| Popis: |
Two gas liquid chromatographic methods differing mainly in sensitivity are described for the quantitative determination of naltrexone (NT) and its metabolites in human biofluids. Flame ionization detection of the N,O-bis-(trimethylsilyl) trifluoroacetamide (BSTFA) derivatives provided sufficient separation and sensitivity for quantitative of the bases in urine. However, the thousand times lower levels in serum, red blood cells (RBC) and saliva necessitated the use of more sensitive electron capture detection methods of the pentafluoro derivatives of NT and its metabolites. The 2-hydroxy-3-methoxy-6 beta-naltrexol (HMN) and 6 beta-naltrexol (beta-OL) pentafluoro derivatives had nearly identical gas liquid chromatographic retention times in a number of stationary liquid phases. Thus, their separation had to be achieved prior to chromatography. Differential extraction was based on the different partition characteristics of HMN and 6 beta-naltrexol between aqueous and organic solvents. Applicability of the methods was tested using the biofluids of four subjects taking 2 x 200 mg naltrexone per day chronically. Blood, saliva and urine samples were collected at the same time (prior to drug administration), which was 16 and 24 hours after the doses. In the plasma the relative percentages of the bases were 73.5 beta-OL; 23.1 HMN and 3.4 NT. The same in the urine were 76.6 beta-OL, 14.4 HMN and 9.0 NT. The lipophilic nature of HMN and the hydrophilic property of beta-OL may have influenced their distribution into RBC and saliva. In the RBC 96.1% HMN and only trace amounts of beta-OL distributed and in saliva 92.3% of beta-OL and no HMN was found; the difference in both cases was made up by naltrexone to 100%. |
