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Published in: Forensic Toxicology 2/2014

01-08-2014 | Original Article

Analysis of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in urine samples by hollow fiber-liquid phase microextraction and gas chromatography–mass spectrometry in consideration of measurement uncertainty

Authors: Sarah Carobini Werner de Souza Eller, Luma Gonçalves Flaiban, Beatriz Aparecida Passos Bismara Paranhos, José Luiz da Costa, Felipe Rebello Lourenço, Mauricio Yonamine

Published in: Forensic Toxicology | Issue 2/2014

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Abstract

Marijuana abuse can be detected by means of toxicological analysis of the most important metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in urine samples. The aim of this study is the establishment of the detailed procedure for analysis of THC-COOH in urine by combination of hollow fiber-liquid phase microextraction (HF-LPME) and gas chromatography–mass spectrometry (GC–MS). The conditions of hydrolysis and extraction were optimized. The method was shown to be very simple and rapid, and a low amount of organic solvent was necessary for extraction. The limit of detection was 1.5 ng/ml. The calibration curves were linear over the specified range (2.0–170 ng/ml; r 2  > 0.99). The main sources of uncertainty were found to be analyte concentration, accuracy, method precision and sample volume. The effect of the analyte concentration on the overall combined uncertainty was most significant. The developed method was successfully applied to a human urine standard reference material at two levels of concentration. The obtained relative combined uncertainty was 8 %, which can be considered acceptable according to international guidelines. The present method seems very useful in clinical and forensic toxicology, because of its simplicity, rapidness and inexpensiveness.
Literature
1.
go back to reference Papoutsis I, Nikolaou P, Dona A, Pistos C, Stefanidou M, Spiliopoulou C, Athanaselis S (2012) A validated GC–MS method for the determination of Δ9-tetrahydrocannabinol and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in bile samples. Forensic Toxicol 30:51–58CrossRef Papoutsis I, Nikolaou P, Dona A, Pistos C, Stefanidou M, Spiliopoulou C, Athanaselis S (2012) A validated GC–MS method for the determination of Δ9-tetrahydrocannabinol and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in bile samples. Forensic Toxicol 30:51–58CrossRef
2.
go back to reference Fabritius M, Staub C, Mangin P, Giroud C (2013) Analysis of cannabinoids in oral fluid by liquid chromatography–tandem mass spectrometry. Forensic Toxicol 31:151–163CrossRef Fabritius M, Staub C, Mangin P, Giroud C (2013) Analysis of cannabinoids in oral fluid by liquid chromatography–tandem mass spectrometry. Forensic Toxicol 31:151–163CrossRef
3.
go back to reference Namera A, Saito T, Miyazaki S, Ohta S, Oikawa H, Torikoshi A, Shiraishi H, Nagao M (2013) Sequential extraction of amphetamines, opiates, and 11-nor- Δ9-tetrahydrocannabinol-9-carboxylic acid from a limited volume of urine using a monolithic silica spin column coupled with gas chromatography–mass spectrometry. Forensic Toxicol 31:312–321CrossRef Namera A, Saito T, Miyazaki S, Ohta S, Oikawa H, Torikoshi A, Shiraishi H, Nagao M (2013) Sequential extraction of amphetamines, opiates, and 11-nor- Δ9-tetrahydrocannabinol-9-carboxylic acid from a limited volume of urine using a monolithic silica spin column coupled with gas chromatography–mass spectrometry. Forensic Toxicol 31:312–321CrossRef
4.
go back to reference Kikura-Hanajiri R, Uchiyama N, Kawamura M, Goda Y (2013) Changes in the prevalence of synthetic cannabinoids and cathinone derivatives in Japan until early 2012. Forensic Toxicol 31:44–53CrossRef Kikura-Hanajiri R, Uchiyama N, Kawamura M, Goda Y (2013) Changes in the prevalence of synthetic cannabinoids and cathinone derivatives in Japan until early 2012. Forensic Toxicol 31:44–53CrossRef
5.
