Method for detecting impurity A in amisulpride oral liquid and application thereof
Through high performance liquid chromatography combined with specific derivatization methods, the problem of insufficient sensitivity and accuracy of thin-layer chromatography in detecting impurity A in amisulfuril oral liquid was solved, and high-precision quantitative analysis of impurity A was achieved, which was suitable for quality control and in-depth research of amisulfuril oral liquid.
Patent Information
- Application Number
- CN202411932928.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-26
- Publication Date
- 2025-05-13
AI Technical Summary
When the existing thin layer chromatography (TLC) detects impurity A in amisulfuril oral liquid, the sensitivity and accuracy are insufficient, making it difficult to meet the needs of scientific research fields for high-precision detection, especially in complex sample matrixes, there are problems such as high detection limit, poor selectivity and insufficient reproducibility.
High performance liquid chromatography combined with specific derivatization methods, dansulphonyl chloride was used as the derivatizer, and the pH of the buffer solution was within the range of pH 8.5~pH 11.5. The chromatography column was Agilent ZORBAX Extend C18, the mobile phase was acetonitrile and triethylamine aqueous solution, the flow rate was 0.3ml/min, and was elution was carried out in isometric, with an optimized detection wavelength of 254±5nm. After diluting the sample, quantitative analysis was performed.
The precise quantification analysis of impurity A in amisulfure oral liquid is achieved, with low detection limit, wide linear range, high accuracy and good precision, which is simple and low-cost, suitable for quality control and in-depth research.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of drug detection, and in particular relates to a method for detecting impurity A in amisulpride oral solution and application thereof. Background Art
[0002] Amisulpride is a selective dopamine D2 / D3 receptor antagonist, mainly used to treat schizophrenia and other related mental disorders. During the production and storage of amisulpride oral solution, a certain amount of impurity A may be generated or remain. Its chemical name is N-ethyl-2-aminomethylpyrrolidine and its molecular formula is C7H 16 N2, molecular weight is 128.22, CAS registration number is 26116-12-1, structural formula is Figure 1 shown.
[0003] Since impurity A is not only one of the starting materials in the synthesis process of amisulpride, but also one of the degradation products of amisulpride, the presence or absence of impurity A and its content level are important considerations for the quality control of amisulpride finished products.
[0004] According to the current pharmacopoeia standards, thin layer chromatography (TLC) is recommended to detect impurity A in amisulpride oral solution. However, the TLC method is mainly used for qualitative analysis or semi-quantitative determination, and its sensitivity and accuracy are relatively limited, which cannot fully meet the needs of scientific research for high-precision detection. Especially when dealing with complex sample matrices such as oral liquid preparations, TLC technology is difficult to provide sufficiently accurate quantitative results, which to some extent limits the in-depth study of the formation mechanism of impurity A in amisulpride oral solution and its control strategy.
[0005] Specifically, although TLC, as a simple and cost-effective separation method, performs well in preliminary screening and rapid identification, it has a high detection limit for trace impurities, poor selectivity, and is easily affected by coexisting substances, resulting in deviations in the test results. In addition, since the operating conditions of TLC (such as sample volume, choice of developing agent, etc.) have a great influence on the final results, and these factors vary between different laboratories, the reproducibility and standardization are also lacking. These problems make TLC unsuitable as a scientific research tool that requires high accuracy and repeatability, especially in the pursuit of more stringent quality control standards, the precise quantitative analysis of impurity A in amisulpride oral solution is particularly insufficient. Summary of the invention
[0006] In view of the shortcomings of the prior art, the present invention provides a method for detecting impurity A in amisulpride oral solution and its application. The purpose of the present invention is to develop a more accurate and reliable method for quantitatively analyzing impurity A in amisulpride oral solution.
[0007] The method for detecting impurity A in amisulpride oral solution provided by the present invention comprises the following steps: Step S1: extracting an oral liquid sample containing amisulpride and its potential impurity A; Step S2: mixing the diluted oral liquid sample with the buffer solution and the derivatizing agent solution and performing a heating derivatization reaction to obtain a derivatized mixed solution; Step S3: dilute the derivatization mixture and inject it into high performance liquid chromatography for quantitative analysis.
[0008] As a further optimization scheme, in step S2, the derivatization agent is dansyl chloride; the concentration of the derivatization agent solution is greater than or equal to 5 mg / ml; the pH value of the buffer solution is in the range of pH 8.5 to pH 11.5; the derivatization reaction time is 30 to 180 min; and the temperature of the derivatization reaction is 60±5°C.
[0009] As a further optimization scheme, in step S3, the chromatographic column uses an Agilent ZORBAX ExtendC18 chromatographic column, and the column temperature is controlled in the range of 30-40°C; the mobile phase includes mobile phase A and mobile phase B, mobile phase A is acetonitrile, mobile phase B is a triethylamine aqueous solution with a mass fraction of 0.2±0.05%, and the volume ratio of mobile phase A to mobile phase B is 63:37-67:33; the flow rate of the mobile phase is 0.3±0.05 ml / min.
[0010] As a further optimization scheme, in step S2, the amisulpride oral solution is diluted 50 to 200 times before being used for derivatization, and more preferably, it is diluted 100 times with water before use.
[0011] As a further optimization scheme, in step S2, the buffer solution is a NaHCO3 aqueous solution.
[0012] As a further optimization scheme, in step S2, the volume ratio of the derivatizing agent solution to the buffer solution is 1:0.25~1:2.
[0013] As a further optimization scheme, in step S2, the derivatization solution is an acetone solution of dansyl chloride with a concentration of 7.5-11 mg / ml.
[0014] As a further optimization scheme, in step S3, the liquid chromatography adopts isocratic elution.
[0015] As a further optimization scheme, in step S3, the detection wavelength is set to 254±5 nm.
[0016] As a further optimization scheme, in step S3, the derivatized mixed solution is diluted 3 to 5 times with an aqueous solution of acetonitrile with a volume fraction of 5±1% and then injected into the high performance liquid chromatography.
[0017] The present invention also provides an application of a method for detecting impurity A in amisulpride oral liquid, and the method can be applied to the quality control of amisulpride oral preparations.
[0018] In addition, this method can also be applied to usage scenarios that require higher detection accuracy, such as studying the formation mechanism of impurity A in the drug synthesis pathway; or in pharmacological research to evaluate the impact of impurity A in amisulpride oral solution on human health.
[0019] Beneficial Effects The present invention provides a new method for detecting impurity A in amisulpride oral solution, which adopts high performance liquid chromatography in combination with specific detection conditions and a derivatization method to achieve excellent separation effect. Compared with the method recommended by the current pharmacopoeia, the new method can more accurately quantitatively analyze impurity A in amisulpride oral solution.
[0020] The detection method of the present invention also has the advantages of a wide linear range, low detection limit and quantitative limit, high accuracy and precision, and strong durability.
[0021] The detection method of the present invention is relatively simple to operate, and can adopt an isocratic elution method, effectively reducing detection time and cost, and is suitable for use in a wide range of quality control and in-depth research work. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] Figure 1 It is a structural schematic diagram of the present invention.
[0023] Figure 2 (a) is the HPLC chromatogram of the reference solution.
[0024] Figure 2 (b) is the HPLC chromatogram of the test solution.
[0025] Figure 3 This is the HPLC chromatogram of impurity A in Example 2 after derivatization with dansyl chloride.
[0026] Figure 4 The chromatogram of amisulpride impurity A measured by gas chromatography is shown in Comparative Example 1.
[0027] Figure 5 (a) is the HPLC chromatogram of the reference solution when 2,4-dinitrofluorobenzene was used as the derivatizing agent.
[0028] Figure 5 (b) is the HPLC chromatogram of the test solution when 2,4-dinitrofluorobenzene was used as the derivatizing agent.
[0029] Figure 6 It is the HPLC chromatogram of the test solution in Comparative Example 5.
[0030] Figure 7 The response curve is a graph showing the change in the concentration of the derivatization solution.
[0031] Figure 8 The response curve is as the pH value of the buffer solution changes.
[0032] Fig. 9 The graph is a response graph versus derivative time.
[0033] Fig.10 Response as a function of the volume ratio of derivatization solution to buffer solution.
[0034] Fig.11 This is the linear range experimental result diagram of the detection method.
[0035] Fig.12 This is the experimental result diagram of the quantitative limit and detection limit of the detection method.
[0036] Fig.13 This is a graph showing the accuracy of the detection method.
[0037] Fig.14 This is a graph showing the precision experimental results of the detection method.
