UPLC (Ultra Performance Liquid Chromatography) analysis method of levosalbutamol hydrochloride inhalation solution

Abstract

The invention relates to the technical field of ultra-high performance liquid chromatography, in particular to an ultra-high performance liquid chromatography (UPLC) analysis method of a levosalbutamol hydrochloride inhalation solution. The detection method comprises the following steps: detecting levosalbutamol and related substances in a levosalbutamol hydrochloride inhalation solution; the related substances comprise an impurity A, an impurity B, an impurity C, an impurity D, an impurity E, an impurity F, an impurity G and an impurity H; the detection method adopts ultra-high performance liquid chromatography, and the chromatographic conditions are as follows: octadecylsilane chemically bonded silica is used as a filler; a phosphoric acid aqueous solution with the mass percent of 0.05-0.1% is used as a mobile phase A, and methanol-acetonitrile-water-phosphoric acid is used as a mobile phase B; the detection wavelength is 215 to 225 nm; the column temperature is 40-50 DEG C; the flow velocity is 0.5 to 0.7 mL / min; according to the method, eight impurities can be simultaneously detected and can be effectively separated; the method has the advantages of sensitivity, exclusiveness, accuracy, high efficiency, convenience, low cost and the like, the detection process is completed within 15 minutes, and the efficiency is high. According to the method disclosed by the invention, the contents of the levosalbutamol and the related substances can be effectively controlled, and a basis is provided for quality control of the levosalbutamol hydrochloride inhalation solution, so that the clinical curative effect of the levosalbutamol hydrochloride inhalation solution is ensured.

Description

Technical Field

[0001] The invention relates to the technical field of ultra-high performance liquid chromatography, and in particular to a UPLC analysis method for a levosalbutamol hydrochloride inhalation solution. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Bronchial asthma (abbreviated as asthma) is a common chronic inflammatory disease of the airways of the respiratory system, and its incidence has been increasing year by year in recent years. Currently, the drugs used to treat asthma mainly include β2-adrenergic receptor agonists, glucocorticoids, cholinergic receptor antagonists and leukotriene receptor antagonists. Among them, β2-adrenergic receptor agonists are the most widely used anti-asthma drugs in clinical practice.

[0004] Levalbuterol hydrochloride, chemical name (R)-α 1 -[(tert-Butylamino)methyl]-4-hydroxy-1,3-benzenedimethanol hydrochloride, its chemical structure is as follows:

[0005]

[0006] Salbutamol is a racemic compound consisting of 1:1 ratio of salbutamol and dexalbuterol. It can selectively bind to the β2-adrenergic receptors in the airways, promoting relaxation of airway smooth muscle and dilation of the airways. The affinity of salbutamol for β2-adrenergic receptors is about 100 times that of dexalbuterol, and it is the therapeutically active ingredient of salbutamol. Dexalbuterol can cause immune cell proliferation, cytokine production, and increased calcium ion concentration in airway smooth muscle cells, leading to bronchoconstriction. In addition, compared with salbutamol, dexalbuterol exists longer in the patient's plasma and lung tissue, and is metabolized and eliminated more slowly. When salbutamol is administered as a single isomer, all potential harmful effects of dexalbuterol can be avoided.

[0007] Levosalbutamol hydrochloride solution for inhalation can be administered by nebulization inhalation, allowing the drug to directly enter the airway and be absorbed through the lungs. It has a strong targeting effect, a higher local concentration, a smaller dose required, and fewer systemic adverse reactions. It can also effectively avoid the first-pass effect caused by the liver during oral administration. It is more effective and direct than oral preparations, takes effect more quickly, and has a high bioavailability.

[0008] When levosalbutamol hydrochloride inhalation solution is preserved for a long time, it is easily affected by environmental changes, and the existence form of levosalbutamol in pharmaceutical preparation is changed, and then the therapeutic effect and safe use of medicine are affected. Therefore, the analysis of the related substance of levosalbutamol hydrochloride inhalation solution is most important. At present, the literature report about the related substance analysis method of levosalbutamol hydrochloride inhalation solution is less and all adopts high performance liquid chromatography (HPLC), and the analysis time is long, and efficiency is low. Summary of the invention

[0009] In order to overcome the deficiencies in the prior art, the purpose of the present invention is to provide a UPLC analysis method for a salbutamol hydrochloride inhalation solution, wherein the method of the present invention can simultaneously detect 8 impurities and can effectively separate them; the method has the advantages of being sensitive, exclusive, accurate, efficient, convenient, and low-cost, and the detection process is completed within 15 minutes with high efficiency. The content of salbutamol and related substances can be effectively controlled by the method of the present invention, providing a basis for the quality control of the salbutamol hydrochloride inhalation solution, thereby ensuring its clinical efficacy.

