CN113009028A - Method for detecting related substances of omeprazole sodium for injection - Google Patents
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Abstract
The invention provides a method for detecting related substances of omeprazole sodium for injection, which adopts high performance liquid chromatography to carry out gradient elution on a sample solution, wherein the chromatographic conditions are that a chromatographic column is composed of octane silane bonded silica gel; the detection wavelength is 275-285 nm; the column temperature is 25 +/-1 ℃; the sample injection amount is 18-20 mu l; the flow rate is 0.8-1.1 ml/min; the mobile phase A is 0.01mol/L disodium hydrogen phosphate solution-acetonitrile volume ratio (73-75) to (25-27); the mobile phase B is acetonitrile; the diluent is phosphate buffer solution with pH value of 11.0 plus or minus 0.2 to dilute acetonitrile; the invention optimizes the preparation of the diluent and the mobile phase, combines the optimization of a certain gradient elution program, promotes the full elution of more impurities, and has large separation degree among the impurities and between the impurities and main components, long retention time, high durability of chromatographic columns and instruments, high sensitivity, and good injection precision and repeatability.
Description
Technical Field
The invention relates to the technical field of medicine detection, in particular to a method for detecting related substances of omeprazole sodium for injection.
Background
Omeprazole Sodium (Omeprazole Sodium) belongs to a proton pump inhibitor and has a chemical name: 5-methoxy-2- { [ (4-methoxy-3, 5-dimethyl-2-pyridyl) -methyl ] -sulfinyl } -1H-benzimidazole sodium monohydrate, which is obtained by taking sulfhydryl and pyridine salt as raw materials and carrying out a series of chemical reactions, is a racemic mixture of a pair of active optical antipodes, and has good treatment effect mainly on duodenal ulcer, gastric ulcer, reflux esophagitis, acute gastric mucosal lesion complex ulcer and the like.
Because of poor water solubility of omeprazole, omeprazole is often prepared into a freeze-dried powder injection of omeprazole sodium salt for injection as a main medicinal form, and impurities are easily introduced in the existing production and preparation process of omeprazole sodium for injection, wherein the production of the omeprazole sodium impurities for injection comprises process impurities introduced by raw material omeprazole sodium, degradation impurities generated by the preparation, and the like, so the detection of related substances becomes a key basis for the quality control of the omeprazole sodium preparation, while the existing detection method of related substances of omeprazole sodium for injection is recorded, and the traditional detection method of related substances of raw material medicaments is adopted, and the separation degree among impurities, impurities and main components is low, the single impurity detection limit is high, the sensitivity and the repeatability are poor, and the like, so the detection method of related substances of omeprazole sodium for injection is provided, has important significance for ensuring the safety and the effectiveness of the medicine.
Disclosure of Invention
In view of the above, the invention provides a method for detecting related substances of omeprazole sodium for injection.