go back to reference Scheidweiler KB, Desrosiers NA, Huestis MA (2012) Simultaneous quantification of free and glucuronidated cannabinoids in human urine by liquid chromatography tandem mass spectrometry. Clin Chim Acta 413:1839–1847PubMedCentralPubMedCrossRef Scheidweiler KB, Desrosiers NA, Huestis MA (2012) Simultaneous quantification of free and glucuronidated cannabinoids in human urine by liquid chromatography tandem mass spectrometry. Clin Chim Acta 413:1839–1847PubMedCentralPubMedCrossRef
6.
go back to reference Felli M, Martello S, Chiarotti M (2011) LC–MS–MS method for simultaneous determination of THCCOOH and THCCOOH-glucuronide in urine: application to workplace confirmation tests. Forensic Sci Int 204:67–73PubMedCrossRef Felli M, Martello S, Chiarotti M (2011) LC–MS–MS method for simultaneous determination of THCCOOH and THCCOOH-glucuronide in urine: application to workplace confirmation tests. Forensic Sci Int 204:67–73PubMedCrossRef
7.
go back to reference Lacroix C, Saussereau E (2012) Fast liquid chromatography/tandem mass spectrometry determination of cannabinoids in micro volume blood samples after dabsyl derivatization. J Chromatogr B 905:85–95CrossRef Lacroix C, Saussereau E (2012) Fast liquid chromatography/tandem mass spectrometry determination of cannabinoids in micro volume blood samples after dabsyl derivatization. J Chromatogr B 905:85–95CrossRef
8.
go back to reference Stephanson N, Josefsson M, Kronstrand R, Beck O (2008) Accurate identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine drug testing: evaluation of a direct high efficiency liquid chromatographic–mass spectrometric method. J Chromatogr B 871:101–108CrossRef Stephanson N, Josefsson M, Kronstrand R, Beck O (2008) Accurate identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine drug testing: evaluation of a direct high efficiency liquid chromatographic–mass spectrometric method. J Chromatogr B 871:101–108CrossRef
9.
go back to reference Racamonde KE, Villaverde-de-Sáa E, Rodil R, Quintana JB, Cela R (2012) Determination of Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in water samples by solid-phase microextraction with on-fiber derivatization and gas chromatography-mass spectrometry. J Chromatogr A 1245:167–174PubMedCrossRef Racamonde KE, Villaverde-de-Sáa E, Rodil R, Quintana JB, Cela R (2012) Determination of Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in water samples by solid-phase microextraction with on-fiber derivatization and gas chromatography-mass spectrometry. J Chromatogr A 1245:167–174PubMedCrossRef
10.
go back to reference De Brabanter N, Gansbeke WV, Hooghe F, Van Eenoo P (2013) Fast quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCA) using microwave-accelerated derivatisation and gas chromatography–triple quadrupole mass spectrometry. Forensic Sci Int 224:90–95PubMedCrossRef De Brabanter N, Gansbeke WV, Hooghe F, Van Eenoo P (2013) Fast quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCA) using microwave-accelerated derivatisation and gas chromatography–triple quadrupole mass spectrometry. Forensic Sci Int 224:90–95PubMedCrossRef
11.
go back to reference Jagerdeo E, Montgomery MA, Karas RP, Sibum M (2010) A fast method for screening and/or quantitation of tetrahydrocannabinol and metabolites in urine by automated SPE/LC/MS/MS. Anal Bional Chem 398:329–338CrossRef Jagerdeo E, Montgomery MA, Karas RP, Sibum M (2010) A fast method for screening and/or quantitation of tetrahydrocannabinol and metabolites in urine by automated SPE/LC/MS/MS. Anal Bional Chem 398:329–338CrossRef
13.
