title: Accurate identification and quantification of 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid in urine drug testing: evaluation of a direct high efficiency liquid chromatographic-mass spectrometric method.
abstract: A direct liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for measurement of urinary Delta(9)-tetrahydrocannabinol carboxylic acid (THCA) was developed. The method involved dilution of the urine sample with water containing (2)H(9)-deuterated analogue as internal standard, hydrolysis with ammonia, reversed phase chromatography using a Waters ultra-performance liquid chromatography (UPLC) equipment with gradient elution, negative electrospray ionization, and monitoring of two product ions in selected reaction monitoring mode. The measuring range was 2-1000 ng/mL for THCA, and the intra- and inter-assay imprecision, expressed as the coefficient of variation, was below 5%. Influence from urine matrix on ionization efficiency was noted in infusion experiments, but was compensated for by the internal standard. Comparison with established gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry methods in authentic patient samples demonstrated accuracy in both qualitative and quantitative results. A small difference in mean ratios (~15%) may be explained by the use of different hydrolysis procedures between methods. In conclusion, the high efficiency LC-MS/MS method was capable of accurately identify and quantify THCA in urine with a capacity of 14 samples per hour.
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Stephanson
authors.forename: Martin
authors.initials: M
authors.lastname: Josefsson
authors.forename: Robert
authors.initials: R
authors.lastname: Kronstrand
authors.forename: Olof
authors.initials: O
authors.lastname: Beck
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol