Method for analyzing deuteration rate and method for predicting deuteration rate

Abstract

The present disclosure relates to mass spectrometry using deuterated samples and methods of predicting the deuterated rate of deuterated samples.

Description

Technical Field

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority based on Korean Patent Application No. 10-2023-0078348 filed on June 19, 2023, and all contents disclosed in the Korean patent application document are incorporated into this specification.

[0003] The present disclosure relates to a method for analyzing a deuterated sample using mass spectrometry and predicting the deuteration rate of the deuterated sample. Background Art

[0004] Hydrogen is the most abundant element in the universe and is found in many compounds on Earth, including water.

[0005] 1-Hydrogen ( 1 H) and deuterium ( 2 H) is an isotope of hydrogen. 1- Hydrogen's nucleus consists of only one proton, while deuterium's nucleus consists of one proton and one neutron.

[0006] Due to this difference in the number of neutrons, the atomic weights of 1-hydrogen and deuterium show a weight difference of 1 Dalton, and similarly, even in a compound molecule in which 1-hydrogen is substituted with deuterium, the molecular weight of the compound shows a weight difference of 1 Dalton depending on the number of substitutions.

[0007] This difference in atomic weight can lead to differences in physical and chemical characteristics, such as higher boiling and melting points for deuterium than for 1-hydrogen. Compounds in which hydrogen positions are replaced by deuterium also exhibit similar properties to conventional hydrogen ( 1 H) bonded compounds have similar chemical and physical characteristics but may exhibit some different behavior due to isotope effects.

[0008] By utilizing these chemical and physical characteristics, the presence or absence of materials, reactions, and pathways can be tracked through deuterium labeling (D-labeling), in which hydrogen atoms in molecules are replaced by deuterium atoms. Therefore, deuterium is widely used as an analytical tracer for functional materials in various fields such as agriculture, medicine, and natural sciences.

[0009] In particular, in organic light-emitting diode (OLED) materials, which have become increasingly common in recent years, when 1-hydrogen is replaced by deuterium at specific positions, it exhibits superior luminous efficiency and lifetime compared to 1-hydrogen isotopes. Therefore, research is underway to replace 1-hydrogen positions in luminescent materials with deuterium.

[0010] However, as described above, since compounds containing only 1-hydrogen (hereinafter, 1-hydrogen compounds) and compounds in which hydrogen is substituted with deuterium (hereinafter, deuterated compounds) are very similar in physical and chemical characteristics other than molecular weight, when 1-hydrogen compounds and deuterated compounds, particularly compounds in which hydrogen is substituted at different positions or the number of deuterium substitutions is different, are mixed, it is difficult to find out the substitution rate, etc. by analysis.

[0011] Therefore, research is needed to develop methods for accurately confirming substitution rates and the like in samples containing deuterated compounds. Summary of the Invention

[0012] [Technical Issues]

[0013] An object of the present disclosure is to provide an analytical method that can accurately confirm the deuteration rate in a sample containing a deuterated compound.

[0014] Another object of the present disclosure is to provide a method that can predict the deuteration rate of a product during the preparation process of a deuterated compound.

[0015] [Technical solution]

[0016] The present specification provides a method for analyzing the deuteration rate of a sample material, the method comprising: step 1: obtaining a mass spectrum of a sample of the analysis object material, wherein the analysis object material contains one or more compounds selected from the group of chemical species represented by {C(0, n), C(1, n), C(2, n), C(3, n), ..., C(i, n), C(i+1, n), ..., C(n-1, n), C(n, n)}; step 2: expressing the mass spectrum of the sample material as a linear combination of the mass spectra of each element compound belonging to the group; and step 3: calculating the relative content value of each element compound belonging to the group from the coefficients of the linear combination.

[0017] In the compounds C(i,n) of each element constituting the group, C refers to compounds that are identical to the compounds of each element constituting the group except that they are substituted with hydrogen or deuterium, n refers to the total number of hydrogen and deuterium bonding sites in the compound C molecule, i refers to the number of deuterium substitutions in the element compound contained in the group, and C(i,n) refers to a compound in which i of the total n hydrogen and deuterium bonding sites are substituted with deuterium.

[0018] The group {C(0,n), C(1,n), C(2,n), C(3,n), ..., C(i,n), C(i+1,n), ..., C(n-1,n), C(n,n)} can also be expressed in another way as follows. {C(i,n)|C(i,n) is a compound where i=0-n}; in the compound C(i,n) as each element constituting the group, C means that the compounds as each element constituting the group are identical to each other except that they are substituted with hydrogen or deuterium, n represents the total number of hydrogen and deuterium bonding sites in the compound C molecule, i represents the number of deuterium substitutions in the element compound species included in the group, and C(i,n) represents a compound in which i of a total of n hydrogen and deuterium bonding sites are substituted with deuterium.

[0019] In some cases, the sample material to be analyzed may contain only pure materials in which the number or substitution position of deuterium is the same as each other, or may be in a mixture state that is a mixed state of a group of compounds in which the number or substitution position of deuterium is different from each other.

[0020] According to one embodiment, step 1 may be a step of obtaining a mass spectrum by MALDI-TOF MS measurement using an inorganic oxide matrix.

[0021] According to one embodiment, the inorganic oxide matrix may be an inorganic oxide matrix including at least one element selected from silicon, zirconium, aluminum, cerium, and the like.

[0022] According to one embodiment, step 2 may use the natural abundance ratio of the isotopes to eliminate the effects caused by the isotopes.

[0023] According to one embodiment, step 2 may represent the mass spectrum of the sample material as a linear combination of the mass spectra of each elemental compound belonging to the group using a least squares approximation method.

[0024] According to one embodiment, the method of analyzing the deuteration rate of a sample material may further include step 4: calculating an average deuteration rate of the sample material from the relative content value of each element compound belonging to the group.

[0025] According to one embodiment, step 4 may calculate the average deuteration rate of the sample material according to the following mathematical formula 1:

[0026] [Mathematical formula 1]

[0027]

[0028] In Mathematical Formula 1, SD (%) is the average deuterium substitution rate of the sample material to be analyzed, n refers to the total number of hydrogen and deuterium bonding sites in the compound C molecule, and P iis the relative amount (%) of compound C(i,n) in which i of the total n hydrogen and deuterium bonding sites is substituted with deuterium.

[0029] According to one embodiment, P i It can be calculated according to the following mathematical formula 2.

[0030] [Mathematical formula 2]

[0031]

[0032] In Mathematical Formula 2, P i is the relative amount (%) of compound C(i,n) in which i of a total of n hydrogen and deuterium bonding sites is substituted with deuterium, and ai is the weight of the C(i,n) molecule.

[0033] This specification also provides a method for predicting the deuteration rate of a reaction product, comprising: a step of measuring the average deuteration rate of a first reactant by the above method, a step of measuring the average deuteration rate of a second reactant by the above method, and a step of predicting the deuteration rate of a reaction product obtained by a reaction between the first reactant and the second reactant using the average deuteration rate of the first reactant and the average deuteration rate of the second reactant.

[0034] As used in this specification, the terms “first”, “second”, etc. are used to explain various components in this specification, and these terms are only used to distinguish one component from other components.

[0035] The technical terms used in this specification are only used to explain exemplary embodiments and are not intended to limit the scope of the present disclosure.

[0036] The singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0037] It should be understood that the terms "comprises", "includes", "has" and the like are used in this specification to specify the presence of the features, integers, steps, components or combinations thereof, but do not exclude the presence or addition of one or more other features, integers, steps, components or combinations thereof.

[0038] Although the present disclosure may have various forms and various modifications thereto, specific embodiments will be illustrated and explained in detail below. However, it is not intended to limit the present disclosure to the specific disclosure, and it should be understood that the present disclosure includes all modifications, equivalents or substitutes thereof without departing from the concept and technical scope of the present disclosure.

[0039] Hereinafter, the present disclosure will be described in detail.

[0040] According to one aspect of the present disclosure, a method for analyzing the deuteration rate of a sample material is provided, comprising: step 1: obtaining a mass spectrum of a sample of an analysis object material, wherein the analysis object material contains one or more compounds selected from the group of chemical species represented by {C(0, n), C(1, n), C(2, n), C(3, n), ..., C(i, n), C(i+1, n), ..., C(n-1, n), C(n, n)}; step 2: expressing the mass spectrum of the sample material as a linear combination of the mass spectra of each element compound belonging to the group; and step 3: calculating the relative content value of each element compound belonging to the group from the coefficients of the linear combination.

[0041] In the compound C(i,n) of each element constituting the group, C represents that the compounds of each element constituting the group are identical compounds except that they are substituted by hydrogen or deuterium, n represents the total number of hydrogen and deuterium bonding sites in the compound C molecule, i represents the number of deuterium substitutions in the element compound contained in the group, and C(i,n) represents a compound in which i of a total of n hydrogen and deuterium bonding sites are substituted by deuterium.

[0042] The group {C(0, n), C(1, n), C(2, n), C(3, n), ..., C(i, n), C(i+1, n), ..., C(n-1, n), C(n, n)} can also be expressed in other ways as follows. {C(i, n)|C(i, n) is a compound where i=0-n}; in the compound C(i, n) as each element constituting the group, C means that the compounds as each element constituting the group are identical to each other except that they are substituted with hydrogen or deuterium, n means the total number of hydrogen and deuterium bonding sites in the compound C molecule, i means the number of deuterium substitutions in the element compound species included in the group, and C(i, n) means a compound in which i of a total of n hydrogen and deuterium bonding sites are substituted with deuterium.

[0043] In a compound C having the same elemental composition and interatomic bonding relationship except that they are substituted with hydrogen or deuterium, when there are n sites to which hydrogen or deuterium is bonded, a compound having a structure in which no deuterium is substituted at all, that is, a 1-hydrogen compound having a deuterium substitution number of 0, can be represented by C(0,n). Furthermore, a compound having a structure in which one of the n substitution sites is substituted with deuterium instead of hydrogen, that is, a deuterated compound having a deuterium substitution number of 1, can be represented by C(1,n), a compound in which i of the n substitution sites is substituted with deuterium instead of hydrogen, that is, a deuterated compound having a deuterium substitution number of i, can be represented by C(i,n), and a deuterated compound having a structure in which all n of the n substitution sites are substituted with deuterium instead of hydrogen, that is, a deuterated compound having a deuterium substitution number of n, can be represented by C(n,n).

[0044] Here, the sample material to be analyzed may contain one or more chemical species selected from the group of chemical species represented by {C(0,n), C(1,n), C(2,n), C(3,n),..., C(i,n), C(i+1,n),..., C(n-1,n), C(n,n)}.

[0045] That is, the sample material to be analyzed may contain only pure materials in which the number or position of deuterium substitution is exactly the same, or may be in a mixed state of a group of compounds in which the number or position of deuterium substitution is different from each other.

[0046] The present specification provides a method for finding the average deuteration rate of a sample material to be analyzed (which is a pure material or a mixture) by mass spectrometry analysis, that is, the ratio of the number of deuterium atoms present in the sample material to the total number of hydrogen or deuterium atoms.

[0047] First, a mass spectrum of a sample of an analysis target material is obtained, wherein the analysis target material contains one or more compounds selected from the group of chemical species represented by {C(0,n), C(1,n), C(2,n), C(3,n), ..., C(i,n), C(i+1,n), ..., C(n-1,n), C(n,n)}.

[0048] According to one embodiment, mass spectra can be obtained by MALDI-TOF MS measurements using a spectroscopic inorganic oxide matrix.

[0049] The inorganic oxide matrix may be an inorganic oxide matrix containing at least one element selected from silicon, zirconium, aluminum, and cerium. More specifically, the inorganic oxide may be silica, zirconium oxide, aluminum oxide, ceria, or other inorganic oxides in which silicon, zirconium, aluminum, and / or cerium atoms are mixed into their crystal lattices, but the present disclosure is not limited thereto.

[0050] When the number of deuterium substitutions increases by 1, the mass number of the molecule also increases by 1. Since the above-mentioned inorganic oxide matrix does not generate a signal due to the material itself in MALDI-TOF MS analysis and can produce a single ion species for the sample material to be analyzed, it is possible to eliminate the influence of the mass number increase by 1 due to further bonding of another hydrogen to the molecule during MS analysis, and it is possible to only reveal the influence of the mass number increase by 1 due to deuterium substitution or the influence of the mass number increase due to isotopes of elements other than deuterium (such as carbon, etc.) constituting the compound.

[0051] Figure 1 and Figure 2 is an example of a typical mass spectrum obtained by MALDI-TOF MS analysis.

[0052] assumed Figure 1This is a spectrum obtained by analyzing a sample containing the above-mentioned compound C(i,n) by MALDI-TOF MS.

