CN114034757A - Reagent and method for analyzing chiral structure of flurbiprofen molecule - Google Patents

Reagent and method for analyzing chiral structure of flurbiprofen molecule Download PDF

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CN114034757A
CN114034757A CN202011047491.7A CN202011047491A CN114034757A CN 114034757 A CN114034757 A CN 114034757A CN 202011047491 A CN202011047491 A CN 202011047491A CN 114034757 A CN114034757 A CN 114034757A
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flurbiprofen
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cyclodextrin
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calcium
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CN114034757B (en
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方向
戴新华
江游
彭涛
徐福兴
吴芳玲
古连城
余绍宁
丁传凡
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National Institute of Metrology
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Abstract

The invention relates to a chiral analysis reagent and a method for a common medicament-Flurbiprofen (Flurbiprofen) molecule. The method comprises the following steps: firstly, a flurbiprofen chiral molecule sample, cyclodextrin and a compound containing metal ions are prepared into a solution, then an ion generating device, such as a compound ion prepared by an electrospray ionization ion source, is utilized, and finally an ion mobility spectrometer device capable of measuring ion collision cross sections is utilized to measure the ion mobility spectrum of the compound ion containing different chiral flurbiprofen molecules, so that the chiral structure of the flurbiprofen molecules contained in the sample can be obtained. The analytical reagent and the method provided by the invention have the advantages of simplicity, accuracy, high analysis speed and the like, and are simpler than the existing chiral analytical method of flurbiprofen molecules.

Description

Reagent and method for analyzing chiral structure of flurbiprofen molecule
Technical Field
The invention relates to the technical field of analysis and detection, in particular to a reagent for analyzing a flurbiprofen molecular chiral structure and a method thereof.
Background
The medicine is one of basic weapons for human to overcome diseases, nearly half of more than 2000 kinds of commonly used medicine molecules are chiral medicines, and research and practice show that different chiral medicine molecules often have different clinical effects, for example, for a chiral medicine composed of the same kind of molecules, one enantiomer of the chiral medicine is effective, and the other enantiomer is ineffective or has small effect; sometimes one enantiomer is therapeutically effective, while the other enantiomer is toxic to the body; also, different enantiomer molecules exhibit disparate therapeutic effects, and the like, and therefore, it is of great value to analyze and understand the presence or absence or amount of various chiral enantiomers in chiral drugs, both in drug development and in drug manufacturing processes.
Flurbiprofen (flurbiprofen) is a chiral drug with two enantiomers, is a common drug clinically used for treating rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and the like at present, and has a chemical name of (+/-) -2- (2-fluoro-4-biphenyl) -propionic acid. Chinese alias: flurbiprofen; ibuprofen fluoride; 2- (2-fluoro-4-biphenyl) propionic acid; flurbiprofen; ibuprofen diflufenican; english name: flurbiprofen; english alias: flurbiprofen; (iii) a Cebutid; ANSID; ANSIDE; 2- (2-fluorobethyl-4-yl) propionic Acid;
some of its basic chemical properties are that flurbiprofen is very soluble in methanol, ethanol, acetone or ether, soluble in acetonitrile and practically insoluble in water. Its melting point is 110-.
The molecular formula of flurbiprofen is C15H13FO2Molecular weight is 244.27, and its molecular structure is shown in FIG. 1.
Flurbiprofen is one of the most commonly used drugs at present, is mainly clinically suitable for rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and the like, and can also be used for symptomatic treatment of soft tissue diseases (such as sprains and strains) and mild and moderate pains (such as dysmenorrheal, postoperative pain, toothache and the like). The anti-inflammatory effect and the analgesic effect of the compound are respectively 250 times and 50 times of that of aspirin, the compound is stronger than ibuprofen, and the compound is lower in toxicity and is the strongest one of the currently known propionic acid non-steroidal anti-inflammatory drugs.
At present, the common analysis method for chiral drug molecules is to first separate molecules containing two or more chiral structures, i.e. chiral drug resolution. Common separation methods are: chiral high performance liquid chromatography, chiral capillary electrophoresis, chiral gas chromatography, chiral thin layer chromatography, circular dichroism, nuclear magnetic resonance, supercritical fluid chromatography, etc. Then the structure analysis is carried out on the resolved molecular system only containing a single chiral structure to obtain the chiral property, namely the chiral property belongs to levorotation or dextrorotation. Another method for analyzing the structure of chiral molecules is so-called derivatization, which utilizes different reactivity or reaction processes of chiral molecules with different structures and other molecules, such as chiral reagents, to generate different product molecules, and then analyzes different reaction products to obtain the structure and content information of the original chiral molecules. In summary, the existing methods for analyzing chiral molecular structures must separate or derivatize chiral molecules before analysis.
