Method for detecting chlorinated impurities in lurasidone hydrochloride raw material

Abstract

The invention belongs to the field of pharmaceutical analysis, and relates to a method for detecting chlorinated impurities in a lurasidone hydrochloride raw material. Comprising the following steps: dissolving a lurasidone hydrochloride raw material with formic acid and acetonitrile, adding water for dilution, carrying out ultrasonic precipitation, and filtering to obtain a test solution; wherein the volume ratio of the formic acid to the acetonitrile to the water is (0.9-1.1): (8-10): (85-95); and detecting the test solution by adopting high performance liquid chromatography to obtain the content of the chlorinated impurities in the lurasidone hydrochloride raw material. The detection method is accurate and reliable in result, simple and convenient to operate, high in precision and good in precision and linearity, the problem that lurasidone hydrochloride is not easy to dissolve can be effectively solved, and 40 mg / ml of lurasidone hydrochloride can be dissolved to the maximum extent. The detection method provided by the invention provides a vacancy of a chlorinated impurity detection method, and can be applied to production quality control of lurasidone hydrochloride raw material medicines.

Description

Technical Field

[0001] The invention belongs to the field of drug analysis and relates to a method for detecting chlorinated impurities in lurasidone hydrochloride raw materials. 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] Lurasidone hydrochloride is a central dopamine D2 (DRD2) and 5-hydroxytryptamine (5-HT2A) receptor antagonist used to treat schizophrenia and bipolar disorder type I (bipolar depression). Its chemical structure is shown below:

[0004]

[0005] During its preparation, lurasidone hydrochloride can produce chlorinated impurities as byproducts. Currently, none of the public standards control this impurity, and its content directly affects the product quality. At the same time, chlorinated impurities are genotoxic impurities with low limit requirements. They are generally analyzed by mass spectrometry, which is costly and difficult to operate. The production process is as follows: (R,R)-1,2-bis(methylsulfonyloxymethyl)cyclohexane and 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride react to generate 4-(1,2-benzisothiazole-3-yl)-piperazin-1-yl-1,1-dimethyl[(R,R)-1,2-yl]cyclohexane methanesulfonate. The chemical structure of the chlorinated impurity is as follows:

[0006]

[0007] Therefore, it is necessary to establish corresponding quality control methods for the above-mentioned chlorinated impurities and perform quality control on them as specific impurities to further improve the quality of raw materials. Summary of the invention

[0008] In order to solve the deficiencies of the prior art, the purpose of the present invention is to provide a method for detecting chlorinated impurities in lurasidone hydrochloride raw materials. The present invention adopts high performance liquid chromatography (HPLC) to achieve its detection, and the instruments used are all universal, with low detection cost and simple operation.

[0009] In order to achieve the above object, the technical solution of the present invention is:

[0010] In a first aspect, a method for detecting chlorinated impurities in lurasidone hydrochloride raw materials comprises the following steps:

[0011] The lurasidone hydrochloride raw material is dissolved in formic acid and acetonitrile, diluted with water, precipitated by ultrasonication, and filtered to obtain a test solution; wherein the volume ratio of formic acid, acetonitrile and water is (0.9-1.1):(8-10):(85-95);

[0012] The test solution is tested by high performance liquid chromatography to obtain the content of chlorinated impurities in the lurasidone hydrochloride raw material;

[0013] Wherein, the structural formula of the chlorinated impurity is as follows:

[0014]

[0015] First, lurasidone hydrochloride is not easy to dissolve. Unlike the specific preparation test of lurasidone hydrochloride, the content of lurasidone hydrochloride in the lurasidone hydrochloride raw material is relatively high. Low solubility will lead to a lower content of lurasidone hydrochloride in the solution, which will lead to a lower content of other impurities such as chlorinated impurities in the lurasidone hydrochloride raw material, making it difficult to accurately detect the chlorinated impurities in the lurasidone hydrochloride raw material by chromatography. The present invention has found through research that acetonitrile aqueous solution can better dissolve lurasidone hydrochloride, thereby providing a detection basis for chromatography detection.