[0053] exist Figure 1 The highest peak at the center is the isotope of an element that does not contain deuterium (e.g. 13 C. 14 C, etc.), and the molecular weight at this time is defined as M0. However, in fact, Figure 1 The mother peak MO is not a peak appearing from a single chemical species, but rather a combination of peaks from several chemical species with the same mass number and the same charge.

[0054] For example, the mother peak corresponding to M0 appears from the sum of the contributing parts described below.

[0055] i) A radical ion C(i,n) formed by losing an electron from a compound C(i,n) +· Contributed part;

[0056] ii) a radical ion C(i-1,n) formed by losing one electron from a compound C(i-1,n) (mass number: M0-1) having one less deuterium substitution number than that of the compound C(i,n) +· (mass number: M0-1), isotopes of elements contained therein (e.g., 13 C) the fraction contributed by the compound present (mass number: M0);

[0057] iii) Compound C(i-1, n)+H + (mass number: M0) contributed by another hydrogen atom, wherein another hydrogen atom is further bonded to a radical ion C(i-1,n) formed by losing one electron from a compound C(i-1,n) (mass number: M0-1) having one less deuterium substitution number than the compound C(i,n) +· ;

[0058] iv) a portion contributed by a compound (mass number: M0) in which a compound C(i-2,n) (mass number: M0-2) having two less deuterium substitutions than the compound C(i,n) loses one electron to form a radical ion C(i-2,n) +· , another hydrogen atom is further bonded to the radical ion C(i-2,n) +· (mass number: M0-1), and one of the elements contained therein exists as an isotope with a mass number +1 (for example, one of the carbon atoms is 13 C);

[0059] v) a radical ion C(i-2,n) formed by losing one electron from a compound C(i-2,n) (mass number: M0-2) having two less deuterium substitutions than the compound C(i,n) +· (mass number: M0-2), one of the elements contained therein is an isotope with a mass number of +2 (for example, a carbon atom is 14 C) the fraction contributed by the compound present (mass number: M0);

[0060] vi) a radical ion C(i-2,n) formed by losing one electron from a compound C(i-2,n) (mass number: M0-2) having two less deuterium substitutions than the compound C(i,n) +· (mass number: M0-2), one of the elements contained therein is represented by two isotopes having a mass number of +1 (for example, two carbon atoms are 13 C) The fraction of the compound present (mass number: M0) that contributes to...

[0061] By the same logic as above, another hydrogen is further bonded during the MS measurement process, or due to the isotopes of the elements present in the molecule (e.g. 13 C. 14 C) The mass number can increase or decrease, and chemical species with the same charge-to-mass ratio are detected as one peak. This also applies to peaks other than the parent peak.

[0062] However, according to one embodiment, when MALDI-TOF MS measurement is performed using an inorganic oxide matrix, the increase in mass number by 1 due to further bonding of hydrogen can be eliminated, and only the effects due to deuterium substitution and isotopes of elements other than deuterium (e.g., carbon, etc.) can be exhibited.

[0063] assumed Figure 2 This is a spectrum obtained by performing MALDI-TOF MS analysis on a sample containing the above-mentioned compound C(i,n) using an inorganic oxide matrix.

[0064] in this case, Figure 2 The parent peak in appears as the sum of the contributing parts mentioned below.

[0065] i) A radical ion C(i,n) formed by losing an electron from a compound C(i,n) +· Contributed part;

[0066] ii) a radical ion C(i-1,n) formed by losing one electron from a compound C(i-1,n) (mass number: M0-1) having one less deuterium substitution number than that of the compound C(i,n) +·(mass number: M0-2), one of the elements contained therein is an isotope with a mass number +1 (for example, one of the carbon atoms is 13 C) the fraction contributed by the compound present (mass number: M0);

[0067] iii) a radical ion C(i-2,n) formed by losing one electron from a compound C(i-2,n) (mass number: M0-2) having two less deuterium substitutions than the compound C(i,n) +· (mass number: M0-2), two of the elements contained therein are isotopes with a mass number of +1 (for example, two carbon atoms are 13 C) the fraction contributed by the compound present (mass number: M0);

[0068] iv) a radical ion C(i-2,n) formed by losing one electron from a compound C(i-2,n) (mass number: M0-2) having two less deuterium substitutions than the compound C(i,n) +· (mass number: M0-2), one of the elements contained therein is an isotope with a mass number of +2 (for example, one of the carbon atoms is 14 C) The fraction contributed by the compound present (mass number: M0) ... By the same logic as above, due to the number of deuterium substitutions or the isotopes of elements present in the molecule (e.g., isotopes of carbon atoms, such as 13 C. 14 C) The mass number can increase or decrease by one, and chemical species with the same charge-to-mass ratio are detected as one peak. This also applies to peaks other than the parent peak.

[0069] Therefore, if the effects due to isotopes (eg, carbon isotopes) can be eliminated, only the effects due to the number of deuterium substitutions can remain.

[0070] According to one embodiment, in step 2, the mass increase effect due to isotopes other than deuterium can be eliminated by using isotopes, particularly the natural abundance ratio of elements (e.g., carbon, etc.) constituting the compound. That is, in the sample material to be analyzed in the present disclosure, part or all of the 1-hydrogen in a specific compound is intentionally replaced by deuterium, and the deuterium abundance ratio in the sample material to be analyzed can be different from the natural abundance ratio of deuterium.

[0071] However, in the sample material to be analyzed in the present disclosure, unless there are special cases, other constituent elements other than deuterium, specifically, for example, isotopes of elements such as carbon, oxygen, and nitrogen, exist according to the natural abundance ratios of the corresponding isotopes.

[0072] For example, it is known that carbon ( 12C) has a natural abundance of about 98.9%; carbon with mass number 13 ( 13 C) has a natural abundance of about 1.1%; carbon with mass number 14 ( 14 The natural abundance ratio of carbon isotopes is approximately 0.0000000001%. Therefore, by utilizing this natural abundance ratio, the effects of carbon isotopes can be eliminated from the obtained mass spectrum.

[0073] In another example, since it is known that oxygen with mass number 16 ( 16 O) has a natural abundance of about 99.757%; oxygen with mass number 17 ( 17 The natural abundance ratio of O) is about 3.8×10 -4 ; oxygen with mass number 18 ( 18 The natural abundance ratio of O) is about 2.05×10 -3 By utilizing this natural abundance ratio, the effects due to oxygen isotopes can be removed from the resulting mass spectrum.