The mass spectrometry is the most commonly used molecular or atomic mass analysis technology, which can rapidly analyze the mass-to-charge ratio or mass information of different atoms or molecules, but has no effect on chiral molecules with the same mass-to-charge ratio and molecular mass. The ion mobility spectrometry technology can analyze molecules with different structures like a fractal, and the working principle and the process of the ion mobility spectrometry technology are that ions of a sample to be analyzed are firstly generated and then are introduced into the ion mobility spectrometry, and the general ion mobility spectrometry works under the low vacuum condition. In the ion mobility spectrometry, sample ions make directional motion under the action of an electric field and continuously collide with nonreactive working gases in the mobility spectrometry, such as nitrogen, argon and the like. Different ions are separated by their different mobilities due to their different collision cross-sections. Information on the structure of the ion or molecule can be obtained from the separated ion mobility spectrum obtained. However, because the resolution capability of the current ion mobility spectrometry is low, the difference of molecular structures is small, or molecules are very small, such as small organic molecules, small molecular drugs, etc., the ion mobility spectrometry technology still cannot analyze the structural difference, especially the different chiral structural difference, such as the chiral structural analysis of flurbiprofen molecules.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a reagent for analyzing a chiral structure of flurbiprofen molecules and a method thereof.
The technical scheme for realizing the purpose of the invention is as follows: a reagent for analyzing a chiral structure of a flurbiprofen molecule comprises the flurbiprofen molecule mixed with a solvent, cyclodextrin and a compound containing monovalent or divalent metal ions, wherein the cyclodextrin is one of gamma cyclodextrin and beta cyclodextrin, and the compound containing the monovalent or divalent metal ions is one of a compound containing monovalent lithium ions and a compound containing divalent calcium ions.
In the reagent of the technical scheme, the concentration of the flurbiprofen molecule serving as the solvent is 10-12About 1 mol/l, the concentration of the gamma cyclodextrin is 10-12About 1 mol/l, the concentration of beta-cyclodextrin is 10-12About 1 mol/l, the concentration of the compound containing divalent calcium ions is 10-121 mol/l, the concentration of the compound containing monovalent lithium ions is 10-12About 1 mol/l.
The flurbiprofen molecule in the technical scheme has two chiral structures of an R-type and an S-type.
The compound containing divalent calcium ions in the technical scheme is one of salt containing calcium ions, alkali containing calcium ions and complex containing calcium ions; the compound containing monovalent lithium ions is one of a salt containing lithium ions, a base containing lithium ions and a complex containing lithium ions.
The gamma cyclodextrin in the technical scheme also comprises a derivative of the gamma cyclodextrin; the beta-cyclodextrin also includes derivatives of beta-cyclodextrin.
The solvent in the technical scheme is one or more of water, methanol, ethanol and acetic acid.
A method for analyzing the chiral structure of flurbiprofen molecules, comprising the following steps:
s1, adding a solvent into flurbiprofen molecules, gamma cyclodextrin and a compound containing divalent calcium ions to be subjected to chiral structure analysis to prepare a flurbiprofen-gamma cyclodextrin-calcium ion mixture;
s2, the mixture of flurbiprofen-gamma cyclodextrin-calcium ion is used as an ion source to generate univalent positive ion of flurbiprofen-gamma cyclodextrin-calcium ion, namely, (C)15H13FO2-γCD-Ca2+-H+)+Mass to charge ratio ofM/e＝1524Th；
S3, measuring the ion collision cross section of the monovalent positive ions of the flurbiprofen-gamma cyclodextrin-calcium ions, or measuring the ion mobility spectrum of the monovalent positive ions of the flurbiprofen-gamma cyclodextrin-calcium ions by using an ion mobility spectrum experimental device, so as to obtain the chiral structure information of the flurbiprofen molecules;
in S2, the flurbiprofen-gamma cyclodextrin-calcium ion mixture is in a liquid state or in a solid state prepared from the liquid state according to experimental analysis.
