Kokan B (2007) Drug analysis in necrophagous flies and human tissues. Arh Hig Rada Toksikol 58:313–316PubMed Definis-Gojanović M, Sutlović D, Britvić D, Kokan B (2007) Drug analysis in necrophagous flies and human tissues. Arh Hig Rada Toksikol 58:313–316PubMed
23.
go back to reference Kintz P, Tracqui A, Mangin P (1990) Toxicology and fly larvae on a putrefied cadaver. J Forensic Sci Soc 30:243–246PubMedCrossRef Kintz P, Tracqui A, Mangin P (1990) Toxicology and fly larvae on a putrefied cadaver. J Forensic Sci Soc 30:243–246PubMedCrossRef
24.
go back to reference Manhoff DT, Hood I, Caputo F, Perry J, Rosen S, Mirchandani HG (1991) Cocaine in decomposed human remains. J Forensic Sci 36:1732–1735PubMed Manhoff DT, Hood I, Caputo F, Perry J, Rosen S, Mirchandani HG (1991) Cocaine in decomposed human remains. J Forensic Sci 36:1732–1735PubMed
25.
go back to reference Nolte KB, Pinder RD, Lord WD (1992) Insect larvae used to detect cocaine poisoning in a decomposed body. J Forensic Sci 37:1179–1185PubMed Nolte KB, Pinder RD, Lord WD (1992) Insect larvae used to detect cocaine poisoning in a decomposed body. J Forensic Sci 37:1179–1185PubMed
26.
go back to reference Gunatilake K, Goff ML (1989) Detection of organophosphate poisoning in a putrefying body by analyzing arthropod larvae. J Forensic Sci 34:714–716PubMed Gunatilake K, Goff ML (1989) Detection of organophosphate poisoning in a putrefying body by analyzing arthropod larvae. J Forensic Sci 34:714–716PubMed
27.
go back to reference Wood M, Laloup M, Pien K, Samyn N, Morris M, Maes RAA, de Bruijn EA, Maes EA, De Boeck G (2003) Development of a rapid and sensitive method for the quantitation of benzodiazepines in Calliphora vicina larvae and puparia by LC–MS-MS. J Anal Toxicol 27:505–512PubMedCrossRef Wood M, Laloup M, Pien K, Samyn N, Morris M, Maes RAA, de Bruijn EA, Maes EA, De Boeck G (2003) Development of a rapid and sensitive method for the quantitation of benzodiazepines in Calliphora vicina larvae and puparia by LC–MS-MS. J Anal Toxicol 27:505–512PubMedCrossRef
28.
go back to reference Peters FT (2006) Method validation using LC-MS. In: Polettini A (ed) Applications of liquid chromatography–mass spectrometry in toxicology. Pharmaceutical Press, London Peters FT (2006) Method validation using LC-MS. In: Polettini A (ed) Applications of liquid chromatography–mass spectrometry in toxicology. Pharmaceutical Press, London
29.
30.
go back to reference Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC–MS/MS. Anal Chem 75:3019–3030PubMedCrossRef Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC–MS/MS. Anal Chem 75:3019–3030PubMedCrossRef
31.
go back to reference Almeida AM, Castel-Branco MM, Falcão AC (2002) Linear regression for calibration lines revisited: weighting schemes for bioanalytical methods. J Chromatogr B 774:215–222CrossRef Almeida AM, Castel-Branco MM, Falcão AC (2002) Linear regression for calibration lines revisited: weighting schemes for bioanalytical methods. J Chromatogr B 774:215–222CrossRef
32.
go back to reference AOAC International (2012) Standard method performance requirements (SMPR) guidelines (appendix F). The official methods of analysis of AOAC International. AOAC International, Rockville, pp 1–19 AOAC International (2012) Standard method performance requirements (SMPR) guidelines (appendix F). The official methods of analysis of AOAC International. AOAC International, Rockville, pp 1–19
33.