go back to reference Zanchetti G, Floris I, Piccinotti A, Tameni S, Polettini A (2012) Rapid and robust confirmation and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in urine by column switching LC-MS-MS analysis. J Mass Spectrom 47:124–130PubMedCrossRef Zanchetti G, Floris I, Piccinotti A, Tameni S, Polettini A (2012) Rapid and robust confirmation and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in urine by column switching LC-MS-MS analysis. J Mass Spectrom 47:124–130PubMedCrossRef
14.
go back to reference Chebbah C, Pozo OJ, Deventer K, Eenoo PV, Delbeke FT (2010) Direct quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine by liquid chromatography/tandem mass spectrometry in relation to doping control analysis. Rapid Commun Mass Spectrom 24:1133–1141PubMedCrossRef Chebbah C, Pozo OJ, Deventer K, Eenoo PV, Delbeke FT (2010) Direct quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine by liquid chromatography/tandem mass spectrometry in relation to doping control analysis. Rapid Commun Mass Spectrom 24:1133–1141PubMedCrossRef
15.
go back to reference Fernández MMR, Wille SMR, Samyn N, Wood M, Lopes-Rivadulla M, De Boeck G (2009) On-line solid-phase extraction combined with chromatography-tandem mass spectrometry for high throughput analysis of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol acid in urine. J Chromatogr B 877:2153–2157CrossRef Fernández MMR, Wille SMR, Samyn N, Wood M, Lopes-Rivadulla M, De Boeck G (2009) On-line solid-phase extraction combined with chromatography-tandem mass spectrometry for high throughput analysis of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol acid in urine. J Chromatogr B 877:2153–2157CrossRef
16.
go back to reference Robandt PV, Klette KL, Sibum M (2009) Automated solid-phase extraction-liquid chromatography-tandem mass spectrometry analysis of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in human urine specimens: application to a high-throughput urine analysis laboratory. J Anal Toxicol 33:456–460PubMedCrossRef Robandt PV, Klette KL, Sibum M (2009) Automated solid-phase extraction-liquid chromatography-tandem mass spectrometry analysis of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in human urine specimens: application to a high-throughput urine analysis laboratory. J Anal Toxicol 33:456–460PubMedCrossRef
17.
go back to reference Chericoni S, Battistini I, Dugheri S, Pacenti M, Giusiani M (2011) Novel method for simultaneous aqueous in situ derivatization of THC and THC-COOH in human urine samples: validation and application to real samples. J Anal Toxicol 35:193–198PubMedCrossRef Chericoni S, Battistini I, Dugheri S, Pacenti M, Giusiani M (2011) Novel method for simultaneous aqueous in situ derivatization of THC and THC-COOH in human urine samples: validation and application to real samples. J Anal Toxicol 35:193–198PubMedCrossRef
18.
go back to reference Fu S, Lewis J (2008) Novel automated extraction method for quantitative analysis of urinary 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). J Anal Toxicol 32:292–297PubMedCrossRef Fu S, Lewis J (2008) Novel automated extraction method for quantitative analysis of urinary 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). J Anal Toxicol 32:292–297PubMedCrossRef
19.
go back to reference Abraham TT, Lowe RH, Pirnay SO, Darwin WD, Huestis MA (2007) Determination of Δ9-tetrahydrocannabinol, 1-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in human urine following tandem enzyme-alkaline hydrolysis. J Anal Toxicol 31:477–485PubMedCentralPubMedCrossRef Abraham TT, Lowe RH, Pirnay SO, Darwin WD, Huestis MA (2007) Determination of Δ9-tetrahydrocannabinol, 1-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in human urine following tandem enzyme-alkaline hydrolysis. J Anal Toxicol 31:477–485PubMedCentralPubMedCrossRef
20.
go back to reference Kumazawa T, Hasegawa C, Lee X-P, Sato K (2010) New and unique methods of solid-phase extraction for use before instrumental analysis of xenobiotics in human specimens. Forensic Toxicol 28:61–68CrossRef Kumazawa T, Hasegawa C, Lee X-P, Sato K (2010) New and unique methods of solid-phase extraction for use before instrumental analysis of xenobiotics in human specimens. Forensic Toxicol 28:61–68CrossRef
21.