Another method for analyzing the chiral structure of flurbiprofen molecules comprises the following steps:
s1, adding a solvent into flurbiprofen molecules to be subjected to chiral structure analysis, gamma cyclodextrin and a compound containing monovalent lithium ions to prepare a flurbiprofen-gamma cyclodextrin-lithium ion mixture;
s2, the flurbiprofen-gamma cyclodextrin-lithium ion mixture is used as an ion source to generate the divalent positive ion of the flurbiprofen-gamma cyclodextrin-lithium ion, namely, (C)15H13FO2-γCD-3Li+-H+)2+The mass-to-charge ratio is M/e which is 781 Th;
s3, measuring the ion collision cross section of the bivalent positive ions of the flurbiprofen-gamma cyclodextrin-lithium ions, or measuring the ion mobility spectrum of the bivalent positive ions of the flurbiprofen-gamma cyclodextrin-lithium ions by using an ion mobility spectrum experimental device, so as to obtain the chiral structure information of the flurbiprofen molecules;
in S2, the flurbiprofen-gamma cyclodextrin-lithium ion mixture is in a liquid state or in a solid state prepared from the liquid state according to experimental analysis.
Another method for analyzing the chiral structure of flurbiprofen molecules comprises the following steps:
s1, adding a solvent into the flurbiprofen molecule to be subjected to chiral structure analysis, the beta-cyclodextrin and the compound containing divalent calcium ions to prepare a flurbiprofen-beta-cyclodextrin-calcium ion mixture;
s2, producing the mixture of flurbiprofen-beta cyclodextrin-calcium ion by using ion sourceFlurbiprofen-beta cyclodextrin-a monovalent cation of calcium ion, i.e. (C)15H13FO2-βCD-Ca2+-H+)+The mass-to-charge ratio is M/e-1419 Th;
s3, measuring the ion collision cross section of the monovalent positive ions of the flurbiprofen-beta cyclodextrin-calcium ions, or measuring the ion mobility spectrum of the monovalent positive ions of the flurbiprofen-beta cyclodextrin-calcium ions by using an ion mobility spectrum experimental device, so as to obtain the chiral structure information of the flurbiprofen molecules;
in S2, the flurbiprofen-beta cyclodextrin-calcium ion mixture is in a liquid state or in a solid state prepared from the liquid state according to experimental analysis.
In the above technical solution S1, the ion source is one of an electrospray ionization ion source, a laser-assisted desorption ionization ion source, and a desorption electrospray ionization ion source; in S3, the experimental device is one of an ion mobility spectrometry and a composite experimental device including an ion mobility spectrometry.
After the technical scheme is adopted, the invention has the following positive effects:
the invention provides a chiral analysis reagent and a method for a common medicament-Flurbiprofen (Flurbiprofen) molecule. The method comprises the following steps: firstly, a flurbiprofen chiral molecule sample, cyclodextrin and a compound containing metal ions are prepared into a solution, then an ion generating device, such as a compound ion prepared by an electrospray ionization ion source, is utilized, and finally an ion mobility spectrometer device capable of measuring ion collision cross sections is utilized to measure the ion mobility spectrum of the compound ion containing different chiral flurbiprofen molecules, so that the chiral structure of the flurbiprofen molecules contained in the sample can be obtained. Furthermore, if the sample contains levorotatory flurbiprofen and dextrorotatory flurbiprofen molecules, the method provided by the invention can also obtain the information of the relative content of the levorotatory flurbiprofen and the dextrorotatory flurbiprofen.
Obviously, the method for analyzing the chiral structure of the flurbiprofen molecule provided by the invention is simple, the flurbiprofen chiral molecule does not need to be subjected to pre-chiral resolution or derivatization, and the used chemical sample is easy to obtain, low in price, non-toxic and harmless. Compared with the method commonly used at present, the method has many advantages.
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In order that the present disclosure may be more readily and clearly understood, reference is now made to the following detailed description of the present disclosure taken in conjunction with the accompanying drawings, in which
Fig. 1 is a schematic diagram of two chiral molecular structures of flurbiprofen molecules.
FIG. 2 is a schematic diagram of the molecular structure of cyclodextrin.
