Isomeric discrimination and quantification of thyroid hormones, T₃ and rT₃, by the single ratio kinetic method using electrospray ionization mass spectrometry

Abstract

The single ratio kinetic method is applied to the discrimination and quantification of the thyroid hormone isomers, 3,5,3=-triiodothyronine and 3,3=,5=-triiodothyronine, in the gas phase, based on the kinetics of the competitive unimolecular dissociations of singly charged transition-metal ion-bound trimeric complexes [M II (A)(ref*) 2 -H] ϩ (M II ϭ divalent transitionmetal ion; A ϭ T 3 or rT 3 ; ref* ϭ reference ligand). The trimeric complex ions are generated using electrospray ionization mass spectrometry and the ions undergo collisional activation to realize isomeric discrimination from the branching ratio of the two fragment pathways that form the dimeric complexesThe ratio of the individual branching ratios for the two isomers R iso is found strongly dependent on the references and the metal ions. Various sets are tried by choosing the reference from amino acids, substituted amino acids, and dipeptides in combination with the central metal ion chosen from five transition-metal ions (Co II , Cu II , Mn II , Ni II , and Zn II ) for the complexes in this experiment. The results are compared in terms of the isomeric discrimination for the T 3 /rT 3 pair. Calibration curves are constructed by relating the ratio of the branching ratios against the isomeric composition of their mixture to allow rapid quantitative isomer analysis of the sample pair. Furthermore, the instrument-dependence of this method is investigated by comparing the two sets of results, one obtained from a quadrupole ion trap mass spectrometer and the other from a quadrupole time-of-flight mass spectrometer. (J Am Soc Mass Spectrom 2010, 21, 14 -22)

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

“…Many analytical techniques have been applied for the enantiomeric differentiation, which include circular dichroism, cyclic voltametry, fluorescence spectroscopy, nuclear magnetic resonance, conventional chromatography, capillary electrophoresis and mass spectrometry . Among all, mass spectrometry stands as a powerful technique because of its salient features like sensitivity, speed and tolerance to impurity . Though, a number of mass spectral techniques are being used for the enantiomeric differentiation, the electrospray ionization tandem mass spectrometry (ESI‐MS/MS) with Cooks' kinetic method emerged as a potential technique and applied to various class of compounds (Scheme ) …”

Direct differentiation of stereoisomers of ezetimibe/ambrisentan/atorvastatin and their mechanism study by electrospray ionization quadrupole time‐of‐flight mass spectrometry

“…In the CR method, chiral differentiation can be attained by measuring the abundance ratio of the product ion to the precursor ion. These two methods have been successfully utilized to recognize and quantify different classes of pharmaceutical compounds, including β‐blockers, antiviral nucleoside, sugars, potassium channel opener, and other compounds …”

“…These two methods have been successfully utilized to recognize and quantify different classes of pharmaceutical compounds, including β-blockers, [15][16][17][18] antiviral nucleoside, 19 sugars, 20 potassium channel opener, 18,21 and other compounds. [22][23][24][25] Also, some drug formulations are composed of two or more different pure optical enantiomers, which improves clinical efficiency.…”

Isomeric Distinction of Small Oligosaccharides: A Bottom-Up Approach Using the Kinetic Method

“…For the same classes of compounds, the kinetic method has also proven relevant for the distinction of isomers, as reported for peptides [13][14][15][16] and amino acids [17], monosaccharides [18] and thyroid hormones [19]. The fundamental concept of isomeric distinction is based on the fact that the nature of the A i isomer involved in the trimeric cluster [ 2 -H] + by loss of the analyte as a neutral on another hand.…”

“…Indeed, best references for isomeric discrimination of monosaccharides using the kinetic method were found to be those amino acids possessing a hydroxyl group, compared with an additional acidic function or an additional amine group [18]. Similarly, using systems involving dipeptides and a transition metal were found to allow T 3 and rT 3 thyroid hormones to be differentiated [19].…”