Kinetic method for enantiomeric determination of thyroid hormone (d,l-thyroxine) using electrospray ionization tandem mass spectrometry (ESI-MS/MS)

Abstract. The first analytical method is presented for the identification and absolute configuration determination of all 24 aldohexose and 2-ketohexose isomers, including the D and L enantiomers for allose, altrose, galactose, glucose, gulose, idose, mannose, talose, fructose, psicose, sorbose, and tagatose. Two unique fixed ligand kinetic method combinations were discovered to create significant enough energetic differences to achieve chiral discrimination among all 24 hexoses. Each of these 24 hexoses yields unique ratios of a specific pair of fragment ions that allows for simultaneous determination of identification and absolute configuration. This mass spectrometric-based methodology can be readily employed for accurate identification of any isolated monosaccharide from an unknown biological source. This work provides a key step towards the goal of complete de novo carbohydrate analysis.

Section: Conventional Kinetic Methodsmentioning

confidence: 99%

Section: Aldohexoses-fixed Ligand Kinetic Methodsmentioning

confidence: 99%

Complete Hexose Isomer Identification with Mass Spectrometry

Nagy

Pohl

2015

“…O riginally developed for the determination of thermochemical properties of molecules in the gas phase [1], the kinetic method was further successfully utilized to differentiate and quantify enantiomers in mixture, such as amino acids [2][3][4][5], sugars [6], chiral drugs [7][8][9][10][11], and hormones [12]. 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].…”

Section: Introductionmentioning

confidence: 99%

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

Major¹,

Fouquet²,

Charles³

2011

Isomeric distinction of di-and tri-saccharides could be efficiently achieved by using data previously obtained while performing experiments aimed at discriminating monosaccharides using trimeric ion dissociation with data analysis by the kinetic method. This study shows that effects observed for lower homologues when one of the partners is changed in the metal/reference system (typically a transition metal divalent cation associated to amino acids) can be extrapolated to upper homologues, at least for the tested analyte series. Systems allowing galactose, glucose, and fructose distinction were used as starting conditions to resolve cellobiose, lactose, maltose, and saccharose disaccharides. When a unique dissociation reaction was observed from the trimeric clusters, a new reference was selected based on its propensity to favor the analyte or the reference release, as revealed from monosaccharide experiments, depending on the desired effect. The same approach could be implemented from data obtained for disaccharides to select efficient metal/ reference systems to distinguish cellotriose, isomaltotriose, maltotriose, and panose trisaccharides. As a result, method optimization is greatly improved due to an enhanced rationalization of the search for discriminant systems. While 40 systems had to be tested for monosaccharides, by screening five transition metals and eight amino acids, the proposed approach allowed efficient metal/reference systems to be found for disaccharides after testing 18 combinations; then, only four systems had to be scrutinized to achieve trisaccharide distinction. Accurate quantitative analyses could be performed in binary mixtures using three-point calibration curves to correct for competition effects between analytes for the formation of the trimeric clusters.

“…The thermochemical properties that the method can access include proton affinity [15][16][17], gas-phase basicity [17][18][19][20], ionization energy [21], and metal ion affinity [22][23][24] to name a few. It has also been found useful in the differentiation and determination of enantiomers [25][26][27][28][29] and isomers [29 -34] under sterically-controlled conditions. The kinetic method has many interesting characteristics; it is fast, easy, and accurate, which are true even for polar and nonvolatile samples.…”

mentioning

confidence: 99%

“…In our previous work, we have reported the enantiomeric analysis of thyroid hormones, D, L-T 4 [26] and chiral drug DOPA (D, L-DOPA) [27] by kinetic method using ESI-MS/MS. In the present report, the single ratio kinetic method is utilized as a simple but rapid and sensitive method for discriminating the two isomers and furthermore the molar percentages of T 3 and rT 3 isomers in the mixture without prior separation in mainly metal-mediated ionic complexes using an ion trap and a QTOF mass spectrometer.…”

mentioning

confidence: 99%

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

Kumar

Jin

et al. 2010

Self Cite

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)