FIG. 3 is a graph showing the results of ion mobility spectrometry of complex ions formed by flurbiprofen molecules, gamma-cyclodextrin molecules and calcium ions, wherein the upper half portion is the ion mobility spectrometry of the complex ions formed by the mixture of R-type and S-type flurbiprofen, gamma-cyclodextrin molecules and calcium ions, and the lower half portion is the ion mobility spectrometry of the complex ions formed by the S-type flurbiprofen molecules and calcium ions;
FIG. 4 shows the results of ion mobility spectrometry of complex ions formed by flurbiprofen chiral molecules, cyclodextrin and lithium ions, the upper half is a mixture of R and S type flurbiprofen chiral molecules and three lithium ions (3 Li)+) The lower half part of the ion mobility spectrum of the generated complex ions is S-shaped flurbiprofen, beta-CD and three lithium ions (3 Li)+) Ion mobility spectrometry of the generated complex ions;
fig. 5 shows the ion mobility spectrometry result of the complex ion generated by flurbiprofen chiral molecule, beta cyclodextrin and calcium ion: the upper half part is an ion mobility spectrum of a complex ion generated by the chiral molecular mixture of the R-type flurbiprofen and the S-type flurbiprofen and the beta CD and Ca ions, and the lower half part is an ion mobility spectrum of a complex ion generated by the S-type flurbiprofen and the beta CD and Ca ions.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. The components of embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations.
The experimental device used in the invention is a commercial ion mobility spectrometry-mass spectrometry instrument, the chiral structure of flurbiprofen molecules is analyzed by a TIMS-TOFMS instrument manufactured by Bruke corporation, and the experimental results are shown in fig. 3, 4 and 5. It is clear from the experimental results that flurbiprofen molecules having different chiral structures can be easily distinguished.
In the present invention, the calcium ion-containing compound used may be a calcium ion-containing salt such as: CaCl2、Ca(NO3)2、CaSO4Calcium halide (except F), calcium nitrate, calcium chlorate, calcium perchlorate, calcium bicarbonate, calcium dihydrogen phosphate, calcium gluconate, calcium hydrogen phosphate, calcium lactate, etc., or alkali containing calcium ion, such as Ca (OH)2Alternatively, an ion-containing complex or the like may give Ca in an aqueous solution2+The compound of (1).
In the present invention, the lithium ion-containing compound used may be a lithium ion-containing salt such as: LiCl and LiNO3、Li2SO4Lithium halide (excluding F) and the like, and may be a base containing lithium ions, such as LiOH, or a compound which can give Li in an aqueous solution, such as a complex containing Li ions.
In the present invention, the ion source may be an Electrospray Ionization (ESI) ion source, a Matrix Assisted Laser Desorption Ionization (MALDI) ion source, a Desorption Electrospray Ionization (DESI) ion source, or other types of ion sources, which is not limited herein.
In the invention, the ion source can be one ion source or any arrangement combination of a plurality of different ion sources, so that a plurality of ion sources can simultaneously analyze a plurality of similar samples or different samples, and high-throughput and high-sensitivity detection can be realized.
Example 1
Firstly, respectively weighing appropriate amount of calcium chloride (CaCl)2) gamma-Cyclodextrin (gamma CD) samples using methanol/water (CH)3OH:H2O is 1:1) or acetonitrile/water mixed solution (CH)3CN:H2O is 1:1) the solutions were prepared separately as calcium chloride (CaCl) at a concentration of 10 millimoles per liter (10mmol/L)2) Mother liquor of beta-cyclodextrin; weighing a proper amount of flurbiprofen molecules, and carrying out mass transfer on the flurbiprofen molecules by using methanol: acetonitrile mixed solution (CH)3OH:CH3CN is 1:1) preparing mother liquor of flurbiprofen with concentration of 10 millimole/liter (10mmol/L), and respectively taking calcium chloride (CaCl)2) 100 μ L of mother liquor of γ -cyclodextrin and flurbiprofen was added to the sample tube, and finally, methanol: aqueous (1:1) solution and dilution to 10-4To 10-6mol/L. And then, respectively testing the chiral structures of flurbiprofen molecules by using a TIMS-TOFMS instrument manufactured by Bruke, wherein the specific experimental process comprises the steps of generating sample ions by using an electrospray ionization (ESI) ion source of the TIMS-TOFMS instrument, and carrying out mass spectrum analysis on various ion products generated by ESI. And then further analyzed using this instrument (C)15H13FO2-γCD-Ca2+-H+)+Ion mobility spectrum (as shown in fig. 3) of ion (m/e 1524Th), due to (R-C)15H13FO2-γCD-Ca2+-H+)+And (S-C)15H13FO2-γCD-Ca2+-H+)+The ions have different collision cross-sections and therefore different ion mobilities (as shown in figure 3), and by comparative analysis we obtained the analyzed C15H13FO2The chiral structure of the molecule, i.e., whether it is R-type or S-type. Meanwhile, the signal intensity of the obtained mass spectrum and the signal intensity of the obtained ion mobility spectrum are related to the concentration of a sample in the solution, so that the chiral C corresponds to a certain chirality15H13FO2The content of the chiral flurbiprofen molecules in the solution can be calculated by the ion mobility spectrum intensity of the molecules, and then the quantitative analysis can be realized.