[0074] In another embodiment, nitrogen having a mass number of 14 ( 14 N) has a natural abundance of about 99.636%; nitrogen with a mass number of 15 ( 15 The natural abundance ratio of nitrogen isotopes is about 0.364%. Therefore, by utilizing this natural abundance ratio, the effects due to nitrogen isotopes can be eliminated from the obtained mass spectrum.

[0075] In addition to the above elements, if the compound contains an element having isotopes, the influence due to the isotopes, that is, the influence due to the mass number change, can be eliminated by utilizing the natural abundance ratio of the isotopes.

[0076] According to one embodiment, in step 2, the mass spectrum of the sample material can be expressed as a linear combination of the mass spectra of each elemental chemical species belonging to the group using a least squares approximation method.

[0077] That is, each peak appearing in a mass spectrum obtained by analyzing the entire sample material to be analyzed is separated into a linear combination of the mass spectrum of each elemental chemical species contained in the material to be analyzed, which can be considered as a kind of deconvolution.

[0078] Figure 3 is a schematic diagram illustrating the concept of deconvolution according to one embodiment of the present disclosure.

[0079] exist Figure 3 , 100 is each peak appearing in a mass spectrum obtained by analyzing the entire sample material to be analyzed, and 200 is a peak that can appear in a theoretical mass spectrum according to the number of deuterium substitutions of a material having a specific chemical formula.

[0080] For ease of explanation, 200 is first described, which is a peak that may appear in a theoretical mass spectrum depending on the number of deuterium substitutions of a material having a specific chemical formula.

[0081] The molecular weight of C(i,n) is assumed to be M0.

[0082] if Figure 3 210 in is a theoretical peak represented by C(i,n) (mass number: M0), then C(i,n) has a fixed number of deuterium substitutions i, therefore, each peak at 210 retains only the effect due to the isotope (e.g., carbon isotope), which can be explained as follows.

[0083] M0: i.0) is composed of C(i, n) +· Peaks generated by free radical ions.

[0084] M0+1: i.1) ​​by C(i, n) +· An isotope with mass number +1 (e.g. 13 C) Resulting peaks.

[0085] M0+2: i.2.1) by C(i, n) +· An isotope with mass number +2 (e.g. 14 C) generated peak; i.2.2) by C (i, n) +· Two isotopes with mass number +1 (e.g., two 13 C) Resulting peaks.

[0086] M0+3: i.3.1) by C(i, n) +· An isotope with mass number +2 (e.g. 14 C) and an isotope with mass number +1 (e.g. 13 C) generated peak; i.3.2) by C (i, n) +· Three isotopes with mass number +1 (e.g., three 13 C) Resulting peaks.

[0087] M0+4: i.4.1) by C(i, n) +· Two isotopes with mass number +2 (e.g., two 14 C) generated peak, i.4.2) by C(i,n) +· An isotope with mass number +2 (e.g. 14 C) and two isotopes with mass number +1 (e.g., two 13 C) generated peak, i.4.2) by C(i,n) +· Four isotopes with mass number +1 (e.g., four 13 C) Resulting peaks.

[0088] if Figure 3 220 in is a theoretical peak appearing from C(i+1,n) (mass number: M0+1), and C(i+1,n) has the number of deuterium substitutions fixed to i+1, so each peak of 220 retains only the effect due to carbon isotope generation, which can be explained as follows.

[0089] M0: Not present.

[0090] M0+1:i+1.0) is composed of C(i+1,n) +· Peaks generated by free radical ions.

[0091] M0+2:i+1.1) is composed of C(i+1,n) +· An isotope with mass number +1 (e.g. 13 C) Resulting peaks.

[0092] M0+3: i+1.2.1) by C(i+1, n) +· An isotope with mass number +2 (e.g. 14 C) generated by the peak; i+1.2.2) by C(i+1, n) +· Two isotopes with mass number +1 (e.g., two 13 C) Resulting peaks.

[0093] M0+4:i+1.3.1) by C(i+1,n) +· An isotope with mass number +2 (e.g. 14 C) and an isotope with mass number +1 (e.g. 13 C) generated by the peak; i+1.3.2) by C(i+1, n) +· Three isotopes with mass number +1 (e.g., three 13 C) Resulting peaks.

[0094] if Figure 3 230 in is a theoretical peak appearing due to C(i+2,n) (mass number: M0+2). C(i+2,n) has the number of deuterium substitutions fixed at i+2, so each peak of 230 retains only the effect due to carbon isotope generation, which can be explained as follows.

[0095] M0: Not present.

[0096] M0+1: Did not appear.

[0097] M0+2:i+2.0) is composed of C(i+2,n) +· Peaks generated by free radical ions.

[0098] M0+3: i+2.1) is obtained from C(i+2,n) +· An isotope with mass number +1 (e.g. 13 C) Resulting peaks.

[0099] M0+4: i+2.2.1) by C(i+2,n) +· An isotope with mass number +2 (e.g. 14 C) generated peak; i+2.2.2) by C(i+2,n) +· Two isotopes with mass number +1 (e.g., two 13 C) Resulting peaks.

[0100] Considering the above, Figure 3 The 100 in is again explained as follows.

[0101] Assuming that the mass number that eliminates the isotope effect (e.g., carbon isotope) in C(i,n) is M0, then Figure 3 Each peak in the 100s appears by the sum of the following elements.

[0102] M0: i.0)C(i, n) +· Contribution of free radical ions.

[0103] M0+1:i.1)C(i,n) +· An isotope with mass number +1 (e.g. 13 C) contribution, and i+1.0)C(i+1,n) +· Contribution of free radical ions.

[0104] M0+2: i.2.1)C(i, n) +· An isotope with mass number +2 (e.g. 14 C) contribution, i.2.2) C(i, n) +· Two isotopes with mass number +1 (e.g., two 13 Contribution of C), i+1.1)C(i+1, n) +· An isotope with mass number +1 (e.g. 13 C) contribution, and i+2.0)C(i+2,n) +· Contribution of free radical ions.

[0105] M0+3: i.3.1) C(i, n) +· An isotope with mass number +2 (e.g. 14 C) and an isotope with mass number +1 (e.g. 13 C) contribution, i.3.2) C(i, n) +·Three isotopes with mass number +1 (e.g., three 13 Contribution of C), i+1.2.1) C(i+1, n) +· An isotope with mass number +2 (e.g. 14 Contribution of C), i+1.2.2) C(i+1, n) +· Two isotopes with mass number +1 (e.g., two 13 C) contribution, and i+2.1) C(i+2,n) +· An isotope with mass number +1 (e.g. 13 C) contribution.

