CN115950989A - Related substance analysis method of ebastine oral solution - Google Patents
Related substance analysis method of ebastine oral solution Download PDFInfo
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- CN115950989A CN115950989A CN202310051816.6A CN202310051816A CN115950989A CN 115950989 A CN115950989 A CN 115950989A CN 202310051816 A CN202310051816 A CN 202310051816A CN 115950989 A CN115950989 A CN 115950989A
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- MJJALKDDGIKVBE-UHFFFAOYSA-N ebastine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)CCCN1CCC(OC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MJJALKDDGIKVBE-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 229960001971 ebastine Drugs 0.000 title claims abstract description 46
- 238000004458 analytical method Methods 0.000 title claims abstract description 25
- 229940100688 oral solution Drugs 0.000 title claims abstract description 22
- 239000000126 substance Substances 0.000 title claims abstract description 15
- 239000012535 impurity Substances 0.000 claims abstract description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000007788 liquid Substances 0.000 claims abstract description 9
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 8
- 238000012360 testing method Methods 0.000 claims abstract description 7
- 239000000945 filler Substances 0.000 claims abstract description 6
- 239000008363 phosphate buffer Substances 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 18
- 238000001514 detection method Methods 0.000 claims description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 14
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 claims description 12
- 239000003480 eluent Substances 0.000 claims description 12
- 239000012085 test solution Substances 0.000 claims description 11
- 238000010828 elution Methods 0.000 claims description 10
- HRQDCDQDOPSGBR-UHFFFAOYSA-M sodium;octane-1-sulfonate Chemical compound [Na+].CCCCCCCCS([O-])(=O)=O HRQDCDQDOPSGBR-UHFFFAOYSA-M 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
- 238000007865 diluting Methods 0.000 claims description 7
- DGLRDKLJZLEJCY-UHFFFAOYSA-L disodium hydrogenphosphate dodecahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].OP([O-])([O-])=O DGLRDKLJZLEJCY-UHFFFAOYSA-L 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- AAEQXEDPVFIFDK-UHFFFAOYSA-N 3-(4-fluorobenzoyl)-2-(2-methylpropanoyl)-n,3-diphenyloxirane-2-carboxamide Chemical compound C=1C=CC=CC=1NC(=O)C1(C(=O)C(C)C)OC1(C=1C=CC=CC=1)C(=O)C1=CC=C(F)C=C1 AAEQXEDPVFIFDK-UHFFFAOYSA-N 0.000 claims description 6
- 239000013558 reference substance Substances 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 3
- 230000005526 G1 to G0 transition Effects 0.000 claims description 2
- 238000003556 assay Methods 0.000 claims 2
- 238000010829 isocratic elution Methods 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 15
- 239000003814 drug Substances 0.000 abstract description 15
- 239000000463 material Substances 0.000 abstract description 9
- 238000010521 absorption reaction Methods 0.000 abstract description 6
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 230000014759 maintenance of location Effects 0.000 abstract description 2
- 238000004451 qualitative analysis Methods 0.000 abstract description 2
- 238000004445 quantitative analysis Methods 0.000 abstract description 2
- 230000035945 sensitivity Effects 0.000 abstract description 2
- 239000000523 sample Substances 0.000 description 6
- 239000012488 sample solution Substances 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000008055 phosphate buffer solution Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- JCSTXMWOSJYBFK-UHFFFAOYSA-N C1(=CC=CC=C1)C(C(=O)OO)C.[Na] Chemical compound C1(=CC=CC=C1)C(C(=O)OO)C.[Na] JCSTXMWOSJYBFK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- OQKFGIANPCRSSK-UHFFFAOYSA-N azanium;methanol;acetate Chemical compound [NH4+].OC.CC([O-])=O OQKFGIANPCRSSK-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention belongs to the field of drug analysis, and particularly relates to a related substance analysis method of an ebastine oral solution. The chromatographic column adopting octadecylsilane chemically bonded silica as the filler and phosphate buffer solution-acetonitrile as the mobile phase can effectively separate the auxiliary materials with strong ultraviolet absorption from impurity peaks, enable the peak average of the auxiliary materials to be before the relative retention time of 0.15, avoid interference on the determination of any impurity, and accurately and effectively detect the related substances of the ebastine oral liquid. The method has good specificity, is simple, convenient, rapid, high in sensitivity, good in repeatability and good in accuracy, can be used for rapidly and accurately carrying out qualitative and quantitative analysis on the content of each process impurity and degradation impurity in a test sample, and ensures the controllability of the quality of the product.