go back to reference Rubensam G, Barreto F, Hoff RB, Pizzolato TM (2013) Determination of avermectin and milbemycin residues in bovine muscle by liquid chromatography-tandem mass spectrometry and fluorescence detection using solvent extraction and low temperature cleanup. Food Control 29:55–60CrossRef Rubensam G, Barreto F, Hoff RB, Pizzolato TM (2013) Determination of avermectin and milbemycin residues in bovine muscle by liquid chromatography-tandem mass spectrometry and fluorescence detection using solvent extraction and low temperature cleanup. Food Control 29:55–60CrossRef
34.
go back to reference Magalhães EJ, de Queiroz MELR, Penido MLO, Paiva MAR, Teodoro JAR, Augusti R, Nascentes CC (2013) Determination of cocaine in postmortem human liver exposed to overdose. Application of an innovative and efficient extraction/clean up procedure and gas chromatography–mass spectrometry analysis. J Chromatogr A 1309:15–21PubMedCrossRef Magalhães EJ, de Queiroz MELR, Penido MLO, Paiva MAR, Teodoro JAR, Augusti R, Nascentes CC (2013) Determination of cocaine in postmortem human liver exposed to overdose. Application of an innovative and efficient extraction/clean up procedure and gas chromatography–mass spectrometry analysis. J Chromatogr A 1309:15–21PubMedCrossRef
35.
go back to reference de Pinho GP, Neves AA, de Queiroz MELR, Silvério FO (2010) Pesticide determination in tomatoes by solid–liquid extraction with purification at low temperature and gas chromatography. Food Chem 121:251–256CrossRef de Pinho GP, Neves AA, de Queiroz MELR, Silvério FO (2010) Pesticide determination in tomatoes by solid–liquid extraction with purification at low temperature and gas chromatography. Food Chem 121:251–256CrossRef
36.
go back to reference Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, McKay G, Miller KJ, Patnaik RN, Powell ML, Tonelli A, Viswanathan CT, Yacobi A (2000) Bioanalytical method validation—a revisit with a decade of progress. Pharm Res 17:1551–1557PubMedCrossRef Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, McKay G, Miller KJ, Patnaik RN, Powell ML, Tonelli A, Viswanathan CT, Yacobi A (2000) Bioanalytical method validation—a revisit with a decade of progress. Pharm Res 17:1551–1557PubMedCrossRef
37.
go back to reference González O, Blanco ME, Iriarte G, Bartolomé L, Maguregui MI, Alonso RM (2014) Bioanalytical chromatographic method validation according to current regulations, with a special focus on the non-well defined parameters limit of quantification, robustness and matrix effect. J Chromatogr A 1353:10–27PubMedCrossRef González O, Blanco ME, Iriarte G, Bartolomé L, Maguregui MI, Alonso RM (2014) Bioanalytical chromatographic method validation according to current regulations, with a special focus on the non-well defined parameters limit of quantification, robustness and matrix effect. J Chromatogr A 1353:10–27PubMedCrossRef
38.
go back to reference Taylor PJ (2005) Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography–electrospray–tandem mass spectrometry. Clin Biochem 38:328–334PubMedCrossRef Taylor PJ (2005) Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography–electrospray–tandem mass spectrometry. Clin Biochem 38:328–334PubMedCrossRef
39.
go back to reference Zancanaro I, Limberger RP, Bohel PO, dos Santos MK, de Boni RB, Pechansky F, Caldas ED (2012) Prescription and illicit psychoactive drugs in oral fluid—LC–MS/MS method development and analysis of samples from Brazilian drivers. Forensic Sci Int 223:208–216PubMedCrossRef Zancanaro I, Limberger RP, Bohel PO, dos Santos MK, de Boni RB, Pechansky F, Caldas ED (2012) Prescription and illicit psychoactive drugs in oral fluid—LC–MS/MS method development and analysis of samples from Brazilian drivers. Forensic Sci Int 223:208–216PubMedCrossRef
40.