[0016] However, when the test sample and the reference sample were subjected to HPLC, it was found that the test sample of the present invention interfered with the detection of impurities. The reason for this is that both lurasidone hydrochloride and chlorinated impurities contain The structure of the chromatographic peaks is close to each other, and the content of lurasidone hydrochloride in the sample is too high, thereby interfering with the peak of chlorinated impurities. Therefore, the present invention first uses a solvent system of formic acid and acetonitrile to dissolve the lurasidone hydrochloride raw material, and then dilutes it with water to precipitate lurasidone hydrochloride, thereby reducing the content of the main component lurasidone hydrochloride in the sample, thereby reducing the influence of lurasidone hydrochloride on the peak of chlorinated impurities, thereby realizing the detection of chlorinated impurities in the lurasidone hydrochloride raw material.

[0017] In order to further reduce the impact of the test sample on the detection of impurities, in some embodiments, during the high performance liquid chromatography detection process, the chromatographic column uses phenylsilane bonded silica gel as a filler.

[0018] In order to further reduce the impact of the test sample on the detection of impurities and meet the baseline separation requirements for the detection of chlorinated impurities, in some embodiments, during the high performance liquid chromatography detection process, the mobile phase used is composed of mobile phase A and mobile phase B, wherein the mobile phase A is phosphate buffer and the mobile phase B is acetonitrile;

[0019] The elution method is gradient elution, and the conditions of the gradient elution are:

[0020]

[0021] In a second aspect, the present invention provides an application of the above detection method in quality control of lurasidone hydrochloride raw materials. The detection method can control the content of chlorinated impurities in lurasidone hydrochloride raw materials to be within 9.3 ppm.

[0022] The beneficial effects of the present invention are:

[0023] The detection method of the present invention effectively solves the gap in the current public standards for detecting the impurity, and can effectively detect the content of chlorinated impurities in the raw material of lurasidone hydrochloride. The detection method of the present invention has accurate and reliable results, is easy to operate, has high precision, good precision and linearity, and can effectively solve the problem that lurasidone hydrochloride is not easy to dissolve, and can dissolve up to 40 mg / ml. The detection method of the present invention solves the gap in the detection method of chlorinated impurities and can be used in the quality control of lurasidone hydrochloride raw material drug production. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] 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.

[0025] Figure 1 It is the positioning peak spectrum of the chlorinated impurity reference solution of Example 1 of the present invention.

[0026] Figure 2 It is the positioning peak spectrum of the test solution of Example 1 of the present invention.

[0027] Figure 3 This is the positioning peak spectrum of the chlorinated impurity reference solution of Example 2 of the present invention.

[0028] Figure 4 This is the positioning peak spectrum of the test solution of Example 2 of the present invention.

[0029] Figure 5 It is the positioning peak spectrum of the chlorinated impurity reference solution of Example 3 of the present invention.

[0030] Figure 6 This is the positioning peak spectrum of the test solution of Example 3 of the present invention.

[0031] Figure 7 It is a chromatogram of the chlorinated impurity reference solution, the test solution and the interfering solution of Example 4 of the present invention.

[0032] Figure 8 It is a linear curve diagram of the concentration-peak area of ​​the chlorinated impurities in Example 4 of the present invention.

[0033] Fig. 9It is the mixed solution spectrum of Example 4 of the present invention. DETAILED DESCRIPTION

[0034] It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0035] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0036] Since there is no method for detecting chlorinated impurities in lurasidone hydrochloride raw materials at present, which not only affects the quality control of lurasidone hydrochloride raw materials, but also affects the preparation of lurasidone hydrochloride raw materials in specific pharmaceutical preparations, the present invention proposes a method for detecting chlorinated impurities in lurasidone hydrochloride raw materials.

[0037] A typical embodiment of the present invention provides a method for detecting chlorinated impurities in lurasidone hydrochloride raw materials, comprising the following steps:

[0038] The lurasidone hydrochloride raw material is dissolved in formic acid and acetonitrile, diluted with water, precipitated by ultrasonication, and filtered to obtain a test solution; wherein the volume ratio of formic acid, acetonitrile and water is (0.9-1.1):(8-10):(85-95);

[0039] The test solution is tested by high performance liquid chromatography to obtain the content of chlorinated impurities in the lurasidone hydrochloride raw material;

[0040] Wherein, the structural formula of the chlorinated impurity is as follows:

[0041]

[0042] The present invention finds that the concentration of the test solution of lurasidone hydrochloride is relatively high (15 mg / mL), and the chlorinated impurities emerge after lurasidone hydrochloride. When the concentration of the test solution is relatively high, the detection of the chlorinated impurities is interfered. The present invention can effectively reduce the interference of the chlorinated impurities by making lurasidone hydrochloride dissolve first and then precipitate. The present invention adopts HPLC method for detection, which is simple to operate and low in cost.