In the experimental process, a solution with a proper concentration, namely calcium chloride (CaCl) in the solution can be prepared according to the requirement2) The concentrations of the gamma-cyclodextrin (gamma CD) and flurbiprofen molecules can be determined according to the experimental requirements. In addition, each compound is in a mixed solutionThe concentrations may be the same or different.
In the experimental process, the solvent type and relative content of the solution can be prepared according to the needs, namely the mixture of acetonitrile and methanol, the mixture of water, acetonitrile and methanol, or the mixture of any two or more of water, methanol, ethanol, acetonitrile, propionitrile, formic acid, acetone and other common reagents, and the proportion of each reagent in the mixed solution is not limited and is determined according to the needs of the experiment.
Example 2
Firstly, respectively weighing appropriate amounts of lithium chloride (LiCl), gamma-cyclodextrin (gamma CD) samples and flurbiprofen molecules (C)15H13FO2) Sample, using methanol/water (CH)3OH:H2O ═ 1:1) or acetonitrile/water mixed solution (CH)3CN:H2O is 1:1) the solution is prepared into mother liquor of lithium chloride (LiCl) and beta-cyclodextrin with the concentration of 10 millimole/liter (10mmol/L) respectively; weighing a proper amount of flurbiprofen molecules, and carrying out mass transfer on the flurbiprofen molecules by using methanol: acetonitrile mixed solution (CH)3OH:CH3CN ═ 1:1) was prepared as a mother liquor of flurbiprofen at a concentration of 10mmol/L (10mmol/L), then 100 μ L of each of the mother liquors of lithium chloride (LiCl), γ -cyclodextrin and flurbiprofen was taken into a sample tube, and finally, methanol: aqueous (1:1) solution and dilution to 10-4To 10-6mol/L. And then, respectively testing the chiral structures of flurbiprofen molecules by using a TIMS-TOFMS instrument manufactured by Bruke, wherein the specific experimental process comprises the steps of generating sample ions by using an electrospray ionization (ESI) ion source of the TIMS-TOFMS instrument, and carrying out mass spectrum analysis on various ion products generated by ESI. And then further analyzed using this instrument (C)15H13FO2-γCD-3Li+-H+)2+Ion mobility spectrum of ion (m/e 781Th) (as shown in fig. 3) due to (R-C)15H13FO2-γCD-3Li+-H+)2+And (S-C)15H13FO2-γCD-3Li+-H+)2+Ions with different collision cross-sections and therefore different ion mobilities (as shown in figure 3) were obtained by comparative analysisIs analyzed C15H13FO2The chiral structure of the molecule, i.e., whether it is R-type or S-type. Meanwhile, the signal intensity of the obtained mass spectrum and the signal intensity of the obtained ion mobility spectrum are related to the concentration of a sample in the solution, so that the chiral C corresponds to a certain chirality15H13FO2The content of the chiral flurbiprofen molecules in the solution can be calculated by the ion mobility spectrum intensity of the molecules, and then the quantitative analysis can be realized.
In the experimental process, a solution with a suitable concentration can be prepared according to the needs, that is, the concentrations of lithium chloride (LiCl), gamma-cyclodextrin (γ CD) and flurbiprofen molecules in the solution can be determined according to the needs of the experiment. Further, the concentration of each compound in the mixed solution may be the same or different.
In the experimental process, the solvent type and relative content of the solution can be prepared according to the needs, namely the mixture of acetonitrile and methanol, the mixture of water, acetonitrile and methanol, or the mixture of any two or more of water, methanol, ethanol, acetonitrile, propionitrile, formic acid, acetone and other common reagents, and the proportion of each reagent in the mixed solution is not limited and is determined according to the needs of the experiment.
