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)

Clinical Pharmacology and Therapeutics
W A GarlandW E Fann

Abstract

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 i...Continue Reading

Citations

Jul 1, 1984·Journal of Toxicology. Clinical Toxicology·P K SonsallaC Collins
Nov 24, 2004·Drug Metabolism Reviews·Ursula Breyer-Pfaff
Jun 1, 1980·Environmental Health Perspectives·W A Garland, B J Miwa
Jul 1, 1980·Acta Pharmacologica Et Toxicologica·J HyttelB Fjalland
Jul 1, 1986·Journal of Clinical Pharmacology·D A Schoeller
May 10, 1985·Journal of Chromatography·T R Norman, K P Maguire

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