Quantitative Determination of 2-Hydroxy-3-Methoxy-6β-Naltrexol (HMN), Naltrexone, and 6β-Naltrexol in Human Plasma, Red Blood Cells, Saliva, and Urine by Gas Liquid Chromatography

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Abstract
Two gas liquid chromatographic methods differing mainly in sensitivity are described for the quantitative determination of 2-hydroxy-3-methoxy-6β-naltrexol (HMN), a minor metabolite of naltrexone (NT), in human body-fluids. The methods also incorporate simultaneous determinations of naltrexone and its major human metabolite, 6β-naltrexol (β-OL), in urine, serum (or plasma), red blood cells (RBC), and saliva. Flame ionization detection of the bis-(trimethylsylll) trifluoroacetamide (BSTFA) derivatives provided sufficient sensitivity for quantitation of the bases in urine. However, lower levels in serum, RBC and saliva necessitated the use of more sensitive electron capture detection of the pentafluoropropionate (PFPA) derivatives of the bases. Because HMN and 6β-naltrexol PFPA derivatives have nearly identical gas chromatographic retention times, their separation was achieved by differential extraction, based on their different partition characteristics between aqueous and organic solvents in the plasma of 4 subjects, 15 and 24 hrs. after 2×200 mg NT doses, the relative percentages were 23.1% HMN, 3.4% NT and 73.5% β-OL. In urine samples collected at the same time as the blood samples the relative percentages were 14.4% HMN, 9.0% NT and 76.6% β-OL. The nonpolar nature of HMN and the greater polarity of β-OL may have influenced their differential distribution into RBCs and saliva. In the RBCs, 96.1% HMN and no significant amount of β-OL was found. In saliva, 92.3% of β-OL and no HMN was found.