The technical scheme of the invention is realized as follows:
the invention provides a method for detecting related substances of omeprazole sodium for injection, which adopts high performance liquid chromatography to carry out gradient elution and analyzes and detects substance impurities in a test solution;
the chromatographic conditions are as follows: a chromatographic column: hichrom Apollo C8, 4.6mm multiplied by 250mm, 5 μm octyl silane bonded silica gel is used as filler; detection wavelength: 275-285 nm; column temperature: 25 +/-1 ℃ of temperature; sample introduction amount: 18-20 mul; the flow rate is 0.8-1.1 ml/min; mobile phase A: the volume ratio of 0.01mol/L disodium hydrogen phosphate solution to acetonitrile (73-75): (25-27), and adjusting the pH value of the sodium dihydrogen phosphate solution to 7.8-7.9 by using phosphoric acid; mobile phase B: acetonitrile;
the diluent is obtained by diluting acetonitrile by using a phosphate buffer solution with the pH value of 11.0 +/-0.2, wherein the volume ratio of the phosphate buffer solution to the acetonitrile is 4 (0.8-1);
the gradient elution was: at 0min, 100% mobile phase a eluted; at 35min, 100% mobile phase a eluted; eluting 68-69% of mobile phase A and 31-32% of mobile phase B at 40 min; eluting 68-69% of mobile phase A and 30-32% of mobile phase B at 60 min; at 60.1min, 100% mobile phase a eluted; at 75min, 100% mobile phase a eluted. The invention optimizes the preparation of the diluent and the mobile phase, combines the optimization of a certain gradient elution program, promotes the full elution of more impurities, has large separation degree among the impurities and between the impurities and main components, long retention time, high durability of chromatographic columns and instruments, high sensitivity, and good injection precision and repeatability
More preferably, the phosphate buffer is prepared by mixing the following components in a mass ratio of 0.34: mixing 0.627 of sodium phosphate dodecahydrate and disodium hydrogen phosphate dodecahydrate, adding water for dissolving and diluting, and adjusting the pH value to 11.0 by using phosphoric acid or 8.5-10 mol/L sodium hydroxide solution.
More preferably, in the mobile phase A, the volume ratio of 0.01mol/L disodium hydrogen phosphate solution to acetonitrile is 73: 27 and the sodium dihydrogen phosphate solution is adjusted to pH 7.8 with phosphoric acid.
More preferably, the 0.01mol/L disodium hydrogen phosphate solution contains triethylamine with the mass concentration of 0.08-0.15%.
More preferably, the concentration of the test sample is 0.5-0.6 mg/ml.
More preferably, the flow rate is 1.0 ml/min.
More preferably, the detection wavelength is 280 nm.
More preferably, the gradient elution is: at 0min, 100% mobile phase a eluted; at 35min, 100% mobile phase a eluted; at 40min, 68.5% mobile phase a and 31.5% mobile phase B eluted; at 60min, 68.5% mobile phase a and 31.5% mobile phase B eluted; at 60.1min, 100% mobile phase a eluted; at 75min, 100% mobile phase a eluted.
Compared with the prior art, the invention has the beneficial effects that:
(1) according to the invention, phosphate buffer solution with pH of 11.0 +/-0.2 is adopted to dilute acetonitrile to be used as a diluent, disodium hydrogen phosphate solution with pH of 7.8-7.9-acetonitrile is used as a mobile phase A and a mobile phase B to be combined, and optimization of a gradient elution program is combined, so that sufficient elution of related substance impurities in a medicine is effectively promoted, the medicine can comprise 13 known impurities, more than 20 total impurities can be contained, each known impurity can reach baseline separation, the separation degree among the impurities and the separation degree between the impurities and a main component are large, and the retention time is long; under the detection wavelength of 275-285 nm, all impurities are greatly absorbed, the related substance detection method is high in sensitivity and good in sample introduction precision and repeatability, meanwhile, the optimization of a mobile phase and an elution program greatly reduces the bacterial growth of the mobile phase, protects a chromatographic column and improves the durability of the chromatographic column and instruments.
Drawings
Fig. 1 is a chromatogram of related substances of omeprazole sodium for injection according to an embodiment of the invention.
Detailed Description
In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.
The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.
The materials, reagents and the like used in the examples of the present invention can be obtained commercially without specific description.