go back to reference Pantaleão LN, Paranhos BAPB, Yonamine M (2007) Hollow-fiber liquid-phase microextraction of amphetamine-type stimulants in human hair samples. J Chromatogr A 1254:1–7CrossRef Pantaleão LN, Paranhos BAPB, Yonamine M (2007) Hollow-fiber liquid-phase microextraction of amphetamine-type stimulants in human hair samples. J Chromatogr A 1254:1–7CrossRef
22.
go back to reference Barroso M, Moreno I, Fonseca B, Queiroz JA, Gallardo E (2012) Role of microextraction sampling procedures in forensic toxicology. Bioanalysis 4:1805–1826PubMedCrossRef Barroso M, Moreno I, Fonseca B, Queiroz JA, Gallardo E (2012) Role of microextraction sampling procedures in forensic toxicology. Bioanalysis 4:1805–1826PubMedCrossRef
23.
go back to reference Menck RA, de Oliveira CDR, de Lima DS, Goes LE, Leyton V, Pasqualucci CA, Muñoz DR, Yonamine M (2013) Hollow fiber–liquid phase microextraction of barbiturates in liver samples. Forensic Toxicol 31:31–36CrossRef Menck RA, de Oliveira CDR, de Lima DS, Goes LE, Leyton V, Pasqualucci CA, Muñoz DR, Yonamine M (2013) Hollow fiber–liquid phase microextraction of barbiturates in liver samples. Forensic Toxicol 31:31–36CrossRef
24.
go back to reference dos Santos MF, Ferri CC, Seulin SC, Leyton V, Pasqualucci CAG, Muñoz DR, Yonamine M (2014) Determination of antidepressants in whole blood using hollow-fiber liquid-phase microextraction and gas chromatography-mass spectrometry. Forensic Toxicol. doi:10.1007/s11419-014-0226-9 dos Santos MF, Ferri CC, Seulin SC, Leyton V, Pasqualucci CAG, Muñoz DR, Yonamine M (2014) Determination of antidepressants in whole blood using hollow-fiber liquid-phase microextraction and gas chromatography-mass spectrometry. Forensic Toxicol. doi:10.​1007/​s11419-014-0226-9
25.
go back to reference Lee J, Lee H, Rasmussen K, Pedersen-Bjergaard S (2008) Environmental and bioanalytical applications of hollow fiber membrane liquid-phase microextraction: a review. Anal Chim Acta 624:253–268PubMedCrossRef Lee J, Lee H, Rasmussen K, Pedersen-Bjergaard S (2008) Environmental and bioanalytical applications of hollow fiber membrane liquid-phase microextraction: a review. Anal Chim Acta 624:253–268PubMedCrossRef
26.
go back to reference Gullberg RG (2012) Estimating the measurement uncertainty in forensic blood alcohol analysis. J Anal Toxicol 36:153–161PubMedCrossRef Gullberg RG (2012) Estimating the measurement uncertainty in forensic blood alcohol analysis. J Anal Toxicol 36:153–161PubMedCrossRef
27.
go back to reference Sklerov JH, Couper FJ (2011) Calculation and verification of blood ethanol measurement uncertainty for headspace gas chromatography. J Anal Toxicol 35:402–410PubMedCrossRef Sklerov JH, Couper FJ (2011) Calculation and verification of blood ethanol measurement uncertainty for headspace gas chromatography. J Anal Toxicol 35:402–410PubMedCrossRef
28.
go back to reference Lee S, Choi H, Kim E, Choi H, Chung H, Chung KH (2010) Estimation of the measurement uncertainty by the bottom-up approach for the determination of methamphetamine and amphetamine in urine. J Anal Toxicol 34:222–228PubMedCrossRef Lee S, Choi H, Kim E, Choi H, Chung H, Chung KH (2010) Estimation of the measurement uncertainty by the bottom-up approach for the determination of methamphetamine and amphetamine in urine. J Anal Toxicol 34:222–228PubMedCrossRef
31.
go back to reference Peters FT, Maurer HH (2002) Bioanalytical method validation and its implications for forensic and clinical toxicology—a review. Accred Qual Assur 7:441–449CrossRef Peters FT, Maurer HH (2002) Bioanalytical method validation and its implications for forensic and clinical toxicology—a review. Accred Qual Assur 7:441–449CrossRef
32.
