HPLC (High Performance Liquid Chromatography) detection method of ipragmine hydrochloride enantiomer

Abstract

The invention discloses an HPLC (High Performance Liquid Chromatography) detection method for ipragmine hydrochloride enantiomers, and belongs to the technical field of pharmaceutical analysis. The HPLC detection method provided by the invention comprises the following steps: dissolving ipragmine hydrochloride to be detected in a diluent to prepare a test solution; detecting the test solution by adopting normal-phase high performance liquid chromatography; the stationary phase of the normal-phase high performance liquid chromatography is silica gel of which the surface is covalently bonded with cellulose-tri (3-chloro-4-methyl phenyl carbamate); a mobile phase of the normal-phase high performance liquid chromatography is a mixed solution of normal hexane, isopropanol, trifluoroacetic acid and diethylamine. According to the detection method established by the invention, the ipragmine hydrochloride main peak and the S-configuration enantiomer impurity peak can be subjected to baseline separation, the separation degree can reach 4.5 or above, the method is high in specificity and sensitivity, and various methodology verification parameters all meet the drug quality control requirements.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical analysis technology, and in particular to an HPLC method for the detection of enantiomers of iglimepiride hydrochloride. Background Technology

[0002] The information disclosed in the background section of this invention is intended only to enhance the understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Chiral drugs often generate enantiomeric impurities during synthesis. Although these impurities have similar chemical structures, their pharmacological activities, metabolic kinetics, and toxicological properties may differ significantly, directly affecting the safety and efficacy of the drug. Therefore, establishing specific, accurate, and reliable methods for controlling enantiomeric impurities is crucial for the quality research and control of chiral drugs.

[0004] Igglitazone hydrochloride is an antidiabetic drug containing a chiral center. Studies have shown that its R-enantiomer has higher glycemic regulatory activity and lower toxicity, while the S-enantiomer has weaker efficacy and may affect drug safety. Therefore, strictly controlling the content of specific enantiomer impurities in the drug is a key quality attribute to ensure its clinical efficacy and medication safety. Currently, the separation and analysis of enantiomers of chiral compounds often employs chiral stationary phase high-performance liquid chromatography (HPLC), chiral derivatization, or chiral mobile phase additive methods. However, these common strategies face many challenges in practical applications. For example, while liquid chromatography-tandem mass spectrometry (LC-MS / MS) techniques offer high sensitivity, they rely on expensive large-scale instruments, and the method development and operation procedures are complex, resulting in high analytical costs and making it difficult to widely promote in routine quality control. In addition, some traditional chiral chromatographic columns, such as protein columns or physically coated stationary phases, suffer from insufficient chemical stability and solvent tolerance, leading to rapid column efficiency decline and short lifespan during use. They may also have special requirements for storage conditions, affecting the robustness and economy of the analytical method. Especially for the specific compound igglimepiride, there is a lack of dedicated analytical methods in the current technology that can balance efficient separation, good robustness and ease of operation.

[0005] Therefore, there is an urgent need in this field to develop a method for detecting enantiomers of iggliformin hydrochloride that is specific, sensitive, has stable column performance, and is easy to implement in an industrial quality control environment, in order to fill this technological gap. Summary of the Invention

[0006] In view of this, the present invention provides an HPLC detection method for enantiomers of iglimepiride hydrochloride. The present invention uses a specific chiral stationary phase and mobile phase system to achieve efficient separation and accurate determination of enantiomers of iglimepiride hydrochloride.

[0007] In a first aspect, the present invention provides an HPLC method for the detection of enantiomers of iglimepiride hydrochloride, comprising the following steps: Prepare a test solution by dissolving the ioglitazone hydrochloride to be tested in a diluent; The test solution was detected by normal-phase high-performance liquid chromatography; The stationary phase of the normal-phase high-performance liquid chromatography is silica gel with cellulose-tris(3-chloro-4-methylphenylcarbamate) covalently bonded to its surface; The mobile phase of the normal-phase high-performance liquid chromatography is a mixture of n-hexane, isopropanol, trifluoroacetic acid, and diethylamine.

[0008] Preferably, the diluent is ethanol.

[0009] Preferably, the concentration of the test solution is 0.4~1 mg / mL.

[0010] Preferably, the volume ratio of hexane, isopropanol, trifluoroacetic acid, and diethylamine is (78~82): (18~22): (0.08~0.12): (0.015~0.025).

[0011] Furthermore, the volume ratio of hexane, isopropanol, trifluoroacetic acid, and diethylamine is 80:20:0.1:0.02.

[0012] Preferably, the stationary phase of the normal-phase high-performance liquid chromatography is a CHIRALPAK IM column.

[0013] Furthermore, the CHIRALPAK IM chromatographic column has a length of 150 mm and an inner diameter of 4.6 mm; the stationary phase has a particle size of 5 μm.