[0106] M0+4: i.4.1)C(i, n) +· Two isotopes with mass number +2 (e.g. 14 C) contribution, i.4.2) C(i, n) +· An isotope with mass number +2 (e.g. 14 C) and two isotopes with mass number +1 (e.g., two 13 C) contribution, i.4.2) C(i, n) + Four isotopes with mass number +1 (e.g., four 13 Contribution of C), i+1.3.1) C(i+1, n) +· An isotope with mass number +2 (e.g. 14 C) and an isotope with mass number +1 (e.g. 13 Contribution of C), i+1.3.2) C(i+1, n) +· Three isotopes with mass number +1 (e.g., three 13 Contribution of C), i+2.2.1) C(i+2,n) +· An isotope with mass number +2 (e.g. 14 C) contribution, and i+2.2.2) C(i+2,n) +· Two isotopes with mass number +1 (e.g., two 13 C) contribution.

[0107] However, as mentioned above, it is known that carbon ( 12 C) has a natural abundance of about 98.9%; carbon with mass number 13 ( 13 C) has a natural abundance of about 1.1%; carbon with mass number 14 ( 14 C) is about 0.0000000001%. Therefore, in terms of probability, even if 14 C's contribution or two or more13 The contribution of C is ignored and the final analysis result may not be significantly different in arithmetic calculations, thus simplifying the calculations.

[0108] Furthermore, according to the same principle, based on the chemical species C(i,n) having a mass number M0, there may be no significant difference even if peaks of M0+5 or higher are ignored.

[0109] That is, since each peak appearing in the mass spectrum obtained by analyzing the entire sample material to be analyzed appears by a linear combination of each peak in the mass spectrum appearing by each chemical species contained in the sample material to be analyzed, this can be reversed, and each peak appearing in the mass spectrum obtained by analyzing the entire sample material can be separated again into a linear combination of mass spectrum peaks appearing by each chemical species contained in the sample material to be analyzed.

[0110] An example of this method is the least squares approximation method, etc. In the case of the least squares approximation method, the coefficient values ​​used in the linear combination of each peak in the mass spectrum appearing from each chemical species, that is, Figure 3 A in 200 i 、a i+1 、a i+2 …can be thought of as ratios of each chemical species.

[0111] According to one embodiment of the present disclosure, the mass spectrum can be analyzed by the above method to find the ratios a0, a1, a2, a3, ..., a4 of each group of elements of each chemical species contained in the sample of the material to be analyzed, that is, {C(0, n), C(1, n), C(2, n), C(3, n), ..., C(i, n), C(i+1, n), ..., C(n-1, n), C(n, n)}. i 、……、a n-1 、a n When the group is rearranged by including the ratio of each chemical species, it can be expressed as follows. {C(0,n)×a0, C(1,n)×a1, C(2,n)×a2, C(3,n)×a3, ..., C(i,n)×a i , C(i+1,n)×a i+1 ,...,C(n-1,n)×a n-1 , C(n,n)×a n}]

[0112] According to one embodiment, the method of analyzing the deuteration rate of a sample material may further comprise step 4: calculating an average deuteration rate of the sample material based on the relative content value of each element chemical species belonging to the group.

[0113] According to one embodiment, step 4 may calculate the average deuteration rate of the sample material according to the following mathematical formula 1:

[0114] [Mathematical formula 1]

[0115]

[0116] In Mathematical Formula 1,

[0117] SD (%) is the average deuterium substitution rate of the sample material to be analyzed, n refers to the total number of hydrogen and deuterium bonding sites in the compound C molecule, P i is the relative amount (%) of compound C(i,n) in which i of a total of n hydrogen and deuterium bonding sites is substituted with deuterium.

[0118] According to one embodiment, P i It can be calculated according to the following mathematical formula 2.

[0119] [Mathematical formula 2]

[0120]

[0121] In Mathematical Formula 2, P i is the relative amount (%) of compound C(i,n) in which i of the total n hydrogen and deuterium bonding sites is replaced by deuterium, a i is the weight of the C(i,n) molecule.

[0122] That is, the above mathematical formula merely summarizes the set {C(0,n)×a0, C(1,n)×a1, C(2,n)×a2, C(3,n)×a3, ..., C(i,n)×a i , C(i+1,n)×a i+1 ,…,C(n-1,n)×a n-1 , C(n,n)×a n}, and the present disclosure is not necessarily limited thereto.

[0123] At the same time, the present specification provides a method for predicting the deuteration rate of a reaction product, comprising: a step of measuring the average deuteration rate of a first reactant by the above method, a step of measuring the average deuteration rate of a second reactant by the above method, and a step of predicting the deuteration rate of a reaction product obtained by the reaction between the first reactant and the second reactant using the average deuteration rate of the first reactant and the average deuteration rate of the second reactant.

[0124] In other words, according to the above method, in a chemical reaction in which a specific reactant substituted with deuterium reacts to form a reaction product, even when a separate analysis of the reaction product is not performed, the relative amount of the number of deuterium substitutions and the average substitution rate obtained by deuterium substitution rate analysis can be used to predict the relative amount of the number of substitutions of each chemical species present in the reaction product and the average deuterium substitution rate of all chemical species.

[0125] Hereinafter, a reaction in which two molecules react to form one molecule will be described as an example.

[0126] The reaction of two molecules substituted with deuterium at specific positions to form one molecule can be divided into the following three cases.

[0127] i) In the first case, when a deuterium-substituted compound (hereinafter referred to as compound 1-1) and a deuterium-unsubstituted compound (hereinafter referred to as compound 1-2) react to form a product (hereinafter referred to as compound 1), the functional group at a specific position of compound 1-1 is replaced by compound 1-2;

[0128] ii) In the second case, when a deuterium-substituted compound (hereinafter referred to as compound 2-1) and a deuterium-unsubstituted compound (hereinafter referred to as compound 2-2) react to form a product (hereinafter referred to as compound 2), the deuterium substitution position of compound 2-1 remains intact;

[0129] iii) In the third case, a deuterium-substituted compound (hereinafter referred to as compound 3-1) reacts with another deuterium-substituted compound (hereinafter referred to as compound 3-2) to form a product (hereinafter referred to as compound 3).

[0130] The first case will be described first.

[0131] Figure 4 is a conceptual diagram for explaining changes in deuterium substitution characteristics in a reaction according to one embodiment.

