CN115266998A - Method for detecting content of sodium ions in sodium salt molecules - Google Patents
Method for detecting content of sodium ions in sodium salt molecules Download PDFInfo
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- 229910001415 sodium ion Inorganic materials 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 14
- 159000000000 sodium salts Chemical class 0.000 title claims abstract description 14
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 18
- 239000011734 sodium Substances 0.000 claims abstract description 18
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 17
- 239000000243 solution Substances 0.000 claims description 57
- 239000012086 standard solution Substances 0.000 claims description 37
- 238000001514 detection method Methods 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 9
- 238000012360 testing method Methods 0.000 claims description 9
- 150000002500 ions Chemical class 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 238000005341 cation exchange Methods 0.000 claims description 7
- 238000004255 ion exchange chromatography Methods 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 claims description 6
- 238000010812 external standard method Methods 0.000 claims description 6
- 230000014759 maintenance of location Effects 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 230000001629 suppression Effects 0.000 claims description 5
- 230000005484 gravity Effects 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000003480 eluent Substances 0.000 abstract description 13
- 239000000463 material Substances 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
- 238000004458 analytical method Methods 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- 238000012216 screening Methods 0.000 abstract description 2
- UOENJXXSKABLJL-UHFFFAOYSA-M sodium;8-[(2-hydroxybenzoyl)amino]octanoate Chemical compound [Na+].OC1=CC=CC=C1C(=O)NCCCCCCCC([O-])=O UOENJXXSKABLJL-UHFFFAOYSA-M 0.000 description 17
- 239000003085 diluting agent Substances 0.000 description 7
- 230000003252 repetitive effect Effects 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012085 test solution Substances 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000012490 blank solution Substances 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000012372 quality testing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/86—Signal analysis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/86—Signal analysis
- G01N30/8624—Detection of slopes or peaks; baseline correction
- G01N30/8631—Peaks
- G01N30/8637—Peak shape
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N2030/042—Standards
- G01N2030/047—Standards external
Abstract
The invention discloses a method for detecting the content of sodium ions in sodium salt molecules, and relates to the technical field of instrument analysis. The methanesulfonic acid solution is used as the eluent, the chromatographic conditions are regulated by screening the chromatographic column, sodium ions can be well separated on the premise of simple eluent composition, the eluent has high specificity, the sodium ions can be well separated, the peak type is good, no other peak interference exists near the chromatographic peak of the sodium ions, and the sodium content in the sodium salt micromolecule auxiliary material can be accurately detected; the method also has the advantages of good precision, wide linear range, good accuracy and the like, and can well control the product quality.
Description
Technical Field
The invention relates to the technical field of instrument analysis, in particular to a method for detecting the content of sodium ions in sodium salt molecules.
Background
The sodium 8- (2-hydroxybenzamido) caprylate, SNAC for short, is an amino acid derivative absorption enhancer, can promote the oral absorption of various protein drug solutions such as heparin, human growth hormone and the like, can be used for treating gastrointestinal diseases, and has better application prospect.
The content of sodium ions in the product influences the solubility of the product, and the accurate determination of sodium ions in the SNAC is beneficial to accurately judging whether the SNAC is generated, so the accuracy of the determination of sodium ions in the SNAC is related to the quality of the finally obtained medicine.
At present, in the detection method for measuring sodium ions by using the ion chromatography reported in the literature, the used leacheate is complex, has poor specificity and narrow linear range, and is not suitable for analyzing high-concentration elements.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The invention aims to provide a method for detecting the content of sodium ions in sodium salt molecules, aims to test by adopting eluent with simple composition, and has the advantages of high specificity, wide linear range and high precision.
