Abstract
A universal and robust analytical method for the determination of Δ9-tetrahydrocannabinol (THC) and two of its metabolites Δ9-(11-OH)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Δ9-carboxy-tetrahydrocannabinol (THC-COOH) in human whole blood was developed and validated for use in forensic toxicology. Protein precipitation, integrated solid phase extraction and on-line enrichment followed by high-performance liquid chromatography separation and detection with a triple quadrupole mass spectrometer were combined. The linear ranges used for the three cannabinoids were from 0.5 to 20 ng/mL for THC and 11-OH-THC and from 2.5 to 100 ng/mL for THC-COOH, therefore covering the requirements for forensic use. Correlation coefficients of 0.9980 or better were achieved for all three analytes. No relevant hydrolysis was observed for THC-COOH glucuronide with this procedure — in contrast to our previous GC-MS procedure, which obviously lead to an artificial increase of the THC-COOH concentration due to the hydrolysis of the glucuronide-conjugate occurring at high pH during the phase-transfer catalyzed methylation step.
Similar content being viewed by others
References
Labat L, Fontaine B, Delzenne C, Doublet A, Marek MC, Tellier D, Tonneau M, Lhermitte M, Frimat P (2008) For Sci Intl 174:90
Ronen A, Gershon P, Drobiner H, Rabinovich A, Bar-Hamburger R, Mechoulam R, Cassuto Y, Shinar D (2008) Accid Anal Prev 40:926
Mura P, Chatelain C, Dumestre V, Gaulier JM, Ghysel MH, Lacroix C, Kergueris MF, Lhermitte M, Moulsma M, Pepin G, Vincent F, Kintz P (2006) For Sci Intl 160:168
Ramaekers JG, Moeller MR, van Ruitenbeek P, Theunissen EL, Schneider E, Kauert G (2006) Drug Alcohol Depend 85:114
Appenzeller BMR, Schneider S, Yegles M, Maul A, Wennig R (2005) For Sci Intl 155:83
Huestis MA, Barnes A, Smith ML (2005) Clin Chem 51:2289
Ramaekers JG, Berghaus G, van Laar M, Drummer OH (2004) Drug Alcohol Depend 73:109
Drummer OH, Gerostamoulos J, Batziris H, Chu M, Caplehorn JRM, Robertson MD, Swann P (2003) For Sci Intl 134:154
Ramirez-Fernandez M, De Boeck G, Wood M, Lopez-Rivadulla M, Samyn N (2008) J Chrom B 875:465
Grauwiler SB, Scholer A, Dreweb J (2007) J Chrom B 850:515
Jung J, Kempf J, Mahler H, Weinmann W (2007) J Mass Spectrom 42:354
Nadulski T, Pragst F (2007) J Chrom B 846:78
Pizzolato TM, Lopez de Alda MJ, Barcelo D (2007) Trends Anal Chem 26:609
Quintela O, Andrenyak DM, Hoggan AM, Crouch DJ (2007) J Anal Toxicol 31:157
Teixeira H, Verstraete A, Proenca P, Corte-Real F, Monsanto P, Vieira DN (2007) For Sci Intl 170:148
Thomas A, Widmer C, Hopfgartner G, Staub C (2007) J Pharm Biomed Anal 45:495
Laloup M, Ramirez Fernandez MM, Wood M, De Boeck G, Maes V, Samyn N (2006) For Sci Intl 161:175
Maralikova B, Weinmann W (2004) J Mass Spectrom 39:526
Uhl M, Sachs H (2004) For Sci Intl 145:143
Gustafson RA, Moolchan ET, Barnes A, Levine B, Huestis MA (2003) J Chrom B 798:145
Musshoff F, Lachenmeier DW, Kroener L, Madea B (2003) For Sci Intl 133:32
Breindahl T, Andreasen K (1999) J Chrom B 732:155
Staub C (1999) J Chrom B 733:119
Milman G, Barnes AJ, Lowe RH, Huestis MA (2010) J Chrom A 1217–1513
Goodwin RS, Gustafson RA, Barnes A, Nebro W, Moolchan ET, Huestis MA (2006) Ther Drug Monit 28:545
Nadulski T, Sporkert F, Schnelle M, Stadelmann AM, Roser P, Schefter T, Pragst F (2005) J Anal Toxicol 29:782
Musshoff F, Madea B (2006) Ther Drug Monit 28:155
Abraham TT, Lowe RH, Pirnay SO, Darwin WD, Huestis MA (2007) J Anal Toxicol 31:477
Huestis MA, Scheidweiler KB, Saito T, Fortner N, Abraham T, Gustafson RA, Smith ML (2008) Forensic Sci Int 174:173
Giroud C, Ménétrey A, Augsburger M, Buclin T, Sanchez-Mazas P, Mangin P (2001) For Sci Intl 123:150
Guidance for Industry, Bioanalytical Method Validation, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM) from May 2001
Peters FT, Maurer HH (2002) Accred Qual Assur 7:441
Peters FT, Drummer OH, Musshoff F (2007) Forensic Sci Int 165:216
Skopp G, Poetsch L, Mauden M, Richter B (2002) For Sci Intl 126:17
Skopp G, Pötsch L, Mauden M, Richter B, Aderjan R, Mattern R (1999) Rechtsmedizin 10:21
Skopp G, Poetsch L (2002) Clin Chem 48:301
Weinmann W, Freisleben S, Auwärter V (2009) “1,1 ng/mL THC im Serum—§24a StVG—Einstellung des Widerspruchverfahrens“. In: Verkehrsmedizin—Neueste Erkenntnisse im gesamten Spektrum. Ed. Rolf Hennighausen, Rainer Mattern, Verlag Kirschbaum, Bonn, Germany, p. 53–55
Weinmann W, Vogt S, Goerke R, Mueller C, Bromberger A (2000) For Sci Intl 113:381
Acknowledgments
We gratefully acknowledge the contributions of Matthias Herzog, Brechbühler AG, Zürich, and Stefan Brand, Dionex AG, Olten, and Sidonia Guggisberg, Thomas Wüthrich, Nicole Ochsenbein, and Anita Iannone for their contributions.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published in the special issue Forensic Toxicology with Guest Editors Frank T. Peters, Hans H. Maurer, and Frank Musshoff.
Electronic supplementary materials
Below is the link to the electronic supplementary material.
ESM 1
(PDF 577 kb)
Rights and permissions
About this article
Cite this article
König, S., Aebi, B., Lanz, S. et al. On-line SPE LC-MS/MS for the quantification of Δ9-tetrahydrocannabinol (THC) and its two major metabolites in human peripheral blood by liquid chromatography tandem mass spectrometry. Anal Bioanal Chem 400, 9–16 (2011). https://doi.org/10.1007/s00216-011-4708-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-011-4708-x