Isotope effect in negative ion chemical ionization mass spectrometry of deuterium labelled lormetazepam

Abstract

This study identified the reason for the poor quantification of lormetazepam-TMS (1) using negative ion chemical ionization with lormetazepam-1,1,1-2H3-TMS (2) as an internal standard. Mass spectra of lormetazepam and its deuterium labelled compounds determined at various ion source temperatures (100-250 degrees C) gave almost the same behaviour for 1 and lormetazepam-3',4',5',6'-2H4-TMS (3) but a different one for 2, suggesting that the poor quantification was due to an isotope effect. This was confirmed by the findings that the ratios of ion currents of the base peaks of 1 and 3 were independent of the ion source temperature but those of 1 and 2 varied markedly with it. This phenomenon was also observed in the mass fragmentography of the molecular ion, although to a lesser degree than that of the above fragment. In both positive ion chemical ionization and electron impact ionization modes, no isotope effect arose because there was no corresponding fragment to cause the isotope effect.

Quantitative trace analysis by combined chromatography and mass spectrometry using external and internal standards

“…A dramatic example of this effect has been published. 28 It is good practice to establish whether or not such an effect is operating by comparing mass spectra of the analyte and its isotopelabelled analogue, as a function of ion-source temperature, ionizing energy etc.…”

Production and Application of Stable Isotope-Labeled Internal Standards for RNA Modification Analysis

“…These heavy isotopologues of the target analyte have the same physico-chemical properties as the analyte and thus they can be used to correct for mass spectrometric detection fluctuations. The use of deuterium (D) is also possible, but here some physico-chemical properties vary (e.g., retention time) and thus D-labeled isotopomers are not ideal as internal standards [12]. The production of a heavy labeled compound can be done either synthetically [13] or by metabolic labeling [14].…”