The invention is realized by the following steps:
in a first aspect, the present invention provides a method for detecting the content of sodium ions in sodium salt molecules, comprising:
mixing a sodium element standard solution and a solvent to prepare a standard solution;
mixing a sample to be detected with a solvent to prepare a liquid to be detected;
taking a methane sulfonic acid solution as an eluent, and performing ion chromatography test on a standard solution to determine the retention time of sodium ions and the peak area of the sodium ions in the standard solution;
taking a methanesulfonic acid solution as an eluent, taking a solution to be detected for ion chromatography determination, determining the peak area of sodium ions in the solution to be detected according to the retention time of the sodium ions, and calculating the content of the sodium ions in a sample to be detected according to a formula 1 by adopting an external standard method, wherein the formula 1 is as follows:
in the formula, A S Representing the peak area of sodium ions in the solution to be detected, uS & min;
A T represents the peak area of sodium ions in the standard solution, uS min;
C T the concentration of sodium ions in the standard solution is expressed as mg/mL;
C S indicating the concentration of a sample to be detected in the liquid to be detected, namely mg/mL;
the moisture represents a specific gravity of the moisture in the sample to be measured.
In an alternative embodiment, the solvents used in the preparation of the standard solution, the test solution and the leacheate are all water.
In an alternative embodiment, the concentration of methanesulfonic acid in the leacheate is between 19.6mmol/L and 20.4mmol/L.
In an alternative embodiment, the standard solution has a sodium ion concentration of 0.11mg/mL to 0.13mg/mL.
In an optional embodiment, the concentration of the sample to be detected in the solution to be detected is 1.4 mg/mL-1.6 mg/mL.
In an alternative embodiment, the sample to be tested is sodium 8- (2-hydroxybenzamido) caprylate.
In an alternative embodiment, the chromatographic column of the ion chromatograph is a cation exchange column.
In an alternative embodiment, the cation exchange column is Dionex lonPAC CS 12A, the length of the cation exchange column is 250mm, and the internal diameter is 3mm to 5mm.
In an alternative embodiment, the chromatographic conditions of the ion chromatograph are: the sample introduction volume is 23-27 mu L, the column temperature is 28-32 ℃, the suppression current is 59-63 mA, and the flow rate is 0.9-1.1 mL/min.
In an optional embodiment, at least two standard solutions are used for respective sample injection test, and the F value ratio of the two standard solutions is between 0.98 and 1.02;
wherein the F value is calculated according to equation 2:
the invention has the following beneficial effects: the methanesulfonic acid solution is used as the eluent, the chromatographic conditions are regulated by screening the chromatographic column, sodium ions can be well separated on the premise of simple eluent composition, the eluent has high specificity, the sodium ions can be well separated, the peak type is good, no other peak interference exists near the chromatographic peak of the sodium ions, and the sodium content in the sodium salt micromolecule auxiliary material can be accurately detected; the method also has the advantages of good precision, wide linear range, good accuracy and the like, and can well control the product quality.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIGS. 1 and 2 are chromatograms of a control solution and a solution to be tested in example 1, respectively;
FIG. 3 is a chromatogram of linear solution 6 of example 2;
FIG. 4 is a chromatogram of an intermediate precision 4 solution of example 3;
FIG. 5 is a chromatogram of a test solution of comparative example 1;
FIG. 6 is a chromatogram of a test solution of comparative example 2;
FIG. 7 is a chromatogram of a test solution of comparative example 3.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The embodiment of the invention provides a method for detecting the content of sodium ions in sodium salt molecules, which comprises the following steps:
s1, preparing solution
The solution preparation comprises the preparation of a standard solution, a solution to be detected and a leacheate.
The standard solution is obtained by mixing and diluting a commercially available sodium element standard solution and a solvent, wherein the solvent can be but is not limited to water. The concentration of sodium ions in the standard solution is preferably 0.11 mg/mL-0.13 mg/mL, and may be, for example, 0.11mg/mL, 0.12mg/mL, or 0.13mg/mL.
The solution to be tested is prepared by mixing a sample to be tested and a solvent, wherein the solvent can be but is not limited to water. The concentration of the sample to be detected in the solution to be detected is preferably 1.4 mg/mL-1.6 mg/mL, such as 1.4mg/mL, 1.5mg/mL, 1.6mg/mL, etc. The sample to be detected can be a common sodium salt auxiliary material, such as a common sodium salt auxiliary agent and the like.
In some embodiments, the sample to be detected is sodium 8- (2-hydroxybenzamido) caprylate, referred to as SNAC for short, which is an amino acid derivative absorption enhancer, and the detection method provided in the embodiments of the present invention shows good precision for SNAC detection, and the leacheate is simple and has high specificity and a wide linear range.
