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Arzneimittelforschung. 1979;29(1):158-61.
Gas chromatographic determination of amitriptyline, nortriptyline and perphenazine in plasma of schizophrenic patients after administration of the combination of amitriptyline with perphenazine.

Cooper S, Albert JM, Dugal R, Bertrand M, Elie R.

A specific and sensitive gas-chromatographic technique using a common extraction procedure for the quantitative determination of amitriptyline, endogenous nortriptyline and perphenazine in plasma of schizophrenic patients receiving therapeutic doses of a combination of amitriptyline and perphenazine (Etrafon) has been developed. The lower limits of detection are 20 ng/ml for amitriptyline, 1 ng/ml for nortriptyline and 5 ng/ml for perphenazine. Amitriptyline is estimated with a flame ionization detector. Nortriptyline is quantitated using an electron capture detector after converting it to its heptafluorobutyryl derivative by reaction with the appropriate anhydride. Perphenazine is also determined using an electron capture detector after forming its stable, trimethylsilyl derivative by reaction with N,O-bis-(trimethylsilyl)-acetamide. In individual patients, the steady-state plasma levels ranged from 44 to 215 ng/ml for amitriptyline, from 49 to 270 ng/ml for nortriptyline and from less than 5 to 20 ng/ml for perphenazine. Steady-state plasma levels data on amitriptyline, nortriptyline and perphenazine in 23 patients treated with Etrafon are presented.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=582110&dopt=Abstract




Clin Pharmacol Ther. 1979 Jun;25(6):844-56.
A method for the determination of amitriptyline and its metabolites nortriptyline, 10-hydroxyamitriptyline, and 10-hydroxynortriptyline in human plasma using stable isotope dilution and gas chromatography-chemical ionization mass spectrometry (GC-CIMS).

Garland WA, Muccino RR, Min BH, Cupano J, Fann WE.

A gas chromatography--mass spectrometry (GC-MS) method has been developed to measure amitriptyline and its metabolites nortriptyline, 10-hydroxyamitriptyline, and 10-hydroxynortriptyline in human plasma. Deuterated analogs of each compound were synthesized as internal standards. Isobutane was used as both gas chromatography (GC) carrier gas and chemical ionization (CI) reagent gas. In order to obtain compounds with satisfactory GC and mass spectrometry (MS) properties, the two alcohol metabolites were dehydrated without loss of label during sample preparation. Selective ion monitoring of the MH+ ions of the protio- and deuterio- compounds gave ion ratios which were converted to plasma concentrations using standard curves. For amitriptyline and nortriptyline, which are assayed using multiple deuterated analogs as internal standards, the curves are straight lines. For 10-hydroxyamitriptyline and 10-hydroxynortriptyline, which are assayed using monodeuterated analogs as internal standards, the curves are nonlinear and are analyzed using an iterative computer procedure. Assay sensitivity is 0.5 ng/ml for amitriptyline, nortriptyline, and 10-hydroxyamitriptyline and 1 ng/ml for 10-hydroxynortriptyline. Assay precision and accuracy in terms of percent error are both less than 5%. Following oral administration of a single 75-mg dose of amitriptyline to two subjects, the mean plasma levels of amitriptyline, nortriptyline, 10-hydroxyamitriptyline, conjugated 10-hydroxyamitriptyline, 10-hydroxynortriptyline, and conjugated 10-hydroxynortriptyline were 36, 8, 10, 66, 16, and 46 ng/ml, respectively, at 2 hr after dosing and 3, 4, 0.5, 1, 6, and 17 ng/ml, respectively, at 72 hr after dosing. Analyses of plasma samples from 12 subjects who had been receiving 50 mg amitriptyline therapy three times a day for an average +/- SD of 32 +/- 5 days gave a mean concentration of 81 +/- 40 ng/ml for amitriptyline, 71 +/- 57 ng/ml for nortriptyline, 12 +/- 5 ng/ml for 10-hydroxyamitriptyline, 91 +/- 30 ng/ml for conjugated 10-hydroxyamitriptyline, 82 +/- 27 ng/ml for 10-hydroxynortriptyline, and 176 +/- 64 ng/ml for conjugated 10-hydroxynortriptyline.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=376209&dopt=Abstract




Brain Res. 1982 Mar 4;235(1):192-7.
Modulation of rat brain alpha 2- and beta-adrenergic receptor sensitivity following long-term treatment with antidepressants.

Asakura M, Tsukamoto T, Hasegawa K.

After 7 days of treatment with a variety of antidepressant drugs (desipramine, imipramine, clomipramine, nortriptyline, nialamide), both an increase in alpha 2-receptor density and a decrease in beta-receptor density were observed in the cerebral cortex but not limbic forebrain. However, mianserin caused a marked increase in alpha 2-receptors without any change in beta-receptors. Nisoxetine did not produce any change in these two adrenergic receptors. It is suggested that intrasynaptic norepinephrine is important but that, in addition, other factors may be involved in the increase in alpha 2-receptors induced by antidepressant drugs.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6329413&dopt=Abstract













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