The development of maintenance treatment for subjects with addictive behavior is an important public health issue. Buprenorphine, a promising new drug for the treatment of opiates addition, has been widely abused since the mid-90's. Using drug testing for buprenorphine will become an important issue. The proposed research will focus on the preparation of the reference materials of two major urinary metabolites of buprenorphine, namely, buprenorphine-3-beta-D-glucuronide and buprenorphine-3-beta-D-glucuronide, which are not commercially available. The successful development of these two compounds will make it possible during the Phase II research to prepare the deuterated analogs of these metabolites and to achieve our long-term goals such as optimization of the analytical protocols, development of an efficient immunoassay technology, development of marketing of urine controls, and preparation of these standards and internal standards in bulk quantities for commercial marketing. Two possible synthetic routes as well as an enzymatic synthesis have been proposed for the synthesis. Route 1 has been tested on small scale and proved to be workable. Route 2 starts with a cheap starting material but requires multiple synthetic steps. The enzymatic synthesis will use either uridine diphosphate glucuronosyltransferase (UDPGT) in solution or immobilized UDPGT to catalyze the reactions. These processes will evaluated based on their efficiency and feasibility. Upon completion of the synthesis, the optimum enzymatic hydrolysis conditions will be assessed using different types of glucuronidases.
The products developed in this research will be marked as reference standard materials for analytical laboratories, hospitals, and drug testing research organizations. The products will also be used for preparation of urine controls for marketing purposes, and the deuterated analogs (to be prepared during Phase II) will be marked as internal standards to other analytical laboratories.
| Nguyen, Peter T; Schmid, Cullen L; Raehal, Kirsten M et al. (2012) ?-arrestin2 regulates cannabinoid CB1 receptor signaling and adaptation in a central nervous system region-dependent manner. Biol Psychiatry 71:714-24 |
| Elsohly, Mahmoud A; Gul, Waseem; Feng, Shixia et al. (2005) Hydrolysis of conjugated metabolites of buprenorphine II. The quantitative enzymatic hydrolysis of norbuprenorphine-3-beta-D-glucuronide in human urine. J Anal Toxicol 29:570-3 |
