Identification of a major metabolite of nortriptyline in human urine

✍ Scribed by A. De Leenheer; A. Heyndrickx

• Publisher: John Wiley and Sons
• Year: 1971
• Tongue: English
• Weight: 361 KB
• Volume: 60
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600600925

✦ Synopsis

Urine samples taken from a person who ingested nortriptyline.HC1 (4 X 25 mg. daily) were extracted by a two-phase procedure with ether. A first screening by UV spectrophotometry showed the presence of compound(s) with basic character but different from free nortriptyline. The TLC separation of aliquots of extracts revealed traces of free nortriptyline, three minor metabolites, and a more polar major metabolite. These results were confirmed by GLC, which was performed on the acetylated extracts using two different columns. Elucidation of the structure of the major metabolite was attempted in two ways. A I-hr. treatment of the extract with 1 N HC1 at 100' caused a @-elimination and transformed the compound to a polyene structure demonstrated by the typical UV spectral shift. A microcollection technique for trapping GLC effluents was developed to obtain the acetylated derivative of the metabolite in a highly purified form. From the trapped compound, a micro-IR and low-and high-resolution mass spectra were recorded; these permitted a thorough interpretation. These experiments indicated that 10-hydroxynortriptyline is excreted in human urine as a major metabolite from nortriptyline. Desmethylnortriptyline was not detected in the urine.