[0010] Specifically, the present invention is achieved through the following technical solutions:

[0011] In a first aspect of the present invention, the present invention provides a UPLC analysis method for a levosalbutamol hydrochloride inhalation solution, the detection method comprising detecting levosalbutamol and related substances in the levosalbutamol hydrochloride inhalation solution; the related substances are impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H;

[0012] The detection method adopts ultra-high performance liquid chromatography, and the chromatographic conditions are: using octadecylsilane bonded silica gel as a filler; using a phosphoric acid aqueous solution with a mass percentage of 0.05-0.1% as a mobile phase A, and using methanol-acetonitrile-water-phosphoric acid as a mobile phase B; the detection wavelength is 215-225nm; the column temperature is 40-50°C; the flow rate is 0.5-0.7mL / min; and gradient elution is performed according to the following table;

[0013] Time / min Mobile phase A / % Mobile phase B / % 0 100 0 7.2 70 30 12 28 72 12.01 0 100 13 0 100 13.01 100 0 15 100 0

[0014] Preferably, the mobile phase A is prepared by diluting phosphoric acid with water to obtain the mobile phase A.

[0015] Preferably, the mobile phase B is methanol-acetonitrile-water-phosphoric acid, the phosphoric acid is calculated as 85% by mass, and the volume ratio of methanol, acetonitrile, water and phosphoric acid is 350:345-355:295-305:0.5-1.5.

[0016] Preferably, the mobile phase B is prepared by mixing 350 ml of methanol, 350 ml of acetonitrile and 300 ml of water, and then adding 1 ml of phosphoric acid and mixing well to form the mobile phase B.

[0017] Preferably, the method includes providing a test solution, wherein the preparation method of the test solution includes: taking a salbutamol hydrochloride inhalation solution, diluting it with a diluent to obtain a sample solution of a set concentration (generally 100 μg / ml, calculated as salbutamol hydrochloride), filtering, and taking the filtrate as the test solution.

[0018] Further preferably, the preparation method of the test solution comprises: taking a salbutamol hydrochloride inhalation solution, adding a diluent, vortexing to obtain a sample solution of a set concentration, filtering, and using the filtrate as the test solution. Specifically, the volume ratio of the salbutamol hydrochloride inhalation solution to the diluent is 1:1.2 to 1.8.

[0019] More preferably, the diluent is a 0.9% sodium chloride aqueous solution with a pH of 3.3 to 4.5.

[0020] Further preferably, the diluent is prepared by dissolving sodium chloride in water, adjusting the pH to 3.3-4.5 with sulfuric acid, and diluting the volume with water.

[0021] Further preferably, the diluent is prepared by taking 9.0 g of sodium chloride, adding 950 ml of water, adjusting the pH to 4.0 with sulfuric acid, and making the volume to 1000 ml with water, and using the solution as the diluent.

[0022] Preferably, the method comprises providing a system suitability solution, wherein the preparation method of the system suitability solution comprises: accurately weighing reference substances of levosalbutamol hydrochloride, impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H, dissolving them, mixing and diluting them to prepare the system suitability solution.

[0023] Further preferably, the method for preparing the system suitability solution comprises: accurately weighing salbutamol hydrochloride, impurity A, impurity B, impurity C, impurity D, impurity E, impurity G and impurity H reference substances and dissolving them with a diluent, and dissolving impurity F with an acetonitrile aqueous solution (the volume concentration may be 55-65%); mixing and diluting to prepare a system suitability solution containing 100 μg / mL of salbutamol hydrochloride and 0.05 μg / mL of each impurity.

[0024] Preferably, the method comprises providing a sensitivity test solution, wherein the preparation method of the sensitivity test solution comprises: accurately weighing a levosalbutamol hydrochloride reference substance, dissolving it, and then diluting it to prepare the sensitivity test solution.