According to the invention, through the analysis of a raw material medicine synthesis process, the known impurity structural formula is as follows:
impurity A: the residual starting material or the degradation of omeprazole sodium is generated under high temperature or acidic condition;
impurity B: the initial material pyridine salt is generated by introducing impurities and carrying out condensation oxidation on the impurities and sulfydryl;
impurity C: condensate residue, generated under acidic or light conditions;
impurity D: oxide is generated through peroxidation, and omeprazole sodium is generated through degradation under an oxidation condition;
impurity E: oxide is generated through peroxidation, and omeprazole sodium is generated through degradation under an oxidation condition;
impurity F: omeprazole sodium is generated by degradation, namely generated under an acidic condition;
impurity G: omeprazole sodium is generated by degradation, namely generated under an acidic condition;
impurity H: reacting the chloro impurities at the methoxy position of the pyridinium with a sulfhydryl compound to generate impurity residues;
impurity I: oxide is generated through peroxidation, and omeprazole sodium is generated through degradation under an oxidation condition;
impurity II: omeprazole sodium degradation impurities are generated by hydrolysis under the high-temperature condition;
impurity III: omeprazole sodium is generated by degradation, namely is generated under the high-temperature condition;
impurity IV: omeprazole sodium is generated by degradation, namely is generated under high temperature or acidic conditions;
impurity VI: the oxide is generated through peroxidation, and the omeprazole sodium is generated through degradation, namely under the oxidation condition.
The results of a forced degradation test of omeprazole sodium for injection, an influence factor test of omeprazole sodium for injection, an acceleration test and a long-term test show that the impurity A is an alkali, thermal and photodegradation product, the impurity C is an acid and photodegradation product, the impurity D is an oxidative degradation product, the impurity II is a light, thermal and alkali degradation product, the impurity III is a thermal degradation product, the impurity IV is a light and thermal degradation product, and the contents of the impurities B, E, F, G and VI are not obviously increased under the current conditions of acid, alkali, oxidation, illumination and high temperature. Namely, the main degradation products of the product are impurity A, impurity C, impurity D, impurity II, impurity III and impurity IV.
Example 1-method for detecting related substances of omeprazole sodium for injection, comprising the following steps:
(1) performing gradient elution on the test solution by adopting a high performance liquid chromatography, wherein the chromatographic conditions are as follows: a chromatographic column: hichrom Apollo C8, 4.6mm multiplied by 250mm, 5 μm octyl silane bonded silica gel is used as filler; detection wavelength: 275 nm; column temperature: 24 ℃; sample introduction amount: 18 mu l of the solution; the flow rate is 0.8 ml/min; mobile phase A:0.01mol/L disodium hydrogenphosphate solution-acetonitrile volume ratio 73: 25, adjusting the pH of the sodium dihydrogen phosphate solution to 7.8 by using phosphoric acid; mobile phase B: acetonitrile;
the diluent is obtained by diluting acetonitrile by using a phosphate buffer solution with pH value of 11.0, and the volume ratio of the phosphate buffer solution to the acetonitrile is 4: 0.8; (the phosphate buffer solution is prepared by mixing sodium phosphate dodecahydrate and disodium hydrogen phosphate dodecahydrate in a mass ratio of 0.34: 0.627, adding water for dissolving and diluting, and adjusting the pH value to 11.0 by adopting phosphoric acid or 8.5mol/L sodium hydroxide solution);
the gradient elution was: at 0min, 100% mobile phase a eluted; at 35min, 100% mobile phase a eluted; at 40min, 68% mobile phase a and 32% mobile phase B eluted; at 60min, 68% mobile phase a and 32% mobile phase B eluted; at 60.1min, 100% mobile phase a eluted; at 75min, 100% mobile phase a eluted;
(2) detecting and analyzing substance impurities in the test solution; the judgment standard is as follows:
and (4) releasing the standard: after the auxiliary material peak is deducted from the chromatogram of the test solution, if a chromatographic peak with the retention time consistent with that of the impurity D exists, the peak area of the chromatographic peak is not larger than the main peak area (0.2%) of the reference solution; if a chromatographic peak with the retention time consistent with that of the impurity II exists, the peak area of the chromatographic peak is not larger than the main peak area (0.2%) of the reference solution; if a chromatographic peak consistent with the retention time of the impurity III exists, the peak area of the chromatographic peak is not larger than the main peak area (0.2%) of the reference solution; if a chromatographic peak consistent with the retention time of the impurity IV exists, the peak area of the chromatographic peak is not larger than the main peak area (0.2%) of the reference solution; the peak area of other single impurities is not more than 0.5 times (0.1%) of the main peak area of the control solution, the sum of the peak areas of the impurities is not more than 5.0 times (1.0%) of the main peak area of the control solution, and less than 0.02% of peaks in the chromatogram of the test solution are ignored;
shelf life standard: after the auxiliary material peak is deducted from the chromatogram of the test solution, if a chromatographic peak with the retention time consistent with that of the impurity D exists, the peak area of the chromatographic peak is not more than 4.5 times (0.9%) of the main peak area of the control solution; if a chromatographic peak with the retention time consistent with that of the impurity II exists, the peak area of the chromatographic peak is not more than 1.5 times (0.3%) of the main peak area of the control solution; if a chromatographic peak consistent with the retention time of the impurity III exists, the peak area of the chromatographic peak is not more than 4.5 times (0.9%) of the main peak area of the control solution; if a chromatographic peak consistent with the retention time of the impurity IV exists, the peak area of the chromatographic peak is not more than 5 times (1.0%) of the main peak area of the control solution; the peak area of other single impurities is not larger than the main peak area (0.2%) of the control solution, and the sum of the peak areas of the impurities is not larger than 7.5 times (1.5%) of the main peak area of the control solution.
Example 2-method for detecting related substances of omeprazole sodium for injection, comprising the following steps:
(1) performing gradient elution on the test solution by adopting a high performance liquid chromatography, wherein the chromatographic conditions are as follows: a chromatographic column: hichrom Apollo C8, 4.6mm multiplied by 250mm, 5 μm octyl silane bonded silica gel is used as filler; detection wavelength: 285 nm; column temperature: 26 ℃; sample introduction amount: 20 mu l of the mixture; the flow rate is 1.1 ml/min; mobile phase A:0.01mol/L disodium hydrogen phosphate solution-acetonitrile volume ratio 75: 27, triethylamine with the mass concentration of 0.08 percent is contained in 0.01mol/L disodium hydrogen phosphate solution, and the pH value of the sodium dihydrogen phosphate solution is adjusted to 7.9 by adopting phosphoric acid; mobile phase B: acetonitrile;
the diluent is obtained by diluting acetonitrile by using a phosphate buffer solution with pH value of 11.0, and the volume ratio of the phosphate buffer solution to the acetonitrile is 4: 1; (the phosphate buffer solution is prepared by mixing sodium phosphate dodecahydrate and disodium hydrogen phosphate dodecahydrate in a mass ratio of 0.34: 0.627, adding water for dissolving and diluting, and adjusting the pH value to 11.0 by adopting phosphoric acid or 10mol/L sodium hydroxide solution);
the gradient elution was: at 0min, 100% mobile phase a eluted; at 35min, 100% mobile phase a eluted; at 40min, 69% mobile phase a and 31% mobile phase B eluted; at 60min, 69% mobile phase a and 31% mobile phase B eluted; at 60.1min, 100% mobile phase a eluted; at 75min, 100% mobile phase a eluted;
(2) the substance impurities in the sample solution were detected and analyzed, and the judgment criteria were as in example 1.
