The characterisation of selected antidepressant drugs using electrospray ionisation with ion trap mass spectrometry and with quadrupole time‐of‐flight mass spectrometry and their determination by high‐performance liquid chromatography/electrospray ionisation tandem mass spectrometry

Abstract

The electrospray ionisation ion trap tandem mass spectrometry (ESI-MS(n)) of selected antidepressant drugs, i.e., citalopram, fluoxetine, mirtazapine, paroxetine, sertraline, and venlafaxine, has been investigated. Sequential product ion fragmentation experiments (MS(n)) have been performed in order to elucidate the degradation pathways for the [M+H](+) ions and their predominant product ions. These MS(n) experiments show certain characteristic fragmentations in that functional groups are generally cleaved from the ring systems as molecules such as H(2)O, amines and phenols. When an aromatic entity is present in a drug molecule together with a nitrogen-containing saturated ring structure as with mirtazapine, fragmentation initially occurs at the latter ring with the former being predictably resistant to fragmentation. Also, when an amine-containing drug molecule such as fluoxetine also contains a functional group, which liberates a phenol with a significantly lower DeltaH(f) (0) value than that of the corresponding amine, the phenol is preferentially liberated. The structures of product ions proposed for ESI-MS(n) can be supported by electrospray ionisation quadrupole-time-of-flight tandem mass spectrometry (ESI-QToF-MS/MS). These molecules can be identified and determined in mixtures at low ng/mL concentrations by the application of high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry (HPLC/ESI-MS(2)), which can also be used for their analysis in hair samples.

Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

“…This was done to establish the optimal NCE value that would allow, through MS 2 spectra, to analyze the structural stability of the sample, as this parameter has been used to predict drug metabolites at given NCE values as recommended by the MS manufacturer (25 or 30%) [32,44]. The third experiment was also done by tandem-MS at a fixed NCE value of 30%, for subsequent MS n analysis of the main fragment generated on the previous MS n−1 fragmentation (n = 3, 4).…”

“…to time-of-flight mass spectrometry (ToF-MS) [31,32,35]. ESI-MS n studies of antimalarial compounds as bisthiazolium or quinolines can be found on reports by Nicolas et al [38] or Smyth et al and O'Donnell et al [34,39], respectively.…”

The chemical fate of paroxetine metabolites. Dehydration of radicals derived from 4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine

“…12,38 The existence of VIII as an intermediate in the degradation of III has also been confirmed by using electrospray ionization mass spectrometry (ESI-MS). 11 In our quest for the possible dehydration product, the alkenes VIII and IX have been targeted as structures with chemical formula matching the experimentally observed signal (m/z 192). The most favorable pathway which precedes the formation of VIII and IX corresponds to the loss of water from carbon-centered radical cation 5.…”

“…According to other experimental studies, hydrolysis and dehydration of paroxetine can result in several products with a molecular mass of 191. 2,[11][12][13] Therefore, in addition to the photoproduct IV, additional structures V-XI (Scheme 1) which match the observed MS signal should be considered as possible degradation products of paroxetine.…”

Flow Injection Spectrophotometric Determination of Fluoxetine in Bulk and in Pharmaceutical Preparations

“…Reported methods for the determination of fluoxetine are mainly based on high performance liquid chromatography [2][3][4][5][6][7][8][9] and Gas chromatography [10][11][12] . Spectrofluoremetric methods have also used by few researchers [13][14][15] .…”