[0043] The present invention does not impose any particular limitation on the preparation method of lurasidone hydrochloride, and any preparation method of raw materials commonly used in the art may be used.

[0044] In some embodiments, the ratio of the mass of lurasidone hydrochloride raw material to the total volume of formic acid, acetonitrile and water is 150 mg: (8-12) mL.

[0045] In some embodiments, the ultrasound time is 20 to 40 min, more preferably 25 to 35 min, and most preferably 30 min.

[0046] In some embodiments, during the high performance liquid chromatography detection process, the chromatographic column uses phenylsilane bonded silica gel as a filler. Specifically, the model of the chromatographic column is XB-Phenyl 4.6×250mm, 5μm; or a chromatographic column with equivalent performance.

[0047] In some embodiments, during the high performance liquid chromatography detection process, the mobile phase used is composed of mobile phase A and mobile phase B, wherein the mobile phase A is phosphate buffer and the mobile phase B is acetonitrile;

[0048] The elution method is gradient elution, and the conditions of the gradient elution are:

[0049]

[0050] Specifically, the phosphate buffer is a phosphate buffer containing triethylamine. More specifically, the phosphate buffer is a potassium dihydrogen phosphate solution, and the concentration of potassium dihydrogen phosphate is 0.013-0.017 mol / L. More specifically, the pH of the phosphate buffer is 5.9-6.1.

[0051] Specifically, the conditions of the gradient elution are:

[0052]

[0053] In some embodiments, during HPLC detection, the flow rate of the mobile phase is 0.9-1.1 mL / min, more preferably 1.0 mL / min.

[0054] In some embodiments, during HPLC detection, the column temperature is 25-35°C, more preferably 30°C.

[0055] In some embodiments, during HPLC detection, the detection wavelength is 225-235 nm, more preferably 230 nm.

[0056] In some embodiments, during HPLC detection, the injection volume is 15 to 25 μL, more preferably 20 μL.

[0057] In the present invention, the method for determining the content of chlorinated impurities in the lurasidone hydrochloride raw material is specifically as follows: taking a reference solution of chlorinated impurities, determining it by the HPLC method, obtaining a chromatogram, and calculating the content of chlorinated impurities in the test solution by the peak area using the external standard method.

[0058] In the present invention, the preparation method of the reference solution of the chlorinated impurity is as follows: take an appropriate amount of the chlorinated impurity, accurately weigh it, add acetonitrile to dissolve and dilute it to make a solution containing about 1.4 μg per 1 ml, accurately measure 1 ml, put it in a 10 ml volumetric flask, dilute it to the scale with formic acid-acetonitrile-water (1:9:90), shake well, and obtain it.

[0059] The present invention also provides an application of the above detection method in the quality control of lurasidone hydrochloride raw materials to avoid adverse effects of chlorinated impurities on the human body. According to the guidelines for the control of genotoxic impurities, the limit is 1.5 μg / day, and the maximum dosage of lurasidone hydrochloride (160 mg / day), so the limit of chlorination is set at 9.3 ppm.

[0060] 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.

[0061] Embodiment 1:

[0062] Preparation of test solution: Take about 150 mg of the product, weigh accurately, place in a 10 mL volumetric flask, add solvent to dissolve, shake well, and obtain.

[0063] Reference solution: Take about 1 mg of chlorinated impurity, weigh accurately, place in a 10 mL volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0064] Chromatographic conditions:

[0065] Chromatographic column: octadecylsilane bonded silica gel as filler (XB-C18, 4.6 mm × 250 mm, 5 μm);

[0066] UV detector (detection wavelength: 230nm);

[0067] Mobile phase A: 0.015 mol / L potassium dihydrogen phosphate solution (pH adjusted to 6.0 with triethylamine);

[0068] Mobile phase B: acetonitrile;

[0069] Injection volume: 20 μL;

[0070] Column temperature: 30°C;

[0071] Flow rate: 1.0 mL / min;

[0072] Solvent: acetonitrile-water (80:20).

[0073] Perform gradient elution according to the following table:

[0074] Time (min) A% (volume fraction) B% (volume fraction) 0 60 40 10 60 40 40 20 80 75 20 80 75.1 60 40 90 60 40

[0075] from Figure 1 and Figure 2 It can be seen that the test sample interferes with the detection of impurities, and adjustment of gradient elution should be considered for method optimization.

[0076] Embodiment 2:

[0077] The preparation of the test solution and the reference solution is the same as in Example 1.

[0078] Chromatographic column: octadecylsilane bonded silica gel as filler (XB-C18, 4.6 mm × 250 mm, 5 μm);

[0079] UV detector (detection wavelength: 230nm);

[0080] Mobile phase A: 0.015 mol / L potassium dihydrogen phosphate solution (pH adjusted to 6.0 with triethylamine);

[0081] Mobile phase B: acetonitrile;

[0082] Injection volume: 20 μL;

[0083] Column temperature: 30°C;

[0084] Flow rate: 1.0 mL / min;

[0085] Solvent: acetonitrile-water (80:20).

[0086] Perform gradient elution according to the following table:

[0087]

[0088]

[0089] from Figure 3 and Figure 4 It can be seen that the test sample interferes with the detection of impurities. Considering that lurasidone hydrochloride and the known impurities (impurities in each standard) both contain benzene rings, the chromatographic column was replaced with a phenyl column for gradient method optimization.

[0090] Embodiment 3:

[0091] In order to reduce the interference of the main component, it is dissolved first and then precipitated.

[0092] Test solution: Take about 150 mg of lurasidone hydrochloride raw material, weigh accurately, place in a 10 mL volumetric flask, add 1 mL of formic acid-acetonitrile (1:9) solution, heat to dissolve, dilute to the scale with water, shake well, ultrasonicate to precipitate, filter, and take the filtrate to obtain; the concentration of lurasidone hydrochloride is recorded as 15 mg / ml.

[0093] Reference substance solution: Take about 10 mg of chlorinated impurities, weigh accurately, place in a 100 mL volumetric flask, add acetonitrile to dissolve and dilute to scale, shake well, and use as reference substance stock solution ①. Accurately measure 1.4 mL of reference substance stock solution ①, place in a 100 mL volumetric flask, dilute to scale with acetonitrile, shake well, and use as reference substance stock solution ②. Accurately measure 1 mL of reference substance stock solution ②, place in a 10 mL volumetric flask, dilute to scale with solvent, shake well, and obtain; the concentration of chlorinated impurities is 0.14 μg / mL.

[0094] Chromatographic column: XB-Phenyl (4.6×250 mm, 5 μm);

[0095] Mobile phase A: 0.015 mol / L potassium dihydrogen phosphate solution, pH adjusted to 6.0 with triethylamine;

[0096] Mobile phase B: acetonitrile;

[0097] Column temperature: 30°C;

[0098] Flow rate: 1.0 mL / min;

[0099] Detection wavelength: 230nm;

[0100] Injection volume: 20 μL;

[0101] Solvent: formic acid-acetonitrile-water (1:9:90).

[0102] Gradient table:

[0103] Time (min) A% (volume fraction) B% (volume fraction) 0 80 20 60 20 80 80 20 80 85 80 20 100 80 20

[0104] from Figure 5 and Figure 6 It can be seen that the chlorinated impurities peaked after the main component, but did not achieve baseline separation. The organic phase ratio was reduced for optimization.

[0105] Embodiment 4:

[0106] The preparation of the test solution and the reference solution is the same as in Example 3.

[0107] Chromatographic column: XB-Phenyl (4.6×250 mm, 5 μm);

[0108] Mobile phase A: 0.015 mol / L potassium dihydrogen phosphate solution, pH adjusted to 6.0 with triethylamine;

[0109] Mobile phase B: acetonitrile;

[0110] Column temperature: 30°C;

[0111] Flow rate: 1.0 mL / min;

[0112] Detection wavelength: 230nm;

[0113] Injection volume: 20 μL;

[0114] Solvent: formic acid-acetonitrile-water (1:9:90).

[0115] Gradient table:

[0116]

[0117]

[0118] Depend on Figure 7 It can be seen that reducing the proportion of organic phase and delaying the chlorination peak can effectively separate chlorinated impurities from the main component, and interfering impurities do not interfere with the detection of chlorinated impurities.

[0119] The mixed solution of lurasidone hydrochloride and chlorinated impurities was injected, and lurasidone hydrochloride and chlorinated impurities were well separated. Fig. 9 shown.

[0120] The method of Example 4 was validated by methodology, and the validation targets included the limit of quantification and detection, specificity and system suitability, linearity, and precision. The specific methods included:

[0121] 1. Specificity experiment

[0122] Reference substance solution: Take about 10 mg of chlorinated impurities, weigh accurately, place in a 100 mL volumetric flask, add acetonitrile to dissolve and dilute to scale, shake well, and use as reference substance stock solution ①. Accurately measure 1.4 mL of reference substance stock solution ①, place in a 100 mL volumetric flask, dilute to scale with acetonitrile, shake well, and use as reference substance stock solution ②. Accurately measure 1 mL of reference substance stock solution ②, place in a 10 mL volumetric flask, dilute to scale with solvent, shake well, and obtain; the concentration of chlorinated impurities in the reference substance solution is 0.14 μg / mL.

[0123] Test solution: Take about 150 mg of lurasidone hydrochloride raw material, weigh accurately, place in a 10 mL volumetric flask, add 1 mL of formic acid-acetonitrile (1:9) solution, heat to dissolve, dilute to the scale with water, shake well, precipitate by ultrasound, filter, and take the filtrate to obtain; the concentration of lurasidone hydrochloride in the test solution is recorded as 15 mg / mL.

[0124] Interference solution: Take about 1 mg of each of impurities 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20, accurately weigh, place in the same 10 mL volumetric flask, add acetonitrile to dissolve and dilute to scale, shake well, as the impurity mixed solution. Accurately measure 1.5 mL of the impurity mixed solution, place in a 10 mL volumetric flask, dilute to scale with solvent, shake well, and obtain; the concentration of impurities in the interference solution is 15 μg / mL.

[0125] Mixed solution: Take about 150 mg of lurasidone hydrochloride raw material, weigh it accurately, put it in a 10 mL volumetric flask, add 1 mL of formic acid-acetonitrile (1:9) solution, heat to dissolve, add appropriate amount of water, shake well, sonicate to precipitate, accurately measure into 1 ml of reference substance stock solution ②, dilute to the scale with water, shake well, filter, and take the filtrate to obtain; in the mixed solution, the concentration of chlorinated impurities is 0.14 μg / mL, and the concentration of the test sample is recorded as 15 mg / mL.

[0126] Table 1 Specificity experiments and results

[0127]

[0128] 2. System suitability

[0129] System suitability solution: Accurately measure the reference solution under the specific test item as the system suitability solution.

[0130] Accurately measure 20 μL of the system suitability solution, inject it into the liquid chromatograph, and record the chromatogram. The test results are shown in Table 2 below.

[0131] Table 2 System suitability experiments and results

[0132] name Element Retention time Peak area Theoretical plate number System Suitability Solution 1 Chlorinated impurities 64.385 118005 198727 System Suitability Solution 2 Chlorinated impurities 64.398 111704 211828 System Suitability Solution 3 Chlorinated impurities 64.443 115114 192233 System Suitability Solution 4 Chlorinated impurities 64.205 115936 92787 System Suitability Solution 5 Chlorinated impurities 64.333 107639 174323 average - 64.353 113680 - RSD% - 0.15 3.58 -

[0133] 3. Limit of Quantitation and Limit of Detection

[0134] Quantitative limit solution: Take the reference solution under the specificity item and continuously dilute it to make S / N≈10.

[0135] Detection limit solution: Accurately measure 3 mL of the quantitation limit solution, place it in a 10 mL volumetric flask, dilute to the scale with solvent, and shake well.

[0136] Accurately measure 20 μL of each of the above solutions, inject into the liquid chromatograph, and record the chromatogram. The test results are shown in Table 3 below.

[0137] Table 3 Quantitation limit and detection limit experiments and results

[0138]

[0139]

[0140] 4. Linear

[0141] Linear stock solution: Take reference stock solution ② under the specificity item as the linear stock solution.