The eluent used in the embodiment of the invention is a methanesulfonic acid solution, but is not limited to a methanesulfonic acid aqueous solution, and the concentration of methanesulfonic acid in the eluent is preferably 19.6mmol/L to 20.4mmol/L, and sodium ions can be well separated, specifically 19.6mmol/L, 19.7mmol/L, 19.8mmol/L, 19.9mmol/L, 20.0mmol/L, 20.1mmol/L, 20.2mmol/L, 20.3mmol/L, 20.4mmol/L, and the like.
In some embodiments, the solvents used in the preparation of the standard solution, the solution to be tested and the leacheate are all water, and the water is convenient and feasible, non-toxic and convenient to operate.
S2, detection
Taking a methane sulfonic acid solution as an eluent, and performing ion chromatography test on a standard solution to determine the retention time of sodium ions and the peak area of the sodium ions in the standard solution; taking a methanesulfonic acid solution as an eluent, taking a solution to be detected for ion chromatography determination, determining the peak area of sodium ions in the solution to be detected according to the retention time of the sodium ions, and calculating the content of the sodium ions in a sample to be detected according to a formula 1 by adopting an external standard method, wherein the formula 1 is as follows:
in the formula, A S Representing the peak area of sodium ions in the solution to be detected, uS & min;
A T represents the peak area of sodium ions in the standard solution, uS min;
C T represents the concentration of sodium ions in the standard solution, mg/mL;
C S indicating the concentration of a sample to be detected in the liquid to be detected, namely mg/mL;
the moisture represents the specific gravity of the moisture in the sample to be measured.
It should be noted that the detection method provided by the embodiment of the present invention performs calculation by a conventional external standard method, and the calculation principle is the prior art and is not described herein in detail.
In order to improve the specificity of the detection method of the embodiment of the invention for detecting sodium ions and improve the separation effect of the sodium ions, the inventor optimizes the selection of chromatographic columns and chromatographic conditions:
in some embodiments, the ion chromatograph column is a cation exchange column, which may be Dionex lonPAC CS 12A, having a length of 250mm and an internal diameter of 3mm to 5mm, such as Dionex lonPAC CS 12A 250mm x 4.0mm.
In some embodiments, the chromatographic conditions of the ion chromatograph: the sample introduction volume is 23-27 mu L, the column temperature is 28-32 ℃, the suppression current is 59-63 mA, and the flow rate is 0.9-1.1 mL/min. The detection accuracy is further improved by optimizing the conditions such as sample introduction volume, column temperature, suppression current and flow velocity.
Specifically, the sample injection volume may be 23. Mu.L, 24. Mu.L, 25. Mu.L, 26. Mu.L, 27. Mu.L, etc., the column temperature may be 28 ℃, 29 ℃, 30 ℃, 31 ℃, 32 ℃ etc., the suppression current may be 59mA, 60mA, 61mA, 62mA, 63mA, etc., and the flow rate may be 0.9mL/min, 1.0mL/min, 1.1mL/min, etc.
In order to improve the detection accuracy, at least two standard solutions are used for respective sample injection test, and the F value ratio of the two standard solutions is between 0.98 and 1.02; wherein, the F value is calculated according to formula 2:
it should be noted that the test values of the F values of the two standard solutions are relatively close, and if the ratio exceeds the above range, the test accuracy is not high due to instrument errors, and at this time, the problem needs to be checked and retested.
The features and properties of the present invention are described in further detail below with reference to examples.
In the following examples, all reagents were commercially available unless otherwise specified, and the test methods were carried out according to the conventional test methods.
The instrument comprises the following steps: ion chromatograph (model: dionex Aquion RFIC, brand: thermo, conductivity type detector);
an electronic balance (model: FA1004B, manufacturer: shanghai Yokou instruments Co., ltd.);
reagent: methanesulfonic acid (content: 99%, hadamard reagent Co., ltd.);
sodium element standard solution (1.0 mg/mL, lot number: B21110076, ink quality testing, science and technology Co., ltd.).
Example 1
The embodiment provides a method for detecting the content of sodium ions in sodium salt molecules, which comprises the following specific implementation steps:
(1) Chromatographic conditions
Chromatography column Dionex lonPAC CS 12A 250mm × 4.0mm; the column temperature is 30 ℃; the flow rate is 1.0mL/min; the sample injection volume is 25 mu L; the current was suppressed to 59mA.