[0038] Fig.15 This is a diagram showing the durability test results of the detection method. DETAILED DESCRIPTION
[0039] The present invention is further illustrated by specific examples below. These examples are exemplary and are intended to illustrate the problem and explain the present invention, but are not intended to be limiting.
[0040] Example 1 The impurity A of amisulpride was derivatized and its content was detected by high performance liquid chromatography.
[0041] Preparation of derivatization solution Weigh dansyl chloride into a volumetric flask, add acetone to dissolve and dilute to volume to make a solution containing 10 mg of dansyl chloride per 1 ml.
[0042] Preparation of buffer solution Weigh 5 g of NaHCO3 solid and place it in 100 ml of water, and dissolve it to obtain a buffer solution.
[0043] Preparation of reference stock solution Accurately weigh about 5 mg of the amisulpride impurity AN-ethyl-2-aminomethylpyrrolidine and place it in a 250 ml volumetric flask. Add a 5% by volume acetonitrile aqueous solution to dissolve and make up to volume to obtain a reference stock solution with an amisulpride impurity A content of about 20 µg / ml.
[0044] Preparation of reference solution 5 ml of the reference stock solution was measured and placed in a 50 ml volumetric flask, and an aqueous solution of acetonitrile with a volume fraction of 5% was added to dilute and fix the volume to obtain a diluted reference stock solution, in which the content of amisulpride impurity A was about 2 µg / ml.
[0045] Measure 1 ml of the diluted reference stock solution and place it in a 10 ml volumetric flask, add 1 ml of the derivatization solution, then add 0.5 ml of NaHCO3 buffer solution, and derivatize for 60 min in a 60°C water bath. After cooling, dilute with a 5% acetonitrile aqueous solution to obtain a reference solution, in which the content of amisulpride impurity A is about 0.2 µg / ml.
[0046] Preparation of test solution Accurately measure 1 ml of amisulpride oral solution that does not contain amisulpride impurity A, place it in a 100 ml volumetric flask, dilute it to volume with water and shake it well to obtain an amisulpride content of about 1000 μg / ml; measure 1 ml of the above solution into a 10 ml volumetric flask, add 1 ml of derivatization solution and 0.5 ml of buffer solution respectively, derivatize it in a 60°C water bath for 60 min, take it out and cool it to room temperature, dilute it to volume with an aqueous solution of 5% by volume of acetonitrile to obtain an amisulpride content of about 100 μg / ml.
[0047] Chromatographic conditions Mobile phase A: acetonitrile; Mobile phase B: 0.2% triethylamine aqueous solution; Column: Agilent ZORBAX Extend C18, 4.6 mm, 75 mm, 3.5 µm; Flow rate: 0.3ml / min; Wavelength: 254nm; Column temperature: 35 °C; Injection volume: 20 μl; Isocratic elution: mobile phase A acetonitrile: mobile phase B 0.2% triethylamine aqueous solution = 65:35 V:V.
[0048] Results and Analysis The reference solution and the test solution prepared above were injected and analyzed according to the established chromatographic conditions, and the HPLC chromatogram of the reference solution was obtained as shown in Figure 2 (a) shows the HPLC chromatogram of the test solution. Figure 2 (b) as shown. Figure 2 (a) shows that the retention time of the product derived from impurity A by dansyl chloride is 7.452 min, the peak shape is good, the sensitivity is high, and the minimum separation degree with adjacent peaks is greater than 1.5; Figure 2 (b) shows that the components in amisulpride oral solution have no obvious interference with the elution peak of the derivative product.
[0049] Example 2 On the basis of Example 1, an appropriate amount of impurity A was added as a new test sample during the preparation of the test sample solution, and the test was performed under the same chromatographic conditions.
[0050] Preparation of the test solution in this example: Take 1 ml of amisulpride oral solution, add impurity A, dissolve it in 5% acetonitrile, mix well and then derivatize to make a solution containing 100 μg / ml of amisulpride and 0.5 μg / ml of impurity A per 1 ml.
[0051] The results are as follows Figure 3 As shown, the retention time of the product of impurity A derived from dansyl chloride is 7.467 min, the separation between adjacent peaks is 2.7>1.5, and the tailing factor is 1.1, all of which meet the detection requirements.
[0052] Comparative Example 1 The content of impurity A in amisulpride was determined by gas chromatography.