[0025] Further preferably, the preparation method of the sensitivity test solution comprises: accurately weighing the salbutamol hydrochloride reference substance, dissolving it in a diluent, and then diluting it to prepare a sensitivity test solution of a set concentration (which may contain 0.05 μg / mL of salbutamol hydrochloride).

[0026] Preferably, in the chromatographic conditions of the method, the detection wavelength is 210 nm; the column temperature is 45° C.; and the flow rate is 0.6 ml / min.

[0027] Preferably, in the chromatographic conditions of the method, the specifications of the chromatographic column are 2.1×100 mm, 1.7 μm.

[0028] Preferably, the method further comprises the step of detecting related substances of the levosalbutamol hydrochloride inhalation solution, and the step of detecting related substances comprises: providing a system suitability solution, a sensitivity test solution and a test solution, and sequentially taking the system suitability solution, the sensitivity test solution and the test solution for analysis in ultra-high performance liquid chromatography, wherein the system suitability solution, the sensitivity test solution and the test solution are analyzed in ultra-high performance liquid chromatography using octadecylsilane bonded silica gel as a filler; using 0.05-0.1% phosphoric acid aqueous solution as mobile phase A, and using methanol-acetonitrile-water-phosphoric acid (35:35:30:0.05-0.1) as mobile phase B; the detection wavelength is 218-222nm; the column temperature is 40-50°C; the flow rate is 0.5-0.7mL / min; and gradient elution is performed according to Table 1. The separation between salbutamol and impurity A in the system suitability solution chromatogram is not less than 4.9, the separation between impurity B and impurity C is not less than 1.5, and the tailing factor of the salbutamol peak is not greater than 4.0. The signal-to-noise ratio in the sensitivity test solution chromatogram is not less than 10.

[0029] Preferably, analyzing and detecting the system suitability solution, sensitivity test solution and test solution in liquid chromatography includes: injecting 10 μL of the system suitability solution, sensitivity test solution and test solution into a chromatograph, analyzing for 15 min, and recording a chromatogram.

[0030] Preferably, the detection method further comprises calculating the impurity content by area normalization method.

[0031] The present invention provides a UPLC analysis method for a levosalbutamol hydrochloride inhalation solution. The advantages of using the impurity detection method of the present invention are:

[0032] The present invention carries out a large number of screening experiments on mobile phases and elution modes, and the results show that when the mobile phase and elution mode as described above are used, the present invention is more suitable for the detection and analysis of related substances of the levosalbutamol hydrochloride inhalation solution of the present invention, and when the mobile phase and elution mode of the present invention are used, under the conditions of changing the wavelength (215nm, 220nm, 225nm), column temperature (40℃, 45℃, 50℃), flow rate (0.5ml / min, 0.6ml / min, 0.7ml / min), and changing the amount of phosphoric acid added in the mobile phase (0.5ml, 1ml, 1.5ml), the system applicability parameters all meet the requirements, and the method has good durability.

[0033] The present invention has been found in practice that when the method of the present invention is used to detect the above-mentioned salbutamol hydrochloride inhalation solution, the related substances produced after light, high temperature, strong acid, strong alkali, and oxidation damage can be well separated from the main component, and the method has good specificity.

[0034] The detection method provided by the invention can quickly and effectively control the content of related substances of levosalbutamol hydrochloride inhalation solution, provide a basis for quality control of levosalbutamol hydrochloride inhalation solution, thereby ensuring its clinical efficacy. The main related substances and main components of the detection method of levosalbutamol hydrochloride inhalation solution can be well separated, and the main impurity peaks are completely separated.

[0035] The chemical structures of the impurities are as follows:

[0036] Impurity A:

[0037]

[0038] Impurity B:

[0039]

[0040] Impurity C:

[0041]

[0042] Impurity D:

[0043]

[0044] Impurity E:

[0045] Impurity F:

[0046] Impurity H:

[0047] Impurity G:

[0048] BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0050] Figure 1 is the blank solvent spectrum of Example 1 of the present invention;

[0051] Figure 2 This is the system applicability solution spectrum of Example 1 of the present invention. DETAILED DESCRIPTION

[0052] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0053] Example 1: Specificity

[0054] 1-1 Solution Preparation

[0055] Blank solvent (diluent): Take 9.0g of sodium chloride, add 950ml of water, adjust the pH to 4.0 with sulfuric acid, and make up to 1000ml with water.