(2) Solution preparation
Blank solution: deionized water (Diluent)
Leacheate: 2.6mL of methanesulfonic acid was transferred into 2.0L of deionized water and mixed.
System applicability solution: precisely transferring 6.0mL of sodium standard solution (1.0 mg/mL) into a 50mL measuring flask, adding a diluent to dilute to a constant volume to a scale mark, and shaking up.
Control solution: precisely transferring 6.0mL of sodium standard solution (1.0 mg/mL) respectively, placing the sodium standard solution in two 50mL measuring bottles respectively, adding a diluent respectively to dilute to a constant volume to a scale mark, shaking up, and numbering as follows: control solution 1, control solution 2.
Liquid to be detected: weighing SNAC 74.7mg, placing in a 50mL measuring flask, adding a diluent to dilute to a constant volume to a scale mark, and shaking up.
(3) Detection of
And respectively injecting 25 mu L of blank solution, reference solution and solution to be detected into a liquid chromatograph, and recording the chromatogram.
(4) Formula for calculation
The external standard method calculates formula 1 as follows:
A S representing the peak area of sodium ions in the solution to be detected, uS & min;
A T represents the peak area of sodium ions in the control solution, uS min;
C T the concentration of sodium ions in the control solution is expressed as mg/mL;
C S indicating the concentration of a sample to be detected in the liquid to be detected, namely mg/mL;
the water content represents the specific gravity of the water in the liquid to be detected.
And (4) conclusion: as can be seen from FIGS. 1-2, in the chromatograms of the reference solution and the solution to be detected, the peak patterns of sodium ions are good, and no other chromatographic peak interference exists around the sodium ions. The ratio of the F values of the two control solutions was 1.00 and the sodium content was determined to be 7.63%.
Example 2 Linear test-otherwise, the same as example 1, only the differences from example 1 are described:
within a preset concentration range of 0.024-0.24 mg/mL, a diluent is added to the sodium element standard solution respectively to prepare a series of sodium element linear solutions with sodium ion concentrations of 0.024mg/mL, 0.06mg/mL, 0.09mg/mL, 0.12mg/mL, 0.18mg/mL and 0.24mg/mL, which are respectively marked as linear solutions 1, 2, 3, 4, 5 and 6.
According to the chromatographic conditions in example 1, the linear solutions enter an ion chromatograph, the peak areas and the corresponding concentrations thereof are recorded, regression curves are drawn, and a linear regression equation and regression coefficients are calculated, wherein the linear regression equation is y =263.35x-0.1346, and the correlation coefficient is 0.9998.
And (4) conclusion: the linear relation of the sodium ion is good in the range of 0.024-0.24 mg/mL concentration (20% -200% reference concentration), so that the result of calculating the sodium ion content by using an external standard method in the embodiment is accurate.
The chromatogram for the linear 6 solution is shown in FIG. 3.
Example 3 precision test-other parts are the same as example 1, and only the differences from example 1 are described:
repetitive solution: weighing 6 parts of the SNAC finished product respectively, placing the SNAC finished product in 6 50mL measuring flasks respectively, adding a diluent respectively to dilute to a constant volume until scale marks are formed, and shaking up, wherein the number of the SNAC finished product is respectively repetitive solution 1, repetitive solution 2, repetitive solution 3, repetitive solution 4, repetitive solution 5 and repetitive solution 6.
Change the laboratory technician, on different dates, precision in the middle of different instrument detections, solution preparation: respectively weighing 6 portions of the SNAC finished product, respectively placing the SNAC finished product in 6 50mL measuring flasks, respectively adding a diluent to dilute to a constant volume until a scale mark is formed, and uniformly shaking the SNAC finished product, wherein the number of the SNAC finished product is respectively intermediate precision solution 1, intermediate precision solution 2, intermediate precision solution 3, intermediate precision solution 4, intermediate precision solution 5 and intermediate precision solution 6.
The statistical reproducibility and intermediate precision are 12 parts of data, which are shown in table 1:
TABLE 1 summary of statistical repeatability and intermediate precision data
The chromatogram of the intermediate-precision 4 solution is shown in FIG. 4.