[0053] Reference to the test method published by Luo Zhuoya et al. References: Luo Zhuoya1, Wang Dongkai2, Li Li3, Lu Zhenghu3. Gas chromatography determination of N-methylpyrrolidine in cefepime hydrochloride [J]. Journal of Pharmaceutical Analysis, 2004, 0(4): 432-433. The impurity AN-ethyl-2-aminomethylpyrrolidine was detected by gas chromatography, and the conditions were optimized according to the characteristics of amisulpride oral solution. The test process is as follows.
[0054] Preparation of impurity A reference solution: Accurately weigh N-ethyl-2-aminomethylpyrrolidine into a volumetric flask and use acetonitrile as solvent to make up to the volume to obtain a 20 µg / mL N-ethyl-2-aminomethylpyrrolidine solution.
[0055] Preparation of the test solution: Accurately measure 1 ml of amisulpride oral solution without amisulpride impurity A and add it into a 5 ml volumetric flask, and dilute to the mark with acetonitrile.
[0056] Set the following instrument conditions: Injector temperature: 200°C; Injection volume: 2µl; Detector temperature: 300°C; Air flow: 300ml / min; Carrier gas: N2; Hydrogen flow rate: 30ml / min; Split ratio: 1:1; Nitrogen flow rate: 30ml / min; Flow rate: 5ml / min; Heating program: constant temperature mode; Chromatographic column: Use DB-35 capillary column with a length of 30m, an inner diameter of 0.32mm, and a film thickness of 1.00µm.
[0057] The prepared impurity A reference solution and test solution were injected into the gas chromatograph for analysis. The results were as follows: Figure 4 As shown, the retention time of impurity A curve a in the reference substance is 11.89 min, the peak area is 10.559, and the response is small; the test solution curve b without impurity A also has a peak near the retention time of 11.89 min. It can be found that the amisulpride oral solution system has a significant interference with the peak of impurity A. If the above-mentioned gas chromatography method is used to detect the content of impurity A in amisulpride oral solution, the specificity and sensitivity cannot meet the detection requirements.
[0058] Comparative Example 2 According to Example 1, only the derivatizing agent dansyl chloride was replaced with 2,4-dinitrophenylhydrazine, and it was found that no peak of any derivatized product could be detected.
[0059] Comparative Example 3 According to Example 1, only the derivatizing agent dansyl chloride was replaced by 2,4-dinitrofluorobenzene.
[0060] Test results such as Figure 5 As shown, Figure 5 (a) is the HPLC chromatogram of the reference solution, showing that the retention time of the product derived from impurity A via 2,4-dinitrofluorobenzene is 8.369 min, the peak shape is good, and the sensitivity meets the requirements. Figure 5 (b) is the HPLC chromatogram of the test solution, showing that the amisulpride oral solution system has an obvious peak at 8.495 min after 2,4-dinitrofluorobenzene derivatization, which cannot be separated from the peak of impurity A. It is found that although the scheme using 2,4-dinitrofluorobenzene derivatization meets the sensitivity requirements, the specificity is poor and it cannot be used in practice.
[0061] Comparative Example 4 The interior of the chromatographic column is filled with stationary phase materials. When the mobile phase carries the sample through the chromatographic column, the different components in the sample interact with the stationary phase and the flow to different degrees, thus achieving separation. Therefore, the chromatographic column has a significant impact on the resolution, peak shape, sensitivity, etc.
[0062] The chromatographic column used in Example 1 was Agilent ZORBAX Extend C18. The results showed that the impurity A had a good peak shape after derivatization, and there was no obvious interference from the active ingredients and excipients in the oral solution. The minimum separation degree with adjacent peaks was greater than 1.5.
[0063] On this basis, we will try to use Waters XTERRA RP 18 chromatographic column and Agilent ZORBAXSB-C18 chromatographic column respectively, and other equipment and operations are consistent with Example 1.
[0064] The results showed that when using the Waters XTERRA RP 18 column, the oral liquid system had interference at the peak position of the derivative product of impurity A and could not meet the specificity requirements; when using the Agilent ZORBAX SB-C18 column, the baseline fluctuated greatly and the repeatability of the test sample was poor.
[0065] The Agilent ZORBAX Extend C18 column used in Example 1, and the Waters XTERRA RP 18 column and Agilent ZORBAX SB-C18 column used in Comparative Example 4 are all reversed-phase C18 columns, and all use a C18 alkyl chain-based stationary phase, but still show significant differences in the derivatization detection system of amisulpride oral solution. Among them, only the Agilent ZORBAX Extend C18 column meets the requirements of separation, specificity and repeatability.
