TABLE 1

Concentrations of naltrexone and 6β-naltrexol in plasma and brain tissue after i.p. injection in mice

The two compounds were extracted from plasma or brain tissue homogenates and measured by liquid chromatography/tandem mass spectrometry, using atmospheric pressure chemical ionization/positive ionization. Nalbuphine served as the internal standard. The method was sensitive to ∼1 ng/ml (g) (3-4 nM). 6β-Naltrexol was detectable in plasma but not brain tissue after the naltrexone dose (1.9 ng/ml and 1.7 ng/ml after 10 and 60 min, respectively). In contrast, no naltrexone was detectable after administration of 6β-naltrexol. The concentrations of two compounds in each row of the table represent the injected parent drug only. Data are mean ± S.D., n = 3.


Injection

Plasma Concentration at Time after Injection (min)

Brain Concentration at Time after Injection (min)
10
60
10
60
ng/ml ng/g
Naltrexone, 1 mg/kg 54 ± 16 4 ± 1 69 ± 20 9 ± 1
6β-Naltrexol, 1 mg/kg 61 ± 7 24 ± 28 7 ± 6 9 ± 1
6β-Naltrexol, 10 mg/kg
857 ± 122
75 ± 25
89 ± 6
74 ± 14