Description
Technical Field
The invention belongs to the field of drug analysis, and particularly relates to a method for analyzing related substances of an ebastine oral solution.
Background
Ebastine (Ebastine), chemical name: 1- [4- (1, 1-dimethylethyl) phenyl ] -4- [4- (diphenylmethoxy) -1-piperidyl ] -1-butanone is a group of amine H1 receptor blockers, and is widely used for treating urticaria, allergic rhinitis, eczema and the like.
The ebastine oral solution reference preparation is produced by Spain Eimero medical drug industry Co., ltd, and the prescription contains lactic acid, glycerin, sorbitol, sodium hydroxybenzoate, sodium hydroxy phenylpropionate, sucralose and the like. The ebastine oral solution contains various auxiliary materials with strong ultraviolet absorption besides ebastine, and in the process of stability, specific impurities different from ebastine raw material medicines can be generated.
The national drug standard method adopts a methanol-ammonium acetate buffer solution (pH3.9) as a mobile phase, the detection wavelength is 254nm, but individual impurities are not absorbed under the wavelength, the impurities cannot be effectively separated, and the impurities cannot be accurately detected;
the method described in chinese patent CN102095808 adopts phosphate buffer solution (ph 6.5-10.8) of triethylamine as mobile phase, and has blunt peak shape and trailing, impurities cannot be separated effectively, and impurities cannot be detected completely at preferred wavelength of 250 nm.
Chinese patent CN104101663B discloses a method for detecting related substances in ebastine bulk drug, which can not separate impurities from auxiliary materials.
The existing method can not solve the separation problem of ebastine, each impurity and auxiliary material peak, so the development of the analysis method of related substances of ebastine oral solution is needed.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a method for analyzing related substances of an ebastine oral solution.
The technical scheme of the invention is as follows: a related substance analysis method of ebastine oral solution is a high performance liquid chromatography, which adopts a chromatographic column using octadecylsilane chemically bonded silica as a filler, phosphate buffer as a mobile phase A and acetonitrile as a mobile phase B, wherein the preparation method of the mobile phase A comprises the following steps: 3.58g to 7.16g of disodium hydrogen phosphate dodecahydrate is taken, the pH value is adjusted to 3.0 to 5.0 by phosphoric acid, 1.44g to 2.88g of sodium octane sulfonate is added, dissolved in water and diluted to 1000ml.
In some embodiments, the analytical method performs a linear gradient elution according to the following table:
in the elution process, the sum of the proportion of the mobile phase A and the proportion of the mobile phase B is 100 percent; wherein the proportion of the mobile phase A is the percentage of the volume of the mobile phase A to the total volume of the eluent, and the proportion of the mobile phase B is the percentage of the volume of the mobile phase B to the total volume of the eluent.
In some embodiments, the flow rate of the mobile phase is from 0.9ml to 1.1ml/min; preferably, the flow rate of the eluent is 1.0ml/min.
In some embodiments, the analysis method is performed on a high performance liquid chromatograph, using an ultraviolet detector, and has a detection wavelength of 200nm to 250nm; preferably 210nm.
In some embodiments, the column temperature of the chromatography column is 30 to 40 ℃; preferably 35 deg.c.
