scholarly journals A fast screening method for tricyclic antidepressants and their urinary metabolites by FAB-tandem mass spectrometry

1997 ◽  
Vol 13 (3) ◽  
pp. 213-226 ◽  
Author(s):  
M. Schäfer ◽  
H. Budzikiewicz ◽  
H. Brzezinka ◽  
M. Schifferdecker

A screening method for tricyclic antidepressants (TCA) and their urinary metabolites by FAB tandem mass spectrometry (FAB MS/MS) is presented. The collision induced dissociation (CID) behavior of pure dibenzocycloheptadienes (amitriptyline1, nortriptyline2), dibenzoxepines (doxepine3, dosulepine4), dibenzazepines (imipramine5, desipramine6, trimipramine7) and the iminostilbene derivative opipramol8is described and used for the specific determination of these tricyclics by MS/MS.For the screening procedure a methanolic extract of the urine sample is passed through a XAD-2 column and the eluate is examined without further purification after evaporation of the solvent. Identification of the TCA is achieved by constant neutral loss (CNL) scans for 173 u, 195 u and 193 u and subsequent daughter ion spectra of the molecular ions [M+H]+. Glucuronide conjugate metabolites of the tricyclic antidepressants1,2,3,6,8could be identified by CNL-scans (176 u) and the assignments were confirmed by daughter ion mass spectra. A urine sample of a fatal1,2,8overdose and samples of three patients under therapeutic dosage with1,3or6are presented as examples for application.

2001 ◽  
Vol 73 (2) ◽  
pp. 170-176 ◽  
Author(s):  
Andreas Schlosser ◽  
Ruediger Pipkorn ◽  
Dirk Bossemeyer ◽  
Wolf D. Lehmann

2000 ◽  
Vol 46 (4) ◽  
pp. 445-452 ◽  
Author(s):  
Tetsuya Ito ◽  
André B P van Kuilenburg ◽  
Albert H Bootsma ◽  
Anja J Haasnoot ◽  
Arno van Cruchten ◽  
...  

Abstract Background: A rapid and specific screening method for patients at risk of inherited disorders of purine and pyrimidine metabolism is desirable because symptoms are varied and nonspecific. The aim of this study was to develop a rapid and specific method for screening with use of liquid urine samples or urine-soaked filter paper strips. Methods: Reverse-phase HPLC was combined with electrospray ionization (ESI), tandem mass spectrometry (MS/MS), and detection performed by multiple reaction monitoring. Transitions and instrument settings were established for 17 purines or pyrimidines. Stable-isotope-labeled reference compounds were used as internal standards when available. Results: Total analysis time of this method was 15 min, approximately one-third that of conventional HPLC with ultraviolet detection. Recoveries were 96–107% in urine with added analyte, with two exceptions (hypoxanthine, 64%; xanthine, 79%), and 89–110% in urine-soaked filter paper strips, with three exceptions (hypoxanthine, 65%; xanthine, 77%; 5-hydroxymethyluracil, 80%). The expected abnormalities were easily found in samples from patients with purine nucleoside phosphorylase deficiency, ornithine transcarbamylase deficiency, molybdenum cofactor deficiency, adenylosuccinase deficiency, or dihydropyrimidine dehydrogenase deficiency. Conclusions: HPLC-ESI MS/MS of urine allows rapid screening for disorders of purine and pyrimidine metabolism. The filter paper strips offer the advantage of easy collection, transport, and storage of the urine samples.


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