Example 3-method for detecting related substances of omeprazole sodium for injection, comprising the following steps:
a sample to be tested:
comparison products:
step 1: preparing an impurity stock solution: weighing different impurity reference substances, and respectively preparing each impurity stock solution containing 0.1mg of each impurity in each 1ml of solution;
step 2: preparation of system suitability solutions: taking 5mg of omeprazole sodium reference substance, placing the omeprazole sodium reference substance in a 10ml brown measuring flask, precisely adding 0.1ml of each impurity reference substance stock solution, adding a solvent to dilute to a constant volume to scale, and shaking up to be used as a system applicability solution;
and step 3: preparing a test solution, a control solution and a blank auxiliary material solution:
test solution: dissolving the sample to a concentration of 0.5mg/ml as sample solution, and performing photophobic operation for fresh preparation;
control solution: precisely measuring a sample solution lml, placing the sample solution lml in a 100ml measuring flask, diluting the sample solution lml to a scale with a solvent, shaking up, precisely measuring 2ml, placing the sample solution lml in a 10ml measuring flask, diluting the sample solution lml to a scale with a solvent, and shaking up to serve as a control solution;
blank adjuvant solution: precisely weighing 1.5mg of edetate disodium serving as an auxiliary material, placing the precisely weighed edetate disodium in a 20ml measuring flask, adding a solvent to dissolve the edetate disodium, diluting the edetate disodium with the solvent to a scale, shaking up the solution, precisely weighing 5ml of edetate disodium, placing the solution in the 20 measuring flask, diluting the solution with the solvent to the scale, and shaking up the solution to obtain a blank auxiliary material solution;
and 4, step 4: and (3) testing the applicability of the system: precisely measuring 20 mul of system applicability solution, injecting into a liquid chromatograph, determining whether the separation degree between each chromatographic peak meets the specification, and comparing the signal-to-noise ratio of the main peak in the solution to be more than 30;
and 5: and (3) chromatographic determination: precisely measuring 20 mul of each of the test solution and the control solution, and respectively injecting into a liquid chromatograph under the chromatographic conditions: a chromatographic column: hichrom Apollo C8, 4.6mm multiplied by 250mm, 5 μm octyl silane bonded silica gel is used as filler; detection wavelength: 285 nm; column temperature: 25 ℃; sample introduction amount: 20 mu l of the mixture; the flow rate is 1.0 ml/min; mobile phase A:0.01mol/L disodium hydrogenphosphate solution-acetonitrile volume ratio 73: 27, triethylamine with the mass concentration of 0.15 percent is contained in 0.01mol/L disodium hydrogen phosphate solution, and the pH value of the sodium dihydrogen phosphate solution is adjusted to 7.8 by adopting phosphoric acid; mobile phase B: acetonitrile;
the diluent is prepared by dissolving acetonitrile 200ml in phosphate buffer solution (sodium phosphate dodecahydrate 0.34g and disodium hydrogen phosphate dodecahydrate 0.627g in water, diluting to 1000ml, and adjusting pH to 11.0 + -0.2 with phosphoric acid or 10mol/L sodium hydroxide solution) to 1000 m;
the gradient elution was: at 0min, 100% mobile phase a eluted; at 35min, 100% mobile phase a eluted; at 40min, 68.5% mobile phase a and 31.5% mobile phase B eluted; at 60min, 68.5% mobile phase a and 31.5% mobile phase B eluted; at 60.1min, 100% mobile phase a eluted; at 75min, 100% mobile phase a eluted;
recording a chromatogram, and neglecting peaks smaller than 0.02% in the chromatogram of the test solution;
step 6: calculating the formula:
note: a. thei: peak area of a single impurity in a test solution; a. theGeneral assembly: the total peak area in the test solution; a. theMaster and slave: the peak area of the main peak in the test solution; a. theTo pair: peak area of the main peak of the control solution;
and 7: the criteria were as in example 1.
(1) The results of the detection of the substances of interest in the same lot of samples treated under different conditions according to the detection method of example 3 are shown in the following table:
the degradation factor test and detection results in the table show that the impurity A, C, G and the unknown single impurity are only increased under the illumination condition under the conditions of high temperature, high humidity and illumination of the omeprazole sodium for injection; the impurity II is increased under the conditions of high temperature and illumination, the impurities III, IV and D are increased under the conditions of high temperature, and the impurities B, E, F, G and VI are not obviously increased.
(2) The optimization of the method for injecting omeprazole sodium related substances-the system applicability result is shown in the following table,
as can be seen from the table above, all known impurities can achieve baseline separation, the separation degree is high, the retention time is long, and the atlas is shown in figure 1, which shows that the detection method can be effectively used for detecting omeprazole sodium related substances for injection.
Comparative example 1-according to the method for detecting the related substance of omeprazole sodium for injection, it is different from example 3 in that: the gradient elution was: at 0min, 90% mobile phase a and 10% mobile phase B eluted; at 35min, 80% mobile phase a and 20% mobile phase B eluted; at 40min, 68.5% mobile phase a and 31.5% mobile phase B eluted; at 60min, 45.5% mobile phase a and 54.5% mobile phase B eluted; at 75min, 100% mobile phase a eluted, the rest being the same as in example 3; the detection result of the substance impurities in the test solution shows that under the chromatographic condition, the separation degree between the impurities D and B and the main peak and the separation degree between the impurities II and IV are reduced, and the retention time of the impurities II, IV and I is shortened by less than 1.0 min.
In order to verify the detection method of the related substances of the omeprazole sodium for injection, the method verification of the system is carried out, and the method verification comprises the following verification results, wherein the verification results comprise system applicability, specificity, durability, precision, repeatability and the like:
(1) the system applicability is as follows: all chromatographic parameters of the main peak meet the requirements, and the theoretical plate number is 19448 and is more than 2000; the separation degree between every two adjacent impurity peaks in the system applicability solution meets the requirement, and the separation degree between every two impurities and between the impurities and the main component is larger than 1.5.
(2) The specificity is as follows: all known impurities have larger absorption at the selected detection wavelength of 280nm, and are subjected to forced degradation test: omeprazole sodium for injection is unstable and easy to damage under the conditions of oxidative degradation, high-temperature solution, acid degradation and solid illumination, and more impurities are generated; is stable under alkaline conditions and high-temperature solid conditions. Blank auxiliary materials do not interfere with the detection of degradation products; the separation degree between each degradation impurity and the main component peak meets the requirement; the peak purities of the main components are all larger than 0, and the materials are conserved before and after degradation, which shows that the detection method has good specificity.
(3) Durability: when the mobile phase proportion, the flow rate, the column temperature and the pH value of the chromatographic conditions, the chromatographic columns of the same brand and different batches, the chromatographic columns of different brands and different instruments are replaced, compared with the standard conditions, the detection results of various chromatographic parameters in the system applicability solution and the content of impurities in the test sample solution have no obvious difference, the difference value of the detection results of related substances in the test sample solution is +/-0.1%, and the separation degree of all impurities in the system applicability solution is more than 1.5.
(4) Sensitivity: the quantitative limit signal-to-noise ratio S/N is about 10-30; the detection limit signal-to-noise ratio S/N is about 3-7;
(5) sample introduction precision: because the stability of the impurities IV and F, G is poor, the injection precision is not considered, the omeprazole and the quantitative limit solution of each impurity are continuously measured for 6 times, the RSD of the peak retention time of each component is less than 2.0%, and the RSD of the peak area is less than 10.0%, which shows that the injection precision of the detection method is good.
| Name (R) | RTMean value of/min | RSD/％ | AMean value of | RSD/％ |
| Impurity II | 2.386 | 0.16 | 421 | 3.91 |
| Impurity I | 5.265 | 0.49 | 865 | 2.57 |
| Impurity A | 6.940 | 0.35 | 674 | 3.10 |
| Impurity E | 7.751 | 0.29 | 878 | 1.86 |
| Impurity D | 12.653 | 0.73 | 1161 | 2.69 |
| Impurity B | 15.919 | 0.29 | 1672 | 2.97 |
| Omeprazole | 17.672 | 0.30 | 1504 | 6.45 |
| Impurity VI | 22.125 | 0.67 | 2330 | 4.99 |
| Impurity III | 26.633 | 0.21 | 2835 | 2.32 |
| Impurity H | 32.888 | 0.42 | 3061 | 6.90 |
| Impurity C | 45.638 | 0.06 | 598 | 8.07 |
(6) Repeatability: known impurities with various limit concentrations are added into a test solution, 6 samples are tested in parallel, and the RSD of the detected amount of each known impurity is lower than 10.0 percent, which indicates that the detection method has good repeatability.