[0132] exist Figure 4 In the above, compound 1-1 is a deuterium compound substituted by deuterium, compound 1-2 is a molecule not substituted by deuterium, and compound 1-2 is substituted at a specific substitution position X of compound 1-1 to form compound 1.

[0133] In this case, the probability that the X position of compound 1-1 is 1-hydrogen is a. The value of a can be arithmetically determined using the "average substitution rate" value of the deuterium-substituted reaction product obtained by the above-mentioned mass analysis, or a substitution rate value obtained by other methods such as NMR analysis can be used.

[0134] In this case, the relative amount P() per deuterium substitution number in the compound 1 as a product can be expressed by the following Mathematical Formula 3-1.

[0135] [Mathematical formula 3-1]

[0136] P i (Compound 1) = {P i+1 (Compound 1-1)×(1-a)}+{P i (Compound 1-1) × a}

[0137] In the above formula, P() is the relative amount of molecules substituted with deuterium at position i, and a is the probability of the presence of the original hydrogen at the substitution position x of compound 1-1.

[0138] In this case, the average deuteration rate (SD1) of the product can be expressed by the following mathematical formula 3-2.

[0139] [Mathematical formula 3-2]

[0140]

[0141] Next, the second case will be described.

[0142] Figure 5 is a conceptual diagram for explaining changes in deuterium substitution characteristics in a reaction according to one embodiment.

[0143] exist Figure 5 In the embodiment, compound 2-1 is a compound substituted with deuterium, and compound 2-2 is a compound not substituted with deuterium. The portion of the substitution position of compound 2-1 to which the substituent X was originally attached is substituted by compound 2-2 to form compound 2.

[0144] In this case, the relative amount P() of deuterium substitution in the product compound 2 is the same as the relative amount P() of each deuterium substitution number in the reactant compound 2-1, and thus can be represented by the following mathematical formula 4-1.

[0145] [Mathematical formula 4-1]

[0146] P i (Compound 2)=P i (Compound 2-1)

[0147] In this case, the average deuteration rate (SD2) of the product can be expressed by the following mathematical formula 4-2.

[0148] [Mathematical formula 4-2]

[0149]

[0150] Next, the third case will be described.

[0151] Figure 6 is a conceptual diagram for explaining changes in deuterium substitution characteristics in a reaction according to one embodiment.

[0152] exist Figure 6 In the embodiment, compound 3-1 and compound 3-2 are deuterium compounds substituted by deuterium, and in the substitution position of compound 3-1, the part to which the original substituent X is connected is replaced by compound 3-2 to form compound 3.

[0153] In this case, in the compound 3 as a product, the relative amount P() according to the number of deuterium substitution can be expressed by the following Mathematical Formula 5-1.

[0154] [Mathematical formula 5-1]

[0155] P i (Compound 3) = σ (m = 0 to i) {P m (Compound 3-1)×P i-m (Compound 3-2)}

[0156] In this case, the average deuteration rate (SD3) of the product can be expressed by the following mathematical formula 5-2.

[0157] [Mathematical formula 5-2]

[0158]

[0159] When a deuterated compound is reacted to produce another deuterated compound using the above method, even if a separate deuterium substitution analysis is not performed on the product, the relative amount P () of each deuterium substitution number in the product and the average deuteration rate of the product can be predicted by the deuterium substitution analysis results of the reactants.

[0160] [Beneficial Effects]

[0161] According to one embodiment of the present disclosure, the relative amount of each deuterium substitution number and the average deuterium substitution rate in the sample to be analyzed can be accurately found through MS analysis, and even when a separate deuterium substitution analysis is not performed on the product, the relative amount P() of each deuterium substitution number and the average deuterium substitution rate of the product can be predicted by the deuterium substitution analysis results of the reactants. BRIEF DESCRIPTION OF THE DRAWINGS

[0162] Figure 1 and Figure 2 is an example of a typical mass spectrum obtained by MALDI-TOF MS analysis.

[0163] Figure 3 is a schematic diagram illustrating the concept of deconvolution according to one embodiment of the present disclosure.

[0164] Figures 4 to 6 is a conceptual diagram for explaining changes in deuterium substitution characteristics in a reaction according to one embodiment.

[0165] Figure 7 is a MALDI-TOF mass spectrum of a compound according to one embodiment.

[0166] Figure 8 is a MALDI-TOF mass spectrum of a compound according to one embodiment.

[0167] Figure 9 is the result of NMR analysis of a compound according to one embodiment.

[0168] Figure 10 is a MALDI-TOF mass spectrum of a compound according to one embodiment. DETAILED DESCRIPTION

[0169] Hereinafter, the effects and functions of the present invention will be described in more detail by way of specific examples. However, these examples are given for illustrative purposes only, and the scope of the present invention is not limited thereto.

[0170] <Example>

[0171] In the reaction of the compounds shown below, the deuteration rates of the precursors and intermediates (reactants) are analyzed, and the deuteration rates of the products produced by the reaction between the first intermediate and the second intermediate are predicted.

[0172] First Precursor:

[0173]

[0174] First intermediate:

[0175]

[0176] Second precursor:

[0177] Second intermediate:

[0178]

[0179] Reaction diagram:

[0180] First precursor -> first intermediate; second precursor -> second intermediate; first intermediate + second intermediate -> product:

[0181]

[0182] First, preliminary experiments were performed to select an appropriate matrix for analysis.

[0183] Preparation of analytical samples (preparation example)

[0184] 1 mg of Al2O3 powder was added to 300 μL of tetrahydrofuran (THF) to prepare the Al2O3 matrix solution.

[0185] Separately, 1 mg of a material to be analyzed (the second intermediate in the H-form) was dissolved in 1 mL of THF to prepare a solution of the material to be analyzed.

[0186] The Al2O3 matrix solution was shaken, and 10 μL of the solution was taken while Al2O3 was dispersed, and mixed with 10 μL of the material solution to be analyzed to prepare a mixed solution.

[0187] 1 μL of the mixed solution was taken and placed on a MALDI sample plate and allowed to dry naturally to prepare a sample.

[0188] Preparation of analytical samples (refer to preparation example)

[0189] 1 mg of dihydroxybenzoic acid was added to 100 μL of tetrahydrofuran (THF) to prepare an organic matrix solution.

[0190] Separately, 1 mg of a material to be analyzed (the second intermediate in the H-form) was dissolved in 1 mL of THF to prepare a solution of the material to be analyzed.