[0066] Comparative Example 5 On the basis of Example 2, the chromatographic conditions were adjusted, wherein the flow rate was adjusted to 1.0 ml / min; mobile phase A acetonitrile: mobile phase B water = 65:35 V:V.
[0067] The test results are as follows Figure 6 As shown, the retention time of the impurity A derivative is 2.113 min, and the peak tailing is severe.
[0068] Example 3 On the basis of Example 1, the derivatization conditions were investigated.
[0069] The concentrations of the derivatized solution were adjusted to 0.2 mg / ml, 0.5 mg / ml, 1 mg / ml, 2 mg / ml, 5 mg / ml, 7.5 mg / ml, 10 mg / ml, and 11 mg / ml, respectively. The response values of the products derived from impurity A by dansyl chloride were as follows: Figure 7 As shown, it indicates that the derivatization solution has a good response when the concentration is greater than or equal to 5 mg / ml, the optimal concentration of the derivatization solution is 7.5-11 mg / ml, and the best is 10 mg / ml.
[0070] The pH values of the buffer solution were adjusted to pH 7.5, pH 8.5, pH 9.0, pH 9.5, pH 10.5, and pH 11.5, respectively. The response values of the products derived from impurity A by dansyl chloride were as follows: Figure 8 As shown, it indicates that the pH value of the buffer solution has a good response in the range of pH 8.5 to pH 11.5, with the best being pH 10.5.
[0071] The derivatization time was adjusted to 30min, 60min, 120min, and 180min, respectively. The response values of the products derived from impurity A by dansyl chloride were as follows: Fig. 9 As shown, it shows that the derivatization time has a good response in the range of 30~180min, and the optimal derivatization time is 60min.
[0072] The volume ratio of the derivatization solution and the buffer solution was adjusted to 1:0.25, 1:0.5, 1:0.75, 1:1, and 1:2. The response values of the products derived from impurity A by dansyl chloride were as follows: Fig.10 As shown, it shows that the ratio has a good response in the range of 1:0.25~1:2.
[0073] Example 4 Based on Example 1 and Example 2, methodological verification was performed.
[0074] 1 Linear range experiment The peak area obtained from each injection was used to perform linear regression analysis on the concentration. The results are as follows: Fig.11 As shown, the linear correlation coefficient is not less than 0.99, the linear intercept percentage is not greater than 25%, and when the concentration of impurity A after derivatization is in the range of 0.05µg / ml~0.75µg / ml0.05%~0.75%, the linear relationship is good and meets the preset acceptance criteria.
[0075] 2 Limit of Quantitation and Limit of Detection The detection limit DL was set as the signal-to-noise ratio of the impurity A derivative peak should be no less than 3; the quantification limit QL was set as the signal-to-noise ratio of the impurity A derivative peak should be no less than 10.
[0076] Test results such as Fig.12As shown, the detection limit was 0.0248µg / ml and the quantification limit was 0.0496µg / ml.
[0077] 3 Limit of Quantitation and Limit of Detection Accuracy Determination: In the presence of excipients and amisulpride, the spiked recovery of impurity A was determined. Concentration levels of 0.05% QL, 0.1%, 0.5%, and 0.75% were selected for accuracy testing.
[0078] Test results such as Fig.13 As shown, at each concentration limit, the average recovery rate of the impurity A derivative ranged from 90% to 110%; the RSD of the recovery rate of the impurity A derivative was 3.1%<25%. The verification results met the preset acceptable standards and the method had good accuracy.
[0079] 4 Precision experiment According to the detection method of impurity A, the test sample solution is spiked with impurity A solution for analysis.
[0080] Test results such as Fig.14 As shown in the figure, in the repeatability test and intermediate precision test, the RSD of the recovery rate of the impurity A derivative in 6 test solutions was 1% and 2%, respectively, both less than 10%; in the repeatability test and intermediate precision test, the RSD% of the recovery rate of the impurity A derivative in 12 test solutions was 3%<20%, and the precision verification results met the preset acceptable standards, indicating that different personnel and different instruments and equipment have little effect on the detection of this method, and the method has good precision.