[0142] Accurately measure 1mL, 1.6mL, 2mL, 3mL, and 4mL of the linear stock solution and place them in different 20mL volumetric flasks. Dilute to the scale with solvent and shake well to prepare a linear concentration series solution with approximately 0.07μg (50%), 0.112μg (80%), 0.14μg (100%), 0.21μg (150%), and 0.28μg (200%) of chlorinated impurities per 1mL.

[0143] Accurately measure 20 μL of the quantitative limit solution and the above linear solution, inject them into the liquid chromatograph, record the chromatogram, and perform linear regression on the peak area with concentration. The test results are shown in Table 4 and Figure 8 shown.

[0144] Table 4 Linearity test and results

[0145]

[0146]

[0147] 5. Precision

[0148] Precision solution: Take about 150 mg of lurasidone hydrochloride raw material, weigh accurately, place in a 10 mL volumetric flask, add 1 mL of formic acid-acetonitrile (1:9) solution, heat to dissolve, dilute to scale with water, shake well, ultrasonicate to precipitate, filter, and take the filtrate. Prepare 6 portions in the same way.

[0149] Accurately measure 20 μL of the precision solution, inject it into the liquid chromatograph, and record the chromatogram. The test results are shown in Table 5 below:

[0150] Table 5 Precision test and results

[0151]

[0152] The results of the methodological validation are summarized in Table 6 below.

[0153] Table 6 Summary of method validation results

[0154]

[0155]

[0156] The lurasidone hydrochloride chlorinated impurity test project has been validated by methodology. No deviation or change occurred during the test, and the test results all met the established standard requirements. Based on existing knowledge and data, it is proved that the test method meets the inspection requirements and is suitable for quality control testing of lurasidone hydrochloride raw materials.

[0157] 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 method for detecting chlorinated impurities in lurasidone hydrochloride raw materials, characterized in that: The steps include: The lurasidone hydrochloride raw material is dissolved in formic acid and acetonitrile, diluted with water, precipitated by ultrasonication, and filtered to obtain a test solution; wherein the volume ratio of formic acid, acetonitrile and water is (0.9-1.1):(8-10):(85-95); The test solution is tested by high performance liquid chromatography to obtain the content of chlorinated impurities in the lurasidone hydrochloride raw material; Wherein, the structural formula of the chlorinated impurity is as follows:

2. The detection method according to claim 1, characterized in that: The mass ratio of lurasidone hydrochloride raw material to the total volume of formic acid, acetonitrile and water is 150 mg: (8-12) mL.

3. The detection method according to claim 1, characterized in that: The ultrasonic time is 20 to 40 minutes, more preferably 25 to 35 minutes, and most preferably 30 minutes.

4. The detection method according to claim 1, characterized in that: During the high performance liquid chromatography detection process, the chromatographic column uses phenylsilane bonded silica gel as a filler; preferably, the model of the chromatographic column is XB-Phenyl 4.6×250 mm, 5 μm.

5. The detection method according to claim 1, characterized in that: During the high performance liquid chromatography detection process, the mobile phase used consists of mobile phase A and mobile phase B, wherein the mobile phase A is phosphate buffer and the mobile phase B is acetonitrile; The elution method is gradient elution, and the conditions of the gradient elution are:

6. The detection method according to claim 5, characterized in that: The phosphate buffer is a phosphate buffer containing triethylamine; preferably, the phosphate buffer is a potassium dihydrogen phosphate solution, and the concentration of potassium dihydrogen phosphate is 0.013-0.017 mol / L; preferably, the pH of the phosphate buffer is 5.9-6.

1.

7. The detection method according to claim 5, characterized in that: The conditions of the gradient elution are:

8. The detection method according to claim 1, characterized in that: During the HPLC detection process, the flow rate of the mobile phase is 0.9 to 1.1 mL / min, more preferably 1.0 mL / min; Alternatively, during high performance liquid chromatography detection, the injection volume is 15 to 25 μL, more preferably 20 μL.

9. The detection method according to claim 1, characterized in that: During the HPLC detection process, the column temperature is 25 to 35°C, more preferably 30°C; Alternatively, during high performance liquid chromatography detection, the detection wavelength is 225 to 235 nm, more preferably 230 nm.

10. Use of the detection method according to any one of claims 1 to 9 in quality control of lurasidone hydrochloride raw materials.

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