[0191] 10 μL of the organic matrix solution was taken and mixed with 10 μL of the analyte solution to prepare a mixed solution.

[0192] 1 μL of the mixed solution was taken and placed on a MALDI sample plate and allowed to dry naturally to prepare a sample.

[0193] Mass spectra acquisition and analysis

[0194] MALDI-TOF MS experimental conditions:

[0195] Sampling rate: 2.5 GS / s or higher; Laser repetition rate: 100 or 200 Hz; Laser conditions: emission at raster point (50), limiting diameter (500 μm); Mass spectrometer: positive mode

[0196] Figure 7 is the MALDI-TOF mass spectrum of the second intermediate (H-form).

[0197] Reference Figure 7 It can be confirmed that in the case of the reference preparation example using an organic matrix, the peak intensity of 331 is increased compared to the preparation example using an inorganic oxide matrix.

[0198] This is believed to be due to the effect of the mass number increase that occurs when further hydrogen atoms are bonded during analysis. Depending on the type of matrix, chemical species in which hydrogen atoms further bond to the molecule may be generated, making it difficult to eliminate the effects of this mass number change. In other words, when analyzing deuterium-substituted compounds, in addition to the mass number increase of 1 due to deuterium substitution and the effects of mass number increases due to isotopes of elements other than deuterium that constitute the compound, the mass number increase due to hydrogenation is also reflected, potentially reducing analytical accuracy.

[0199] Therefore, in the following experiments of this example, experiments were conducted using a series of inorganic oxide matrices.

[0200] Preparation of analytical samples

[0201] 1 mg of Al2O3 powder was added to 300 μL of tetrahydrofuran (THF) to prepare the Al2O3 matrix solution.

[0202] Separately, 1 mg of a material to be analyzed was dissolved in 1 mL of THF to prepare a solution of the material to be analyzed.

[0203] The Al2O3 matrix solution was shaken, and 10 μL of the solution was taken while Al2O3 was dispersed, and mixed with 10 μL of the material solution to be analyzed to prepare a mixed solution.

[0204] 1 μL of the mixed solution was taken and placed on a MALDI sample plate and allowed to dry naturally to prepare a sample.

[0205] Mass spectrometry acquisition and analysis

[0206] MALDI-TOF MS experimental conditions:

[0207] Sampling rate: 2.5 GS / s or higher; Laser repetition rate: 100 or 200 Hz; Laser conditions: emission at raster point (50), limiting diameter (500 μm); Mass spectrometer: positive mode

[0208] Analysis of the average deuteration rate of the first precursor

[0209] (Mass spectrometry results)

[0210] Figure 8 is the MALDI-TOF mass spectrometry of the first precursor.

[0211] In the first precursor compound, the number of deuterium substitution sites is 16 in total and the number of carbons is 24, so each compound contained in the first precursor compound can be represented by C(i,16), where i=0 to 16.

[0212] In this analysis result, since the above-mentioned hydrogen (1 H), so if the effect of isotopes can be eliminated here, only the effect of the number of deuterium substitutions can be left. Since the first precursor compound contains only carbon in addition to hydrogen or deuterium, if the effect of carbon isotopes can be eliminated in the analysis results, the effect of the number of deuterium substitutions can be confirmed.

[0213] Using about 98.9% carbon ( 12 C) natural abundance ratio; about 1.1% of carbon ( 13 C) of natural abundance; and about 0.0000000001% by mass of carbon ( 14 C)'s natural abundance ratio, Figure 8 The effects of carbon isotopes were eliminated from the mass spectrum, and this was again separated into the linear combination of each peak of the mass spectrum appearing for each chemical species, and each coefficient value was calculated, rounded to the first decimal place, and summarized in Table 1 below.

[0214] {C(0,16)×a0, C(1,16)×a1, C(2,16)×a2, C(3,16)×a3,…, C(i,16)×a i , C(i+1,16)×a i+ 1,...,C(15,16)×a15,C(16,16)×a16}

[0215] [Table 1]

[0216] Number of deuterium substitutions (i) 12 13 14 15 16 <![CDATA[Relative ratio (P i )]]> 2 11 29 40 18

[0217] The average deuteration rate was calculated using Mathematical Formula 1 and was found to be approximately 91.2%.

[0218] [Mathematical formula 1]

[0219]

[0220] Among them, n=16.

[0221] Figure 9 The results of NMR analysis of the first precursor are shown.

[0222] Figure 9 The results of NMR analysis showed that the probability a that the ring position A-1 of the first precursor was 1-hydrogen was about 6.8%.

[0223] Prediction of the average deuteration rate of the first intermediate

[0224]

[0225] In the reaction, the reactive site of the first precursor is a site that can be substituted with deuterium, and this site is replaced by Br in the first intermediate. Since this corresponds to the first case above, the average substitution rate of the first intermediate can be calculated using Mathematical Formulas 3-1 and 3-2.

[0226] In the following mathematical formula 3-1, the probability a that the ring position A-1 of the first precursor is 1-hydrogen can use the "average substitution rate" value of the deuterium substitution reaction product obtained by mass analysis, or the substitution rate value obtained by NMR analysis or the like.

[0227] [Mathematical formula 3-1]

[0228] P i (First Intermediate) = {P i+1 (first precursor)×(1-a)}+{P i (first precursor) × a}

[0229] Furthermore, the average deuteration rate (SD1) of the first intermediate can be obtained by the following mathematical formula 3-2.

[0230] [Mathematical formula 3-2]

[0231]

[0232] Among them, n=15.

[0233] In Table 2 below, the values ​​actually measured experimentally for the first intermediate and the values ​​predicted by the above method are summarized.

[0234] [Table 2]

[0235]

[0236] *In calculating the predicted value, the average substitution rate value obtained by mass spectrometry was used as the value a in Mathematical Formula 3-1.

[0237] **When calculating the predicted value, the deuteration rate value at the functional group substitution site (X) obtained by NMR analysis was used as the value a in Mathematical Formula 3-1.

[0238] From Table 2, it can be confirmed that the tendency of the ratio according to each substitution number is the same between the value measured by the actual experiment and the predicted value, and the value of the average substitution ratio is obtained with almost no error.

[0239] Analysis of the average deuteration rate of the second precursor

[0240] Figure 10 is the MALDI-TOF mass spectrum of the second precursor.

[0241] In the second precursor compound, the number of deuterium substitution sites is 11 in total and the number of carbons is 16, so each compound contained in the first precursor compound can be represented by C(i,11), where i=0 to 11.