go back to reference Bonfiglio R, King RC, Olah TV, Merkle K (1999) The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds. Rapid Commun Mass Spectrom 13:1175–1185PubMedCrossRef Bonfiglio R, King RC, Olah TV, Merkle K (1999) The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds. Rapid Commun Mass Spectrom 13:1175–1185PubMedCrossRef
41.
go back to reference Kharbouche H, Augsburger M, Cherix D, Sporkert F, Giroud C, Wyss C, Champod C, Mangin P (2008) Codeine accumulation and elimination in larvae, pupae, and imago of the blowfly Lucilia sericata and effects on its development. Int J Legal Med 122:205–211PubMedCrossRef Kharbouche H, Augsburger M, Cherix D, Sporkert F, Giroud C, Wyss C, Champod C, Mangin P (2008) Codeine accumulation and elimination in larvae, pupae, and imago of the blowfly Lucilia sericata and effects on its development. Int J Legal Med 122:205–211PubMedCrossRef
42.
go back to reference Liu X, Shi Y, Wang H, Zhang R (2009) Determination of malathion levels and its effect on the development of Chrysomya megacephala (Fabricius) in South China. Forensic Sci Int 192:14–18PubMedCrossRef Liu X, Shi Y, Wang H, Zhang R (2009) Determination of malathion levels and its effect on the development of Chrysomya megacephala (Fabricius) in South China. Forensic Sci Int 192:14–18PubMedCrossRef
43.
go back to reference Bushby SK, Thomas N, Priemel PA, Coulter CV, Rades T, Kieser JA (2012) Determination of methylphenidate in Calliphorid larvae by liquid-liquid extraction and liquid chromatography mass spectrometry—forensic entomotoxicology using an in vivo rat brain model. J Pharm Biomed Anal 70:456–461PubMedCrossRef Bushby SK, Thomas N, Priemel PA, Coulter CV, Rades T, Kieser JA (2012) Determination of methylphenidate in Calliphorid larvae by liquid-liquid extraction and liquid chromatography mass spectrometry—forensic entomotoxicology using an in vivo rat brain model. J Pharm Biomed Anal 70:456–461PubMedCrossRef
44.
go back to reference Wolff M, Zapata Y, Morales G, Benecke M (2006) Deteccion y cuantificacion de Propoxur enlasucesion de insectos de importancia medico-legal. Rev Colomb Entomol 32:159–164 Wolff M, Zapata Y, Morales G, Benecke M (2006) Deteccion y cuantificacion de Propoxur enlasucesion de insectos de importancia medico-legal. Rev Colomb Entomol 32:159–164
45.
go back to reference Hédouin V, Bourel B, Martin-Bouyer L, Bécart A, Tournel G, Deveaux M, Gosset D (1999) Morphine perfused rabbits: a tool for experiments in forensic entomotoxicology. J Forensic Sci 44:347–350PubMed Hédouin V, Bourel B, Martin-Bouyer L, Bécart A, Tournel G, Deveaux M, Gosset D (1999) Morphine perfused rabbits: a tool for experiments in forensic entomotoxicology. J Forensic Sci 44:347–350PubMed
46.
47.
go back to reference Miller M, Lord W, Lee Goff M, Donnelly B (1994) Isolation of amitriptyline and nortriptyline from fly puparia (Phoridae) and beetle exuviae (Dermestidae) associated with mummified human remains. J Forensic Sci 39:1305–1313 Miller M, Lord W, Lee Goff M, Donnelly B (1994) Isolation of amitriptyline and nortriptyline from fly puparia (Phoridae) and beetle exuviae (Dermestidae) associated with mummified human remains. J Forensic Sci 39:1305–1313
Metadata
Title
Simultaneous determination of prescription drugs, cocaine, aldicarb and metabolites in larvae from decomposed corpses by LC–MS–MS after solid–liquid extraction with low temperature partitioning
Authors
Jéssica de Aguiar França
Marianna Brandão
Fernando Fabriz Sodré
Eloisa Dutra Caldas
Publication date
01-01-2015
Publisher
Springer Japan
Published in
Forensic Toxicology / Issue 1/2015
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-014-0255-4

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