Example 3
Firstly, respectively weighing appropriate amount of calcium chloride (CaCl)2) beta-Cyclodextrin (beta CD) sample, using methanol/water (CH)3OH:H2O ═ 1:1) or acetonitrile/water mixed solution (CH)3CN:H2O1: 1) solutions were prepared separately as calcium chloride (CaCl) at a concentration of 10mmol/L (10mmol/L)2) Beta-cyclodextrin mother liquor, weighing a proper amount of flurbiprofen molecules, and using methanol: acetonitrile mixed solution (CH)3OH:CH3CN 1:1) to prepare a mother solution of flurbiprofen with a concentration of 10 millimoles per liter (10mmol/L), and then respectively taking calcium chloride (CaCl)2) 100 μ L of a stock solution of β -cyclodextrin and flurbiprofen was added to the sample tube, and finally, methanol: aqueous (1:1) solution and dilution to 10-4To 10-6mol/L. Then, the chiral structure of flurbiprofen molecules is respectively tested by using a TIMS-TOFMS instrument produced by Bruke, and the instrument hasThe experimental procedure was to generate sample ions using an electrospray ionization (ESI) ion source of the TIMS-TOFMS instrument and to mass-analyze various ion products generated by ESI. And then further analyzed using this instrument (C)15H13FO2-βCD-Ca2+-H+)+Ion mobility spectrometry (as shown in fig. 3) of an ion (m/e ═ 1419th), due to (R-C)15H13FO2-βCD-Ca2+-H+)+And (S-C)15H13FO2-βCD-Ca2+-H+)+The ions have different collision cross-sections and therefore different ion mobilities (as shown in figure 3), and by comparative analysis we obtained the analyzed C15H13FO2The chiral structure of the molecule, i.e., whether it is R-type or S-type. Meanwhile, the signal intensity of the obtained mass spectrum and the signal intensity of the obtained ion mobility spectrum are related to the concentration of a sample in the solution, so that the chiral C corresponds to a certain chirality15H13FO2The content of the chiral flurbiprofen molecules in the solution can be calculated by the ion mobility spectrum intensity of the molecules, and then the quantitative analysis can be realized.
In the experimental process, a solution with a proper concentration, namely calcium chloride (CaCl) in the solution can be prepared according to the requirement2) The concentrations of the β -cyclodextrin (β CD) and flurbiprofen molecules can be determined according to experimental needs. Further, the concentration of each compound in the mixed solution may be the same or different.
In the experimental process, the solvent type and relative content of the solution can be prepared according to the needs, namely the mixture of acetonitrile and methanol, the mixture of water, acetonitrile and methanol, or the mixture of any two or more of water, methanol, ethanol, acetonitrile, propionitrile, formic acid, acetone and other common reagents, and the proportion of each reagent in the mixed solution is not limited and is determined according to the needs of the experiment.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention, and are not intended to limit the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A reagent for analyzing a chiral structure of flurbiprofen molecules, which is characterized in that: the reagent comprises a flurbiprofen molecule mixed with a solvent, cyclodextrin and a compound containing monovalent or divalent metal ions, wherein the cyclodextrin is one of gamma cyclodextrin and beta cyclodextrin, and the compound containing the monovalent or divalent metal ions is one of a compound containing monovalent lithium ions and a compound containing divalent calcium ions.
2. The reagent for the molecular chiral structure analysis of flurbiprofen according to claim 1, wherein: in the reagent, the concentration of the flurbiprofen molecule serving as the solvent is 10-12About 1 mol/l, the concentration of the gamma cyclodextrin is 10-12About 1 mol/l, the concentration of beta-cyclodextrin is 10-12About 1 mol/l, the concentration of the compound containing divalent calcium ions is 10-121 mol/l, the concentration of the compound containing monovalent lithium ions is 10-12About 1 mol/l.
3. The reagent for the molecular chiral structure analysis of flurbiprofen according to claim 1, wherein: the flurbiprofen molecule has two chiral structures of R-type and S-type.
4. The reagent for the molecular chiral structure analysis of flurbiprofen according to claim 1, wherein: the compound containing divalent calcium ions is one of a salt containing calcium ions, an alkali containing calcium ions and a complex containing calcium ions; the compound containing monovalent lithium ions is one of a salt containing lithium ions, a base containing lithium ions and a complex containing lithium ions.