In another aspect, the present invention provides a method for analyzing substances related to ebastine oral solution, comprising the steps of:
the analysis method is carried out on a high performance liquid chromatograph; octadecylsilane chemically bonded silica is used as a chromatographic column of a stationary phase;
the analysis method adopts an ultraviolet detector, and the detection wavelength is 210nm;
the column temperature of the analysis method is 30-40 ℃; the sample injection volume is 10 mu l;
the analysis method takes a mobile phase A and a mobile phase B as eluents, wherein the mobile phase A is phosphate buffer, the mobile phase B is acetonitrile, and the mobile phase A is prepared by the following steps: taking 3.58g to 7.16g of disodium hydrogen phosphate dodecahydrate, adjusting the pH value to 3.0 to 5.0 by using phosphoric acid, adding 1.44g to 2.88g of sodium octane sulfonate, dissolving in water, and diluting to 1000ml;
the analytical method was performed with a linear gradient elution according to the following table:
and in the elution process, the sum of the proportion of the mobile phase A and the proportion of the mobile phase B is 100 percent; wherein, the proportion of the mobile phase A is the percentage of the volume of the mobile phase A in the total volume of the eluent, and the proportion of the mobile phase B is the percentage of the volume of the mobile phase B in the total volume of the eluent;
the flow rate of the eluate was 1.0ml/min.
In some specific embodiments, the present invention provides a method for analyzing related substances of an ebastine oral solution, comprising the steps of:
system applicability solution: taking a proper amount of ebastine, impurity A, impurity C and impurity D reference substances, adding acetonitrile-water (50).
Preparing a test solution: taking a proper amount of a test sample, adding acetonitrile-water (50).
Preparation of a control solution: an appropriate amount of the test solution was precisely measured and quantitatively diluted with acetonitrile-water (50).
Octadecylsilane chemically bonded silica is used as a filling agent; taking phosphate buffer solution (3.58 g-7.16 g of disodium hydrogen phosphate dodecahydrate, adjusting the pH value to 3.0-5.0 by using phosphoric acid, adding 1.44 g-2.88 g of sodium octane sulfonate, dissolving in water, dissolving and diluting to 1000 ml) as a mobile phase A, taking acetonitrile as a mobile phase B, and carrying out linear gradient elution according to the following table; the flow rate is 0.9 ml-1.1 ml per minute; the detection wavelength is 210nm; the column temperature is 30-40 deg.C, and the sample injection volume is 10 μ l.
Measuring; and precisely measuring 10 mu l of each of the system applicability solution, the test sample solution and the control solution, respectively injecting into a liquid chromatograph, and recording the chromatogram.
In the present invention, the appropriate amount means that the amount of each compound is within the detection limit or the quantitative limit of the HPLC thereof according to the purpose of the experiment.
The invention has the beneficial effects that: in a test solution, the auxiliary material with strong ultraviolet absorption is effectively separated from impurity peaks, and the peak of the auxiliary material peak is made to be before the relative retention time is 0.15, so that the determination of any impurity is not interfered, and related substances of the ebastine oral liquid can be accurately and effectively detected. In the mobile phase, a proper amount of sodium octane sulfonate is added into the water phase, so that the peak shape is effectively improved, and the peak emergence time of an impurity peak is prolonged, so that the separation degree between the impurity peak and between the impurity peak and the ebastine peak is improved, the method is good in specificity, simple, convenient, rapid, high in sensitivity, good in repeatability and good in accuracy, the qualitative and quantitative analysis of the content of process impurities and degraded impurities in a sample can be rapidly and accurately carried out, and the quality controllability of the product is ensured.
Drawings
FIG. 1 is a diagram of a solution profile for system suitability
FIG. 2 is a test solution map
FIG. 3 is a control solution profile
FIG. 4 is a diagram of the mixture of the blank excipients 1, 2, 3, the impurities A, C, D and ebastine
FIG. 5 is the superposition comparison of the chromatographic chart of ebastine bulk drug detection mixed impurities in European pharmacopoeia and the chromatographic chart of ebastine oral solution test sample solution
FIG. 6 is a comparison of the chromatogram of the detection of mixed impurities in ebastine raw material drug and the blank supplementary material chromatogram of ebastine oral solution in the Japanese pharmacopoeia
FIG. 7 is a graph diagram superposition comparison of CN104101663B mixed impurity solution and ebastine oral solution sample solution for detecting mixed impurity solution
Detailed Description
The following examples are presented to enable those skilled in the art to more fully understand the present invention and are not intended to limit the scope of the present invention.