[0056] System suitability solution: Accurately weigh levosalbutamol hydrochloride, impurity A, impurity B, impurity C, impurity D, impurity E, impurity G and impurity H reference substances and dissolve them in diluent, dissolve impurity F in 60% acetonitrile, mix and dilute to prepare a system suitability solution containing 100 μg / mL of levosalbutamol hydrochloride and 0.05 μg / mL of each impurity.

[0057] Sensitivity solution: Accurately weigh the salbutamol hydrochloride reference substance, dissolve it in the diluent, and then dilute it to make a sensitivity test solution containing 0.05 μg / mL of salbutamol hydrochloride.

[0058] Test solution: Take 2 ml of salbutamol hydrochloride inhalation solution, place it in a centrifuge tube, add 3 ml of diluent, vortex mix to obtain a sample solution with a concentration of about 100 μg / ml, filter, and use the filtrate as the test solution.

[0059] 1-2 Chromatographic conditions

[0060] Chromatographic column: a chromatographic column with octadecylsilane bonded silica as filler; 0.1% phosphoric acid aqueous solution as mobile phase A, methanol-acetonitrile-water-phosphoric acid (35:35:30:0.1) as mobile phase B; detection wavelength of 220 nm; column temperature of 45°C; flow rate of 0.6 mL / min; gradient elution according to Table 1.

[0061] Table 1 Gradient elution

[0062] Time (min) Mobile phase A (%) Mobile phase B (%) 0 100 0 7.2 70 30 12 28 72 12.01 0 100 13 0 100 13.01 100 0 15 100 0

[0063] The preparation method of mobile phase A is as follows: take 1g of phosphoric acid and dilute it to 1000g with water as mobile phase A.

[0064] The preparation method of mobile phase B is as follows: take 350 ml of methanol, 350 ml of acetonitrile and 300 ml of water, mix them evenly, then add 1 ml of phosphoric acid (mass fraction is 85%) and mix well to use as mobile phase B.

[0065] 1-3 Conclusion

[0066] Accurately measure the above solution, inject it into the ultra-high performance liquid chromatograph, and record the chromatogram. The results are shown in Table 2, and the blank solvent spectrum is shown in Figure 1 , system suitability solution spectrum see Figure 2 .

[0067] Table 2 System suitability solution results

[0068]

[0069]

[0070] Conclusion: The blank solvent does not interfere with the separation and detection of the main component and each impurity; the order of the peaks of each component in the system suitability solution is impurity G, salbutamol hydrochloride, impurity A, H, B, C, D, E and F, the separation between each chromatographic peak is greater than 1.5, the separation between salbutamol and impurity A is greater than 4.9, and the tailing factor of the salbutamol peak is less than 4.0, which meets the system suitability requirements. The signal-to-noise ratio of the main component peak height of the sensitivity solution is 112, which is greater than 10 and meets the requirements. It shows that the method of the present invention has good specificity and high detection sensitivity.

[0071] Example 2: Strong degradation test

[0072] 2-1 Strong degradation test conditions

[0073] The blank solvent and the salbutamol hydrochloride inhalation solution were subjected to acid, alkali, oxidation, high temperature and light destruction respectively. The strong degradation test conditions are as shown in Table 3:

[0074] Table 3 Strong degradation test conditions

[0075]

[0076]

[0077] 2-2 Chromatographic conditions are the same as those in Example 1.

[0078] 2-3 Conclusion

[0079] Accurately measure the above solution, inject it into ultra-high performance liquid chromatography, record the chromatogram, and the results are shown in Table 4.

[0080] Table 4 Strong degradation test results

[0081]

[0082] Conclusion: Under each degradation condition, the main peak purity was qualified and the materials were conserved. Under each degradation condition, the blank solvent did not interfere with the detection of related substances. The separation between the main peak and the impurity A peak was greater than 4.9, the minimum separation between the known impurities and the adjacent impurity peaks was greater than 1.5, and the main peak tailing factor was less than 4.0, indicating that the method of the present invention can effectively detect the degradation products in the product and has good method specificity.

[0083] Example 3: Linearity and Range

[0084] 3-1 Solution preparation

[0085] Accurately weigh appropriate amounts of each impurity reference substance and levosalbutamol reference substance, and prepare a series of linear solutions with concentrations ranging from the quantitative limit to 200%.

[0086] 3-2 Chromatographic conditions are the same as those in Example 1.

