title: Partition coefficient, blood to plasma ratio, protein binding and short-term stability of 11-nor-Delta(9)-carboxy tetrahydrocannabinol glucuronide.
abstract: 11-Nor-Delta(9)-carboxy tetrahydrocannabinol glucuronide (THCCOOglu) is a major metabolite of tetrahydrocannabinol in blood. Despite its mass spectrometric identification already in 1980, further physicochemical data of THCCOOglu have not been established. Therefore, the octanol/buffer partition coefficient P and the blood to plasma ratio b/p for THCCOOglu concentrations of 100 and 500ng/ml were investigated. Protein binding of the glucuronide was established from spiked albumin solutions at a level of 250ng/ml as well as from authentic samples. The data were compared to those of 11-nor-Delta(9)-carboxy tetrahydrocannabinol (THCCOOH). In addition, the short-term stability of THCCOOglu in plasma at different storage temperatures was studied. Analysis was performed by LC/MS/MS. The glucuronide partition coefficient P (mean: 17.4 and 18.0 for 100 and 500ng/ml, respectively) was unexpectedly lipophilic at pH 7.4. Its blood to plasma ratios averaged 0.62 and 0.68 at 100 and 500ng/ml, respectively. THCCOOglu was highly reversibly bound to albumin (mean: 97%), and the mean fraction bound did not differ from that determined from authentic samples. THCCOOglu degraded even at a storage temperature of 4 degrees C and THCCOOH was identified as a major decomposition product.
authors.affiliation: Institute of Legal Medicine, University of Heidelberg, Vossstr. 2, D-69115, Heidelberg, Germany. gisela_skopp@med.uni-heidelberg.de
authors.forename: Gisela
authors.initials: G
authors.lastname: Skopp
authors.forename: Lucia
authors.initials: L
authors.lastname: Pötsch
authors.forename: Martin
authors.initials: M
authors.lastname: Mauden
authors.forename: Barbara
authors.initials: B
authors.lastname: Richter
mesh_terms: D001800:Blood Specimen Collection; D013759:Dronabinol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood; D004355:Drug Stability; D005554:Forensic Medicine; D020719:Glucuronides / Q000032:analysis* / Q000097:blood; D006801:Humans; D013058:Mass Spectrometry; D011485:Protein Binding
chemical_list: D020719:Glucuronides; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol