Rapid Quantification of Urinary 11-nor- 9-Tetrahydrocannabinol-9-Carboxylic Acid Using Fast Gas Chromatography-Mass Spectrometry

Abstract

Human urine specimens that were determined to be presumptively positive for metabolites of delta9-tetrahydrocannabinol by immunoassay screening were assayed using a novel fast gas chromatography-mass spectrometry (FGC-MS) analytical method to determine whether this method would improve the efficiency of specimen processing without diminishing the reliability of metabolite identification and quantification. Urine specimens were spiked with deuterated internal standard, subjected to solid-phase extraction, and derivatized using tetramethylammonium hydroxide and iodomethane. The methyl ester/methyl ether derivatives were identified and quantified using both a traditional GC-MS method and the newly developed FGC-MS method. The FGC-MS method was demonstrated to be linear between 3.8 and 1500 ng/mL 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (11-nor-delta-THC-COOH). The intrarun precision of 15 replicates of a 15 ng/mL control and the interrun precision of 161 sets of 7, 15, and 60 ng/mL controls were acceptable (coefficients of variation < 5.5%). The FGC-MS method was demonstrated to be specific for identifying 11-nor-delta9-THC-COOH and none of 43 tested substances interfered with identification and quantification of 11-nor-delta9-THC-COOH. Excellent data concordance (R2 > 0.993) was found for two specimen sets assayed using both methods. The FGC-MS method, when compared with a traditional GC-MS method, reduces total assay time by approximately 40% with no decrease in data quality.