[0087] 3-3 Conclusion

[0088] The above solution was accurately measured and injected into the ultra-high performance liquid chromatograph to record the chromatogram. The results are shown in Table 5. A linear regression equation was made with the concentration as the abscissa and the peak area as the ordinate.

[0089] Table 5 Summary of linearity and range results

[0090] Element Linear range (μg / mL) Correlation coefficient r Levosalbutamol 0.009～0.178 0.9999 Impurity A 0.005～0.176 0.9999 Impurity B 0.007～0.175 0.9998 Impurity C 0.006～0.167 0.9999 Impurity D 0.005～0.162 1.0000 Impurity E 0.008～0.173 0.9997 Impurity F 0.009～0.186 0.9999 Impurity G 0.008～0.156 0.9999 Impurity H 0.006～0.169 0.9996

[0091] Conclusion: The linear relationship of each impurity is good within the measurement range, meeting the linearity and range detection requirements.

[0092] Example 4: Limit of Quantitation and Limit of Detection

[0093] 4-1 Solution preparation

[0094] Accurately weigh appropriate amounts of levosalbutamol hydrochloride reference substance, impurity A, B, C, D, E, F, G and H reference substances, and use blank solvent to prepare a solution with a signal-to-noise ratio that meets the requirements.

[0095] 4-2 Chromatographic conditions are the same as those in Example 1.

[0096] 4-3 Conclusion

[0097] Accurately measure the above solution, inject it into ultra-high performance liquid chromatography, record the chromatogram, and the results are shown in Table 6.

[0098] Table 6 Results of limit of quantitation and limit of detection

[0099]

[0100] Conclusion: The quantitative limits of each impurity are lower than the impurity reporting limit of this product (0.05%). The detection limit and quantitative limit of this method meet the requirements for quantitative detection of each impurity in the test sample, indicating that the detection sensitivity of the method of the present invention is high.

[0101] Example 5: Accuracy Experiment

[0102] The accuracy was investigated through recovery test, and the study covered the limit concentration range of 50% to 150%.

[0103] 5-1 Solution preparation

[0104] Background solution: Prepare the test solution in the same way as in Example 1.

[0105] Recovery solution: Prepare spiked recovery solutions containing 50%, 100% and 150% of each impurity concentration, and prepare 3 replicates for each concentration.

[0106] 5-2 Chromatographic conditions are the same as those in Example 1.

[0107] 5-3 Conclusion:

[0108] Accurately measure the above solution, inject it into ultra-high performance liquid chromatography, record the chromatogram, and calculate the accuracy by peak area according to the external standard method. The results are shown in Table 7.

[0109] Table 7 Accuracy test results

[0110]

[0111]

[0112]

[0113]

[0114]

[0115] Conclusion: Under 50%, 100% and 150% accuracy solutions, the average recoveries and RSDs of impurities A, B, C, D, E, F, G and H all met the requirements, indicating that the method of the present invention has good accuracy.

[0116] Example 6: Precision Experiment

[0117] 6-1 Solution preparation

[0118] Test solution: Prepare 6 solutions in parallel according to the 100% recovery solution in Example 5.

[0119] The above operations were performed by two experimenters respectively.

[0120] 6-2 Chromatographic conditions are the same as those in Example 1.

[0121] 6-3 Conclusion:

[0122] Accurately measure the above solution, inject it into ultra-high performance liquid chromatography, record the chromatogram, and calculate the impurity content.

[0123] Conclusion: The maximum RSD value of each impurity in the 6 parallel prepared test sample (spiked) solutions was 2.6%, which was less than 3.0%; the maximum RSD value of each impurity in the 12 parallel prepared test sample (spiked) solutions was 3.8%, which was less than 5.0%, which proved that the method of the present invention has good precision.

[0124] Example 7: Durability Test

[0125] Durability refers to the degree to which the test results are not affected by slight changes in the chromatographic conditions. The system suitability solution is the same as that of Example 1. On the basis of the test conditions of Example 1, the durability of the test method is investigated by changing the wavelength, flow rate, column temperature and phosphoric acid addition amount. The test results are shown in Table 8.

[0126] Table 8 Durability system suitability results

[0127]

[0128]

[0129]

[0130] Conclusion: When changing (wavelength, column temperature, flow rate, phosphoric acid addition amount), the impurity separation degree and tailing factor in the system applicability solution meet the requirements, and the technical solution provided by the present invention has good durability.