The impurity A is a starting material in the process of synthesizing the ebastine bulk drug, and is also a degradation impurity, the reference substance is from Sinco, the content is 97.18%, and the structural formula of the impurity is as follows:
impurity C (Chinese pharmacopoeia impurity I) is a reaction byproduct in the process of synthesizing the raw material drug of ebastine, and is also a degradation impurity, the reference substance source is Sinco, the content is 95.83%, and the impurity structural formula is as follows:
the impurity D (Chinese pharmacopoeia impurity II) is an intermediate in the process of synthesizing the ebastine bulk drug, and is also a degradation impurity, the reference substance source is Sinco, the content is 96.07%, and the impurity structural formula is as follows:
EXAMPLE 1 sample testing
System applicability solution: an appropriate amount of ebastine reference substance, impurity A, impurity C and impurity D is taken, and acetonitrile-water (50, V/V) is added for dissolving and diluting to prepare a mixed solution containing approximately 0.5mg ebastine, 1 mu g impurity A, 1 mu g impurity C and 1 mu g impurity D per 1 ml. In the system applicability solution chromatogram, the theoretical plate number is not less than 5000 according to the calculation of an ebastine peak, and the separation degree between an impurity D peak and an impurity C peak meets the requirement.
Test solution: accurately measure 5ml of the product, place the product in a 10ml measuring flask, dilute the product to the scale with acetonitrile-water (50).
Control solution: 1ml of the test solution is precisely measured, placed in a 200ml measuring flask, diluted to the mark with acetonitrile-water (50).
Chromatographic conditions are as follows: octadecylsilane chemically bonded silica is used as a filling agent; taking phosphate buffer solution (3.58 g-7.16 g of disodium hydrogen phosphate dodecahydrate, adjusting the pH value to 3.0-5.0 by using phosphoric acid, adding 1.44 g-2.88 g of sodium octane sulfonate, dissolving in water, dissolving and diluting to 1000 ml) as a mobile phase A, taking acetonitrile as a mobile phase B, and carrying out linear gradient elution according to the following table; the flow rate is 0.9 ml-1.1 ml per minute; the detection wavelength is 210nm; the column temperature is 30-40 ℃, and the sample injection volume is 10 mul.
Measuring; and precisely measuring 10 mul of each of the system applicability solution, the test solution and the control solution, respectively injecting into a liquid chromatograph, and recording the chromatogram.
Comparative example 1: detection method of ebastine bulk drug in European pharmacopoeia
Fig. 5 is a superposition comparison of a chromatogram of ebastine bulk drug detection mixed impurities in european pharmacopoeia and a chromatogram of ebastine oral solution test sample solution, and it can be seen from the figure that 3 strong ultraviolet absorption auxiliary peaks of ebastine oral solution have a large influence on the measurement of impurities, wherein the auxiliary 2 and the impurity 1 almost completely coincide, and the auxiliary 3 and the impurity 2 cannot be completely separated.
Comparative example 2: detection method of ebastine bulk drug in Japanese pharmacopoeia
Fig. 6 is a comparison of the chromatogram of the ebastine raw material drug detection mixed impurities in the japanese pharmacopoeia and the blank ebastine oral solution adjuvant chromatogram, and it can be seen from the graphs that 3 strong uv absorption adjuvant peaks of the ebastine oral solution have a large influence on the determination of the impurities, wherein the adjuvant 1 and the impurity 1 peak almost completely coincide, and the adjuvant 3 and the impurity 2 peak almost completely coincide.
Comparative example 3: CN104101663B detection method
Fig. 7 is a graph superposition comparison of CN104101663B detection mixed impurity solution and ebastine oral solution sample solution, as can be seen from the graph, 3 strong ultraviolet absorption auxiliary material peaks of ebastine oral solution have a large influence on the impurity determination, wherein the auxiliary material 2 and the impurity 1 peak almost completely coincide.