And (4) conclusion: the RSD value of the measured sodium content was 1.89% when 6 parts of the reproducibility data and 6 parts of the intermediate precision data were counted together, so it can be seen that the methods of examples 1 to 3 had good reproducibility and intermediate precision, i.e. good precision and strong feasibility.
Comparative example 1
The difference from example 1 is only that: the flow rate under the chromatographic conditions was 1.3ml/min, and the chromatogram was shown in FIG. 5.
The results show that: the chromatographic peak appears early and slightly tails.
Comparative example 2
The only difference from example 1 is that: the flow rate of the chromatographic conditions was 0.7ml/min, and the chromatogram is shown in FIG. 6.
The results show that: the peak of the chromatographic peak is delayed, and the peak is slightly trailing.
Comparative example 3
Example 1 differs only in that: the leacheate is a mixed solution of methanesulfonic acid and a nitric acid aqueous solution, the volume ratio of the methanesulfonic acid to the nitric acid aqueous solution is 8.
The results show that: other impurity peaks interfere near the main peak, and the impurity peaks are increased, so that the mixed solution may not be suitable for the product of the variety.
In conclusion, the invention provides a method for detecting the content of sodium ions in sodium salt molecules, which uses simple methane sulfonic acid aqueous solution as leacheate to elute SNAC, can well separate the sodium ions contained in the SNAC, has good peak formation, does not interfere near chromatographic peaks, has high specificity, wide linear range and good precision, and can accurately detect the content of sodium in SNAC.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement 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 method for detecting the content of sodium ions in sodium salt molecules is characterized by comprising the following steps:
mixing a sodium element standard solution and a solvent to prepare a standard solution;
mixing a sample to be detected with a solvent to prepare a solution to be detected;
taking a methane sulfonic acid solution as a leacheate, and carrying out ion chromatography test on the standard solution to determine the retention time of sodium ions and the peak area of the sodium ions in the standard solution;
taking the methanesulfonic acid solution as leacheate, taking the solution to be detected for ion chromatography determination, determining the peak area of sodium ions in the solution to be detected according to the retention time of the sodium ions, and calculating the content of the sodium ions in the sample to be detected according to a formula 1 by adopting an external standard method, wherein the formula 1 is as follows:
in the formula, A S Representing the peak area of sodium ions in the solution to be detected, uS & min;
A T represents the peak area of sodium ions in the standard solution, uS min;
C T represents the concentration of sodium ions in the standard solution, mg/mL;
C S indicating the concentration of a sample to be detected in the liquid to be detected, mg/mL;
the moisture represents the specific gravity of the moisture in the sample to be measured.
2. The detection method according to claim 1, wherein the solvents used in the preparation of the standard solution, the solution to be detected and the leacheate are all water.
3. The detection method according to claim 1 or 2, wherein the concentration of methanesulfonic acid in the leacheate is 19.6mmol/L to 20.4mmol/L.
4. The detection method according to claim 1 or 2, wherein the concentration of sodium ions in the standard solution is 0.11mg/mL to 0.13mg/mL.
5. The detection method according to claim 1 or 2, wherein the concentration of the sample to be detected in the solution to be detected is 1.4mg/mL to 1.6mg/mL.
6. The method according to claim 5, wherein the sample to be tested is sodium 8- (2-hydroxybenzamido) caprylate.
7. The detection method according to claim 1, wherein the chromatography column of the ion chromatograph is a cation exchange column.
8. The detection method according to claim 7, wherein the cation exchange column is Dionex lonPAC CS 12A, and the length of the cation exchange column is 250mm and the inner diameter thereof is 3mm to 5mm.
9. The detection method according to claim 8, wherein the chromatographic conditions of the ion chromatograph are: the sample introduction volume is 23-27 mu L, the column temperature is 28-32 ℃, the suppression current is 59-63 mA, and the flow rate is 0.9-1.1 mL/min.
10. The detection method according to claim 1, wherein at least two portions of the standard solution are respectively subjected to sample injection test, and the ratio of the F values of the two portions of the standard solution is between 0.98 and 1.02;
wherein, the F value is calculated according to formula 2:
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