[0131] Based on the above experimental results, the detection method of the present invention is used to detect the levosalbutamol hydrochloride inhalation solution, and the main related substances and the main components can be well separated, and the main impurity peaks are completely separated, and a significantly higher impurity detection rate is obtained. The method of the present invention is sensitive, exclusive, accurate, efficient, convenient, fast, and low-cost, and can provide a basis for the quality control of the levosalbutamol hydrochloride inhalation solution, thereby ensuring its clinical efficacy.

[0132] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A UPLC analysis method for salbutamol hydrochloride inhalation solution, characterized in that: The detection method comprises detecting levosalbutamol and related substances in a levosalbutamol hydrochloride inhalation solution; the related substances are impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H; The detection method adopts ultra-high performance liquid chromatography, and the chromatographic conditions are: using octadecylsilane bonded silica gel as a filler; using a phosphoric acid aqueous solution with a mass percentage of 0.05-0.1% as a mobile phase A, and using methanol-acetonitrile-water-phosphoric acid as a mobile phase B; the detection wavelength is 215-225nm; the column temperature is 40-50°C; the flow rate is 0.5-0.7mL / min; and gradient elution is performed according to the following table; 。 2. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 1, characterized in that: The mobile phase A is prepared by diluting phosphoric acid with water to obtain the mobile phase A.

3. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 1, characterized in that, The mobile phase B is methanol-acetonitrile-water-phosphoric acid, the phosphoric acid is calculated as 85% by mass, and the volume ratio of methanol, acetonitrile, water and phosphoric acid is 350:345-355:295-305:0.5-1.

5.

4. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 1, characterized in that: The method comprises providing a test solution, wherein the preparation method of the test solution comprises: taking a levosalbutamol hydrochloride inhalation solution, diluting it with a diluent to obtain a sample solution of a set concentration, filtering it, and taking a subsequent filtrate as the test solution.

5. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 4, characterized in that: The preparation method of the test solution comprises: taking a salbutamol hydrochloride inhalation solution, adding a diluent, vortexing and mixing to obtain a sample solution of a set concentration, filtering, and using the filtrate as the test solution; preferably, the volume ratio of the salbutamol hydrochloride inhalation solution to the diluent is 1:1.2-1.8; Or, it is characterized in that the diluent is a 0.9% sodium chloride aqueous solution with a pH of 3.3 to 4.5; Alternatively, the diluent may be prepared by dissolving sodium chloride in water, adjusting the pH value to 3.3-4.5 with sulfuric acid, and diluting the volume with water.

6. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 1, characterized in that: The method includes providing a system suitability solution, wherein the preparation method of the system suitability solution includes: accurately weighing reference substances of levosalbutamol hydrochloride, impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H, dissolving them, mixing and diluting them to prepare the system suitability solution; Preferably, the method for preparing the system suitability solution comprises: accurately weighing levosalbutamol hydrochloride, impurity A, impurity B, impurity C, impurity D, impurity E, impurity G and impurity H reference substances and dissolving them with a diluent, and dissolving impurity F with an acetonitrile aqueous solution.

7. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 1, characterized in that: The method comprises providing a sensitivity test solution, wherein the preparation method of the sensitivity test solution comprises: accurately weighing a levosalbutamol hydrochloride reference substance, dissolving it, and then diluting it to prepare the sensitivity test solution. Further preferably, the method for preparing the sensitivity test solution comprises: accurately weighing the levosalbutamol hydrochloride reference substance, dissolving it in a diluent, and then diluting it to prepare a sensitivity test solution of a set concentration.

8. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 1, characterized in that: In the chromatographic conditions of the method, the detection wavelength is 210 nm; the column temperature is 45° C.; the flow rate is 0.6 ml / min; Or, in the chromatographic conditions of the method, the specifications of the chromatographic column are 2.1×100 mm, 1.7 μm.

9. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 1, characterized in that: The system suitability solution, the sensitivity test solution and the test solution are analyzed and tested in the liquid chromatography, including: injecting 10 μL of the system suitability solution, the sensitivity test solution and the test solution into the chromatograph, the analysis time is 15 minutes, and the chromatogram is recorded.

10. The UPLC analysis method of the salbutamol hydrochloride inhalation solution as claimed in claim 1, characterized in that: The detection method also includes calculating the impurity content by area normalization method.

Images