Claims (7)
1. A related substance analysis method of ebastine oral solution is a high performance liquid chromatography, which adopts a chromatographic column using octadecylsilane chemically bonded silica as a filler, phosphate buffer as a mobile phase A and acetonitrile as a mobile phase B, wherein the preparation method of the mobile phase A comprises the following steps: 3.58g to 7.16g of disodium hydrogen phosphate dodecahydrate is taken, the pH value is adjusted to 3.0 to 5.0 by phosphoric acid, 1.44g to 2.88g of sodium octane sulfonate is added, dissolved in water and diluted to 1000ml.
2. The assay of claim 1, wherein the assay performs a linear gradient elution according to the following table:
in the isocratic elution process, the sum of the proportion of the mobile phase A and the proportion of the mobile phase B is 100 percent; wherein the proportion of the mobile phase A is the percentage of the volume of the mobile phase A to the total volume of the eluent, and the proportion of the mobile phase B is the percentage of the volume of the mobile phase B to the total volume of the eluent.
3. The analytical method of claim 1, wherein the flow rate of the mobile phase is 0.9ml to 1.1ml/min; preferably, the flow rate of the eluent is 1.0ml/min.
4. The analytical method according to claim 1, wherein the analytical method is performed on a high performance liquid chromatograph using an ultraviolet detector and the detection wavelength thereof is 200nm to 250nm; preferably 210nm.
5. The analytical method according to claim 1, wherein the column temperature of the chromatographic column is 30 to 40 ℃; preferably 35 deg.c.
6. The analytical method of claim 1, wherein:
the analysis method is carried out on a high performance liquid chromatograph; octadecylsilane chemically bonded silica is used as a chromatographic column of a stationary phase;
the analysis method adopts an ultraviolet detector, and the detection wavelength is 210nm;
the column temperature of the analysis method is 30-40 ℃; the sample injection volume is 10 mu l;
the analysis method takes a mobile phase A and a mobile phase B as eluents, wherein the mobile phase A is phosphate buffer, the mobile phase B is acetonitrile, and the preparation method of the mobile phase A comprises the following steps: taking 3.58g to 7.16g of disodium hydrogen phosphate dodecahydrate, adjusting the pH value to 3.0 to 5.0 by using phosphoric acid, adding 1.44g to 2.88g of sodium octane sulfonate, dissolving in water, and diluting to 1000ml;
the analytical method was carried out with a linear gradient elution according to the following table:
and in the elution process, the sum of the proportion of the mobile phase A and the proportion of the mobile phase B is 100 percent; wherein, the proportion of the mobile phase A is the percentage of the volume of the mobile phase A in the total volume of the eluent, and the proportion of the mobile phase B is the percentage of the volume of the mobile phase B in the total volume of the eluent;
the flow rate of the eluate was 1.0ml/min.
7. A method for analyzing related substances of an ebastine oral solution comprises the following steps:
system applicability solution: taking a proper amount of ebastine, impurity A, impurity C and impurity D reference substances, adding acetonitrile-water (50);
preparing a test solution: taking a proper amount of a test sample, adding acetonitrile-water (50);
preparation of a control solution: precisely measuring a proper amount of a test solution, and quantitatively diluting the test solution with acetonitrile-water (50);
octadecylsilane chemically bonded silica is used as a filling agent; phosphate buffer is used as a mobile phase A, acetonitrile is used as a mobile phase B, wherein the preparation method of the mobile phase A comprises the following steps: taking 3.58g to 7.16g of disodium hydrogen phosphate dodecahydrate, adjusting the pH value to 3.0 to 5.0 by using phosphoric acid, adding 1.44g to 2.88g of sodium octane sulfonate, dissolving in water, and diluting to 1000ml; linear gradient elution was performed according to the following table;
the flow rate is 0.9ml to 1.1ml per minute; the detection wavelength is 210nm; the column temperature is 30-40 ℃, and the sample injection volume is 10 mu l;
measuring; and precisely measuring 10 mul of each of the system applicability solution, the test solution and the control solution, respectively injecting into a liquid chromatograph, and recording the chromatogram.
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