HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY FOR THE QUANTIFICATION OF NORTRIPTYLINE AND 10-HYDROXYNORTRIPTYLINE IN PLASMA

A highly sensitive and selective method for the quantification of nort riptyline and its major 10-hydroxy metabolite in plasma is described. The method is based on liquid-liquid extraction in combination with ac id dehydration of the 10-hydroxy metabolite to the less polar 10,11-de hydronortriptyline. Deuterium labelled internal standards ([H-2(4)]NT and [H-2(3)]10-OH-NT) were used and the compounds were separated by re versed-phase HPLC and detected using atmospheric pressure chemical ion isation and mass spectrometry. The limit of quantification was 0.8 ng/ ml for both compounds. A 1-ml volume of plasma was used for analysis i n the concentration range 0.8-32 ng/ml. The within- and between-day co efficients of variation were 11% in the low, 1.6 ng/ml range, and 7% a t 8 ng ml/ml. Using this method it was possible to quantify plasma con centrations for 168 h following a single oral dose of 25 mg of nortrip tyline with good accuracy and precision. (C) 1998 Elsevier Science B.V . All rights reserved.