Sensitive method for the quantitation of nortriptyline and 10-hydroxynortriptyline in human plasma by capillary gas chromatography with electron-capture detection

• Published in: Journal of chromatography Vol. 573; no. 1; pp. 141 - 145
• Main Authors: Anliker, S.L., Hamilton, M., Bopp, R.J., Goldberg, M.J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 03.01.1992; Elsevier
• Subjects: Biological and medical sciences; Chromatography, Gas; Electrochemistry; Humans; Indicators and Reagents; Medical sciences; Neuropharmacology; Nortriptyline - analogs & derivatives; Nortriptyline - blood; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Antidepressant agent; Tricyclic compound; Metabolite; Quantitative analysis; Blood plasma
• ISSN: 0378-4347
• DOI: 10.1016/0378-4347(92)80487-B

A method for the determination of nortriptyline and 10-hydroxynortriptyline concentrations in human plasma by capillary gas chromatography with electron-capture detection is described. The procedure requires 1.0 ml of plasma and uses maprotiline as an internal standard. The compounds are extracted from alkalinized plasma with hexane—2-butanol (98:2) and back-extracted into hydrochloric acid. The acid solution is then made basic and the compounds are re-extracted into n-butyl chloride. The extract is evaporated to dryness, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography on a fused-silica capillary column coated with phenylmethyl silicone. The calibration curves for nortriptyline and 10-hydroxynortriptyline are linear in the ranges 3–40 and 7–90 μg/l, respectively, with coefficients of variation for within-day and between-day precision of less than 12%. The quantitation limits for nortriptyline and 10-hydroxynortriptyline are 1 and 3 μg/l, respectively. This procedure was used to analyze more than 1400 samples following sub-therapeutic doses of nortriptyline in human subjects. The assay was sufficiently sensitive for use in pharmacokinetic analysis.