[0242] In this analysis result, since the above-mentioned hydrogen ( 1 H), so if the effect of isotopes can be eliminated here, only the effect of the number of deuterium substitutions will remain. Since the second precursor compound contains carbon and chlorine in addition to hydrogen or deuterium, if the effect of carbon and chlorine isotopes can be eliminated in the analysis results, the effect of the number of deuterium substitutions can be confirmed.

[0243] Use about 98.9% 12 The natural abundance of C is about 1.1% 13 The natural abundance of C is about 0.0000000001% 14 The natural abundance ratio of C is about 75.8% 35 The natural abundance ratio of Cl; and about 24.2% 37 The natural abundance ratio of Cl, from Figure 10 The effects of carbon isotopes and chlorine isotopes were eliminated from the mass spectrum, each peak of the mass spectrum was separated into a linear combination of each chemical species, and each coefficient value was calculated, rounded to the first decimal place, and summarized in Table 3.

[0244] {C(0,11)×a0, C(1,11)×a1, C(2,11)×a2, C(3,11)×a3,…, C(i,11)×a i , C(i+1,11)×a i+1 ,...,C(10,11)×a 10 , C(11,11)×a 11}

[0245] [Table 3]

[0246] Number of deuterium substitutions (i) 6 7 8 9 10 11 <![CDATA[Relative ratio (P i )]]> 1 7 22 36 30 4

[0247] Furthermore, the average deuteration rate was calculated using Mathematical Formula 1 and was found to be approximately 81.7%.

[0248] [Mathematical formula 1]

[0249]

[0250] Among them, n=11.

[0251] Prediction of the average deuteration rate of the second intermediate

[0252]

[0253] In the reaction, the reactive site of the second precursor is the site where Cl is located, and since this site is replaced by the tetramethyl-1,3,2-dioxaborolane compound in the second intermediate, this corresponds to the second case described above.

[0254] Therefore, if the deuterium substitution pattern and ratio of the second intermediate are predicted using the results of Table 3 above, they can be shown in Table 4 below.

[0255] In Table 4 below, the values ​​based on actual experimental results and the predicted values ​​are summarized together.

[0256] [Table 4]

[0257]

[0258] From Table 4, it can be confirmed that the trends of the ratios of the respective substitution numbers are the same between the actual experimental values ​​and the predicted values, and that the average substitution rate values ​​have almost no error.

[0259] Prediction of the average deuteration rate of products

[0260]

[0261] In the reaction, a product is formed by a reaction between a first intermediate and a second intermediate.

[0262] The reactive site of the first intermediate is B r The reaction site of the second intermediate is the site substituted by the tetramethyl-1,3,2-dioxaborolane compound, therefore, this corresponds to the third case mentioned above.

[0263] Therefore, if the deuterium substitution patterns and ratios of the products are predicted using the results of Table 2 and Table 2a, they can be shown in Table 5 below.

[0264] In Table 5 below, the values ​​based on actual experimental results and the predicted values ​​are summarized together.

[0265] [Table 5]

[0266]

[0267]

[0268] From Table 5, it can be confirmed that the trends of the ratios according to the respective numbers of substitutions are the same between the actual experimental values ​​and the predicted values, and that the average substitution ratio values ​​have almost no error.

Claims

1. A method for analyzing the deuteration rate of a sample material, comprising: Step 1: Obtaining a mass spectrum of a sample of an analysis target material, wherein the analysis target material contains one or more compounds selected from the group of chemical species represented by {C(0,n), C(1,n), C(2,n), C(3,n), ..., C(i,n), C(i+1,n), ..., C(n-1,n), C(n,n)}; Step 2: expressing the mass spectrum of the sample material as a linear combination of the mass spectra of each elemental compound belonging to the group; and Step 3: Calculate the relative content value of each element compound belonging to the group from the coefficient of the linear combination: In the compound C(i,n) of each element constituting the group, C refers to compounds that are the same as compounds of each element constituting the group except that they are substituted with hydrogen or deuterium, n refers to the total number of hydrogen and deuterium bonding sites in the compound C molecule, i refers to the number of deuterium substitutions in the element compounds contained in the group, C(i,n) refers to a compound in which i of a total of n hydrogen and deuterium bonding sites is replaced with deuterium.

2. The method for analyzing the deuteration rate of a sample material according to claim 1, wherein: The step 1 is a step of obtaining a mass spectrum by MALDI-TOF MS measurement using an inorganic oxide matrix.

3. The method for analyzing the deuteration rate of a sample material according to claim 1, wherein: The inorganic oxide matrix is ​​an inorganic oxide matrix including at least one element selected from silicon, zirconium, aluminum, and cerium.

4. The method for analyzing the deuteration rate of a sample material according to claim 1, wherein: Step 2 further includes the step of eliminating the effects caused by the isotopes using the natural abundance ratio of the isotopes.

5. The method for analyzing the deuteration rate of a sample material according to claim 1, wherein: The step 2 expresses the mass spectrum of the sample material as a linear combination of the mass spectra of each element compound belonging to the group using the least squares approximation method. 6 . The method for analyzing the deuteration rate of a sample material according to claim 1 , further comprising step 4 : calculating an average deuteration rate of the sample material based on the relative content value of each element compound belonging to the group.

7. The method for analyzing the deuteration rate of a sample material according to claim 6, wherein: Step 4 calculates the average deuterium substitution rate of the sample material according to the following mathematical formula 1: [Mathematical formula 1] In Mathematical Formula 1, SD (%) is the average deuteration rate of the sample material to be analyzed, n refers to the total number of hydrogen and deuterium bonding sites in the compound C molecule, P i is the relative amount (%) of compound C(i,n) in which i of a total of n hydrogen and deuterium bonding sites is substituted with deuterium.

8. The method for analyzing the deuteration rate of a sample material according to claim 7, wherein: P i Calculate according to the following mathematical formula 2: [Mathematical formula 2] In Mathematical Formula 2, P i is the relative amount (%) of compound C(i,n) in which i of a total of n hydrogen and deuterium bonding sites is replaced by deuterium, ai is the weight of the C(i,n) molecule.

9. A method for predicting the deuteration rate of a reaction product, comprising: the step of measuring the average deuteration rate of the first reactant by the method according to claim 1, a step of measuring the average deuteration rate of the second reactant by the method according to claim 1, and The step of predicting a deuteration rate of a reaction product obtained by a reaction between the first reactant and the second reactant using the average deuteration rate of the first reactant and the average deuteration rate of the second reactant.

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