5. The reagent for the molecular chiral structure analysis of flurbiprofen according to claim 1, wherein: the gamma cyclodextrin also includes derivatives of gamma cyclodextrin; the beta-cyclodextrin also includes derivatives of beta-cyclodextrin.
6. The reagent for the molecular chiral structure analysis of flurbiprofen according to claim 1, wherein: the solvent is one or more of water, methanol, ethanol and acetic acid.
7. A method for analyzing a chiral structure of a flurbiprofen molecule, comprising the steps of:
s1, adding a solvent into flurbiprofen molecules, gamma cyclodextrin and a compound containing divalent calcium ions to be subjected to chiral structure analysis to prepare a flurbiprofen-gamma cyclodextrin-calcium ion mixture;
s2, the mixture of flurbiprofen-gamma cyclodextrin-calcium ion is used as an ion source to generate univalent positive ion of flurbiprofen-gamma cyclodextrin-calcium ion, namely, (C)15H13FO2-γCD-Ca2+-H+)+The mass-to-charge ratio is M/e 1524 Th;
s3, measuring the ion collision cross section of the monovalent positive ions of the flurbiprofen-gamma cyclodextrin-calcium ions, or measuring the ion mobility spectrum of the monovalent positive ions of the flurbiprofen-gamma cyclodextrin-calcium ions by using an ion mobility spectrum experimental device, so as to obtain the chiral structure information of the flurbiprofen molecules;
in S2, the flurbiprofen-gamma cyclodextrin-calcium ion mixture is in a liquid state or in a solid state prepared from the liquid state according to experimental analysis.
8. A method for analyzing a chiral structure of a flurbiprofen molecule, comprising the steps of:
s1, adding a solvent into flurbiprofen molecules to be subjected to chiral structure analysis, gamma cyclodextrin and a compound containing monovalent lithium ions to prepare a flurbiprofen-gamma cyclodextrin-lithium ion mixture;
s2, the flurbiprofen-gamma cyclodextrin-lithium ion mixture is used as an ion source to generate the divalent positive ion of the flurbiprofen-gamma cyclodextrin-lithium ion, namely, (C)15H13FO2-γCD-3Li+-H+)2+The mass-to-charge ratio is M/e which is 781 Th;
s3, measuring the ion collision cross section of the bivalent positive ions of the flurbiprofen-gamma cyclodextrin-lithium ions, or measuring the ion mobility spectrum of the bivalent positive ions of the flurbiprofen-gamma cyclodextrin-lithium ions by using an ion mobility spectrum experimental device, so as to obtain the chiral structure information of the flurbiprofen molecules;
in S2, the flurbiprofen-gamma cyclodextrin-lithium ion mixture is in a liquid state or in a solid state prepared from the liquid state according to experimental analysis.
9. A method for analyzing a chiral structure of a flurbiprofen molecule, comprising the steps of:
s1, adding a solvent into the flurbiprofen molecule to be subjected to chiral structure analysis, the beta-cyclodextrin and the compound containing divalent calcium ions to prepare a flurbiprofen-beta-cyclodextrin-calcium ion mixture;
s2, using the ion source to generate the monovalent positive ion of flurbiprofen-beta cyclodextrin-calcium ion, namely, (C)15H13FO2-βCD-Ca2+-H+)+The mass-to-charge ratio is M/e-1419 Th;
s3, measuring the ion collision cross section of the monovalent positive ions of the flurbiprofen-beta cyclodextrin-calcium ions, or measuring the ion mobility spectrum of the monovalent positive ions of the flurbiprofen-beta cyclodextrin-calcium ions by using an ion mobility spectrum experimental device, so as to obtain the chiral structure information of the flurbiprofen molecules;
in S2, the flurbiprofen-beta cyclodextrin-calcium ion mixture is in a liquid state or in a solid state prepared from the liquid state according to experimental analysis.
10. The method for the molecular chiral structure analysis of flurbiprofen according to any one of claims 7 to 9, wherein: in S1, the ion source is one of an electrospray ionization ion source, a laser-assisted desorption ionization ion source and a desorption electrospray ionization ion source; in S3, the experimental device is one of an ion mobility spectrometry and a composite experimental device including an ion mobility spectrometry.
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