35.
go back to reference Moon J, Kim JY, Moon MH, Chung BC, In MK, Choi MH (2008) Validated gas chromatographic–mass spectrometric analysis of urinary cannabinoids purified with a calcium-hardened cyclodextrin polymer. J Chromatogr A 1204:87–92PubMedCrossRef Moon J, Kim JY, Moon MH, Chung BC, In MK, Choi MH (2008) Validated gas chromatographic–mass spectrometric analysis of urinary cannabinoids purified with a calcium-hardened cyclodextrin polymer. J Chromatogr A 1204:87–92PubMedCrossRef
36.
go back to reference Weinmann W, Goerner M, Vogt S, Goerke R, Pollak S (2001) Fast confirmation of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in urine by LC/MS/MS using negative atmospheric-pressure chemical ionisation (APCI). Forensic Sci Int 121:103–107PubMedCrossRef Weinmann W, Goerner M, Vogt S, Goerke R, Pollak S (2001) Fast confirmation of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in urine by LC/MS/MS using negative atmospheric-pressure chemical ionisation (APCI). Forensic Sci Int 121:103–107PubMedCrossRef
37.
go back to reference Kim SY, Kim JY, Kwon W, In MK, Kim YE, Paeng K (2013) Method development for simultaneous determination of amphetamine type stimulants and cannabinoids in urine using GC–MS. Microchem J 110:326–333CrossRef Kim SY, Kim JY, Kwon W, In MK, Kim YE, Paeng K (2013) Method development for simultaneous determination of amphetamine type stimulants and cannabinoids in urine using GC–MS. Microchem J 110:326–333CrossRef
38.
go back to reference Kramer KE, Andrews ARJ (2001) Screening method for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine using hollow fiber membrane solvent microextraction with in-tube derivatization. J Chromatogr B 760:27–36CrossRef Kramer KE, Andrews ARJ (2001) Screening method for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine using hollow fiber membrane solvent microextraction with in-tube derivatization. J Chromatogr B 760:27–36CrossRef
39.
go back to reference Moffat AC, Osselton MD, Widdop B, Watts J (2011) Clarke’s analysis of drugs and poisons. Pharmaceutical Press, London Moffat AC, Osselton MD, Widdop B, Watts J (2011) Clarke’s analysis of drugs and poisons. Pharmaceutical Press, London
40.
go back to reference Pedersen-Bjergaard S, Rasmussen KE (2008) Liquid-phase microextraction with porous hollow fibers, a miniaturized and highly flexible format for liquid–liquid extraction. J Chromatogr A 1184:132–142PubMedCrossRef Pedersen-Bjergaard S, Rasmussen KE (2008) Liquid-phase microextraction with porous hollow fibers, a miniaturized and highly flexible format for liquid–liquid extraction. J Chromatogr A 1184:132–142PubMedCrossRef
Metadata
Title
Analysis of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in urine samples by hollow fiber-liquid phase microextraction and gas chromatography–mass spectrometry in consideration of measurement uncertainty
Authors
Sarah Carobini Werner de Souza Eller
Luma Gonçalves Flaiban
Beatriz Aparecida Passos Bismara Paranhos
José Luiz da Costa
Felipe Rebello Lourenço
Mauricio Yonamine
Publication date
01-08-2014
Publisher
Springer Japan
Published in
Forensic Toxicology / Issue 2/2014
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-014-0239-4

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