In conclusion, the systematic method verification results of system applicability, specificity, durability, precision, repeatability and the like show that the method for detecting the related substances of the omeprazole sodium for injection meets the substance detection requirement of the product, and the quality of the product can be effectively evaluated.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (8)
1. A method for detecting related substances of omeprazole sodium for injection is characterized in that: performing gradient elution by high performance liquid chromatography, and analyzing and detecting substance impurities in the sample solution;
the chromatographic conditions are as follows: a chromatographic column: hichrom Apollo C8, 4.6mm multiplied by 250mm, 5 μm octyl silane bonded silica gel is used as filler; detection wavelength: 275-285 nm; column temperature: 25 +/-1 ℃ of temperature; sample introduction amount: 18-20 mul; the flow rate is 0.8-1.1 ml/min; mobile phase A: the volume ratio of 0.01mol/L disodium hydrogen phosphate solution to acetonitrile (73-75): (25-27), and adjusting the pH value of the sodium dihydrogen phosphate solution to 7.8-7.9 by using phosphoric acid; mobile phase B: acetonitrile;
the diluent is obtained by diluting acetonitrile by using a phosphate buffer solution with the pH value of 11.0 +/-0.2, wherein the volume ratio of the phosphate buffer solution to the acetonitrile is 4 (0.8-1);
the gradient elution was: at 0min, 100% mobile phase a eluted; at 35min, 100% mobile phase a eluted; eluting 68-69% of mobile phase A and 31-32% of mobile phase B at 40 min; eluting 68-69% of mobile phase A and 30-32% of mobile phase B at 60 min; at 60.1min, 100% mobile phase a eluted; at 75min, 100% mobile phase a eluted.
2. The method for detecting the related substances of the omeprazole sodium for injection according to claim 1, which is characterized in that: the phosphate buffer solution is prepared from the following components in a mass ratio of 0.34: mixing 0.627 of sodium phosphate dodecahydrate and disodium hydrogen phosphate dodecahydrate, adding water for dissolving and diluting, and adjusting the pH value to 11.0 by using phosphoric acid or 8.5-10 mol/L sodium hydroxide solution.
3. The method for detecting the related substances of the omeprazole sodium for injection according to claim 1, which is characterized in that: in the mobile phase A, the volume ratio of 0.01mol/L disodium hydrogen phosphate solution to acetonitrile is 73: 27 and the sodium dihydrogen phosphate solution is adjusted to pH 7.8 with phosphoric acid.
4. The method for detecting the related substances of the omeprazole sodium for injection according to claim 3, wherein the method comprises the following steps: the 0.01mol/L disodium hydrogen phosphate solution contains triethylamine with the mass concentration of 0.08-0.15%.
5. The method for detecting the related substances of the omeprazole sodium for injection according to claim 1, which is characterized in that: the concentration of the test sample is 0.5-0.6 mg/ml.
6. The method for detecting the related substances of the omeprazole sodium for injection according to claim 1, which is characterized in that: the flow rate was 1.0 ml/min.
7. The method for detecting the related substances of the omeprazole sodium for injection according to claim 1, which is characterized in that: the detection wavelength is 280 nm.
8. The method for detecting the related substances of the omeprazole sodium for injection according to claim 1, which is characterized in that: the gradient elution was: at 0min, 100% mobile phase a eluted; at 35min, 100% mobile phase a eluted; at 40min, 68.5% mobile phase a and 31.5% mobile phase B eluted; at 60min, 68.5% mobile phase a and 31.5% mobile phase B eluted; at 60.1min, 100% mobile phase a eluted; at 75min, 100% mobile phase a eluted.
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