title: Fast and sensitive LC-MS/MS assay for quantification of nortriptyline and its active metabolites E- and Z-10-hydroxynortriptyline in human plasma.
abstract: BACKGROUND
  A fast and sensitive validated assay for nortriptyline, E-10-hydroxynortriptyline and Z-10-hydroxynortriptyline in plasma following a single oral dose of nortriptyline 25 mg was needed to support a clinical study.
  
  
  RESULTS
  Plasma samples were prepared by protein precipitation, separated on a C18 column with a mobile phase consisting of 0.1% formic acid in an acetonitrile gradient over 6 min and detected by ESI in the positive mode and MS/MS. Mean recoveries of at least 90% were achieved. The LLOQ was 0.2 ng/ml for nortriptyline and 0.5 ng/ml for the metabolites. The standard curve was linear within LLOQ to 40 ng/ml (r(2) ≥ 0.997), precision was under 7.1% coefficient of variance (<16% at LLOQ) and accuracy was 92-114%.
  
  
  CONCLUSIONS
  A fast and sensitive assay for nortriptyline, E- and Z-10-hydroxynortriptyline in plasma was developed and validated. It has been applied successfully to a clinical study.
authors.affiliation: Clinical Pharmacology, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand.
authors.forename: Gitte
authors.initials: G
authors.lastname: Bonke
authors.forename: Berit P
authors.initials: BP
authors.lastname: Jensen
mesh_terms: D000928:Antidepressive Agents / Q000097:blood / Q000378:metabolism; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D009661:Nortriptyline / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; C013567:10-hydroxynortriptyline; D009661:Nortriptyline