The differentiation between legal and illegal opiate product use through the detection of marker compounds in urine is one of the most important subjects in forensic toxicology. Thebaine, an opium alkaloid, can be detected by gas chromatography-mass spectrometry (GC-MS) and has been suggested as a good marker of poppy seed use in differentiation from that of illicit heroin. In the present study, thebaine was targeted as a urinary marker of opium use because it is a major constituent of opium. Although thebaine lacks the conventional functional group, it was found to form a trimethylsilyl (TMS) derivative. This has made it possible to simultaneously detect thebaine together with morphine and codeine in the same urine sample to confirm opium use, thus saving time and cost of analysis while using less material. The TMS derivatization was found to enhance the stability and chromatographic properties of thebaine and to increase the sensitivity of its detection about 50-fold in comparison with that of the underivatized compound. Using the present method, thebaine was analyzed for a number of actual urine samples obtained from users of opium, illicit heroin, or codeine preparation. The results showed that thebaine is a useful opium-use marker subject to its oral administration.
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Al-Amri AM, Smith RM, El-Haj BM, Juma’a MAH (2004) GC-MS detection and characterization of reticuline as opium use marker. Forensic Sci Int 142:61–69
Al-Amri AM, Smith RM, El-Haj BM (2005) The GC-MS detection and characterization of neopine resulting from opium use and codeine metabolism and its potential as an opiate-product-use marker. Anal Bioanal Chem 382:839–835
Al-Amri AM (2004) Marker compounds in urine for opiate product use. Doctoral thesis, Department of Chemistry, Loughborough University, UK
Yeh SY, Gorodetzky CW, McQuinn RL (1976) Urinary excretion of heroin and its metabolites in man. J Pharmacol Exp Ther 196:249–256
Brenneisen R, Hasler F, Wursch D (2002) Acetylcodeine as a urinary marker to differentiate the use of street heroin and pharmaceutical heroin. J Anal Toxicol 26:561–566
Sweetman SC (ed) (2002) Martindale the complete drug reference, 33rd edn. Pharmaceutical, London, p 1333
Bogusz MJ, Maier RD, Erkens M, Kohls U (2001) Detection of non-prescription heroin markers in urine with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. J Anal Toxicol 25:431–438
Mclachlan-Troup N, Taylor GW, Trathen BC (2001) Diamorphine treatment for opiate dependence: putative markers of contaminant heroin misuse. Addict Biol 6:223–231
El-Haj BM, Al-Amri AM, Ali HS (2007) GC-MS detection and tentative characterization of two noscapine metabolites and their potential as markers for opium and illicit heroin use. Forensic Toxicol 25:22–29 DOI 10.1007/s11419-007-0023-9
Tsunoda N, Yoshimura H (1979) Metabolic fate of noscapine, II. Isolation and identification of novel metabolites produced by C-C bond cleavage. Xenobiotica 9:181–187
Tsunoda N, Yoshimura H (1981) Metabolic fate of noscapine III: further studies on identification and determination of the metabolites. Xenobiotica 11:23–32
ElSohly HN, Stanford DF, Jones AB, ElSohly MA, Snyder H, Pedersen C (1988) Gas chromatography/mass spectrometric analysis of morphine and codeine in human urine of poppy seed eaters. J Forensic Sci 33:347–355
Cassella G, Wu AHB, Shaw BR, Hill DW (1997) The analysis of thebaine in urine for the detection of poppy seed consumption. J Anal Toxicol 21:376–383
Lewis RJ, Johnson RD, Hattrup RA (2005) Simultaneous analysis of thebaine, 6-MAM and six abused opiates in postmortem fluids and tissues using Zymark automated solidphase extraction and gas chromatography-mass spectrometry. J Chromatogr B 822:137–145
Meadway C, George S, Braithwaite R (1998) Opiate concentration following the ingestion of poppy seed products—evidence for ‘the poppy seed defense’. Forensic Sci Int 96:29–38
Johnson RD, Lewis J, Hattrup RA (2005) Poppy seed consumption or opiate use: the determination of thebaine and opiates of abuse in postmortem fluids and tissues. DOT/FAA/AM-05/11, Office of Aerospace Medicine, Washington DC, 20591. www.cami.jccbi.gov/aam-400a/Abstracts/2005/FULL20%TEXT/0511.pdf. Cited 7 December 2006
Schiff PL Jr (2002) Opium and its alkaloids. Am J Pharm Educ 66:186–194
Chen W, Wu H, Bernard D, Metcalf MD, Deschamps JR, Flippen L, Mackerell AD Jr, Coop A (2003) Rearrangement of 5-trimethylsilylthebaine on treatment with L-selectride: an efficient synthesis of (+)-bractazonine. J Org Chem 68:1929–1932
Kushnir MM, Crockett DK, Nelson G, Urry FM (1999) Comparison of four derivatizing reagents for 6-acetylmorphine GC-MS analysis. J Anal Toxicol 23:262–269
Penton Z (2002) Derivatization of drugs prior to GC-MS analysis. Varian Product Information Bulletin, Application Note number MSP 2218, Palo Alto, CA
Yinon J (1995) Forensic applications of mass spectrometry. CRC, London, p 33
Regis Technologies (2000) GC derivatization. www.registech.com/gc/gcderrev.pdf. Cited 21 December 2006
Little JL (1999) Artifacts in trimethylsilyl derivatization reactions and ways to avoid them. J Chromatogr A 844:1–22
Chen W, Parrish DA, Deschamps JR, Coop A (2005) Functionalization of the 6,14-bridge of the orvinols 1. Preparation of Diels-Alder reaction of 7-phenylsilylthebaine. Helv Chim Acta 88:822–829
Soine WH (1986) Clandestine drug synthesis. Med Res Rev 6:41–74
Fehn J, Megges G (1985) Detection of O 6-monoacetyl morphine in urine samples by GC-MS as evidence for heroin use. J Anal Toxicol 9:2–7
Cone EJ, Welch P, Mitchell JM, Paul D (1991) Forensic drug testing for opiates: I. Detection of 6-acetylmorphine in urine as an indicator of recent heroin exposure; drug and assay considerations and detection times. J Anal Toxicol 15:1–7
Westermeyer J (1987) Cultural patterns of drug and alcohol use: an analysis of host and agent in the cultural environment. UNODC Bull Narcotics 2:11–27
Wu F-F, Dobberstein RH (1977) Quantitative determination of thebaine in Papaver bracteatum by high-pressure liquid chromatography. J Chromatogr 140:65–70
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El-Haj, B.M., Al-Amri, A.M., Ali, H.S. et al. GC-MS detection and characterization of thebaine as a urinary marker of opium use. Forensic Toxicol 25, 62 (2007). https://doi.org/10.1007/s11419-007-0028-4
- Urinary marker
- Opium use
- Oral route
- Trimethylsilyl derivatization