[0081] 5 Durability Test Robustness evaluates the method's ability to resist interference from variable experimental factors such as chromatographic conditions or mobile phase composition.
[0082] The durability conditions are as follows: Fine-tuning of the mobile phase ratio included: A:B=63:37, A:B=64:36, A:B=67:33; Column temperature fine-tuning includes: 30℃, 40℃.
[0083] Test results such as Fig.15 As shown in the blank solution and excipient solution chromatograms, there was no interference with the detection of impurity A derivatives; in the selective solution and the worst-condition finished product degradation solution, the separation between the impurity A derivative peak and the adjacent peak was ≥1.5; in the test sample spiked solution, under each durability condition, the RSD of the recovery rate of the impurity A derivative was 2%<20%, which met the preset acceptable standard. Verification of the good durability of this method.
[0084] Therefore, through the method validation, the quantitative limit is 0.05%, the detection limit is 0.01%, and the linear relationship is good within 0.05%~1.0% relative to the test sample concentration, and the repeatability and accuracy are good. In addition, compared with other detection methods, this method is simple, low-cost, and uses isocratic elution, which greatly saves detection time and detection costs. At the same time, the method has higher sensitivity and can quantitatively and accurately detect impurity A in amisulpride oral solution.
[0085] The above embodiments are exemplary, and their purpose is to illustrate the technical concept and features of the present invention so that people familiar with the technology in this field can understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.
Claims
1. A method for detecting impurity A in amisulpride oral solution, characterized in that: The following steps are involved: Step S1: extracting an oral liquid sample containing amisulpride and its potential impurity A; Step S2: mixing the diluted oral liquid sample with the buffer solution and the derivatizing agent solution and performing a heating derivatization reaction to obtain a derivatized mixed solution; Step S3: diluting the derivatization mixture and injecting it into a high performance liquid chromatography for quantitative analysis; In step S2, the derivatizing agent is dansyl chloride; The concentration of the derivatization agent solution is greater than or equal to 5 mg / ml; the pH value of the buffer solution is in the range of pH 8.5 to pH 11.5; the derivatization reaction time is 30 to 180 minutes; the derivatization reaction temperature is 60 ± 5 °C; In step S3, the chromatographic column adopts an Agilent ZORBAX Extend C18 chromatographic column, and the column temperature is controlled in the range of 30-40°C; the mobile phase includes mobile phase A and mobile phase B, mobile phase A is acetonitrile, mobile phase B is a triethylamine aqueous solution with a mass fraction of 0.2±0.05%, and the volume ratio of mobile phase A to mobile phase B is 63:37-67:33; the flow rate of the mobile phase is 0.3±0.05 ml / min.
2. The method for detecting impurity A in amisulpride oral solution according to claim 1, characterized in that: In step S2, the amisulpride oral solution is diluted 50 to 200 times and then used for derivatization.
3. The method for detecting impurity A in amisulpride oral solution according to claim 1, characterized in that: In step S2, the buffer solution is a NaHCO3 aqueous solution.
4. The method for detecting impurity A in amisulpride oral solution according to claim 1, characterized in that: In step S2, the volume ratio of the derivatizing agent solution to the buffer solution is 1:0.25-1:
2.
5. The method for detecting impurity A in amisulpride oral solution according to claim 1, characterized in that: In step S2, the derivatization solution is an acetone solution of dansyl chloride with a concentration of 7.5-11 mg / ml.
6. The method for detecting impurity A in amisulpride oral solution according to claim 1, characterized in that: In step S3, the liquid chromatography adopts isocratic elution.
7. The method for detecting impurity A in amisulpride oral solution according to claim 1, characterized in that: In step S3, the detection wavelength is set to 254±5 nm.
8. The method for detecting impurity A in amisulpride oral solution according to claim 1, characterized in that: In step S3, the derivatized mixed solution is diluted 3 to 5 times with an aqueous solution of acetonitrile having a volume fraction of 5±1% and then injected into a high performance liquid chromatograph.
9. Use of the method for detecting impurity A in amisulpride oral solution according to any one of claims 1 to 8, characterized in that: Applied to the quality control of oral amisulpride preparations.
10. Application of the method for detecting impurity A in amisulpride oral solution according to claim 9, characterized in that: Applied to study the formation mechanism of impurity A in drug synthesis pathway; and / or Applied in pharmacological studies to evaluate the effects of impurity A in amisulpride oral solution on human health.