[0014] Preferably, the column temperature of the normal-phase high-performance liquid chromatography is 30~40℃; the detection wavelength is 230~245nm; the flow rate is 0.8~1.2mL / min; and the injection volume is 0.3~0.6μL.

[0015] Preferably, the column temperature of the normal-phase high-performance liquid chromatography is 33~37℃; the detection wavelength is 240nm.

[0016] Secondly, the present invention provides the application of the above-mentioned HPLC detection method for enantiomers of iglimepiride hydrochloride in the quality control of iglimepiride hydrochloride pharmaceutical preparations.

[0017] Compared with the prior art, the present invention has achieved the following beneficial effects: (1) The HPLC detection method for enantiomers of iglimepiride hydrochloride established in this invention uses silica gel with cellulose-tris(3-chloro-4-methylphenylcarbamate) covalently bonded to its surface as the stationary phase and a mixed solution of n-hexane-isopropanol-trifluoroacetic acid-diethylamine as the mobile phase. This method successfully achieves efficient separation of enantiomers from the main component, with a resolution of 4.5 or higher, which is significantly better than the separation effect of conventional chiral columns, ensuring the accuracy and specificity of the detection results.

[0018] (2) This method uses a solvent-resistant chiral column, which has excellent chemical stability and solvent tolerance compared with traditional protein columns or coated stationary phases. The column efficiency decreases slowly and the service life is significantly extended. It effectively overcomes the defects of poor column durability and harsh storage conditions in the existing technology. At the same time, it shortens the single analysis run time to 25 minutes and greatly improves the detection efficiency.

[0019] (3) The above method of the present invention is based on a conventional high performance liquid chromatography platform, avoiding reliance on expensive and complex liquid chromatography-tandem mass spectrometry instruments. The operation process is simple, the sample does not require complex pretreatment, and the use of ethanol as a diluent is low-cost and environmentally friendly. All validation parameters meet the requirements of drug quality control, providing a reliable, economical and easy-to-promote standardized analytical method for the quality control of ioglitamin hydrochloride raw materials and preparations. Attached Figure Description

[0020] The accompanying drawings, which form part of this specification, are used to provide a further understanding of the invention. The illustrative embodiments and descriptions of the invention are used to explain the invention and do not constitute an undue limitation thereof. Obviously, those skilled in the art can obtain other drawings based on these drawings without any inventive effort.

[0021] Figure 1 This is a liquid chromatogram of the reference solution of Example 1 of the present invention; Figure 2 This is a liquid chromatogram of the test solution of Example 1 of the present invention; Figure 3 This is a linear graph of the concentration and peak area of ​​ipagrimidine hydrochloride reference standard in Example 1 of the present invention; Figure 4 This is a chromatogram of the test solution of Comparative Example 1 of the present invention. Detailed Implementation

[0022] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0023] As described in the background section, the molecular structure of iglimepiride hydrochloride contains a chiral center, which may produce two enantiomers, R-configuration and S-configuration, during synthesis.

[0024] The structural formula for the S-configuration is as follows: .

[0025] The structural formula for the R-configuration is as follows: .

[0026] Studies have shown that the R-enantiomer has higher glycemic regulatory activity and lower toxicity, while the S-enantiomer has weaker efficacy and may affect drug safety. Therefore, it is crucial to establish analytical methods that can effectively separate and accurately quantify these two enantiomers.

[0027] Therefore, the present invention provides an HPLC detection method for enantiomers of igliamine hydrochloride, comprising the following steps: Prepare a test solution by dissolving the ioglitazone hydrochloride to be tested in a diluent; The test solution was detected by normal-phase high-performance liquid chromatography; The stationary phase of the normal-phase high-performance liquid chromatography is silica gel with cellulose-tris(3-chloro-4-methylphenylcarbamate) covalently bonded to its surface; The mobile phase of the normal-phase high-performance liquid chromatography is a mixture of n-hexane, isopropanol, trifluoroacetic acid, and diethylamine.

[0028] In this invention, the test solution is first prepared by dissolving the ipagliptin hydrochloride to be tested in a suitable diluent. The diluent is preferably ethanol, which has good compatibility with the normal-phase chromatographic mobile phase, ensuring sufficient sample dissolution while avoiding peak distortion or bifurcation due to solvent effects. The concentration of the test solution is preferably controlled in the range of 0.4–1 mg / mL, more preferably 0.5 mg / mL. This concentration range ensures detection sensitivity while avoiding column overload, ensuring the symmetry of peak shapes and quantitative accuracy of the R-configuration and S-configuration enantiomers.

[0029] The prepared test solution is injected into a high-performance liquid chromatograph (HPLC) for normal-phase chromatographic analysis. The stationary phase of the normal-phase HPLC described in this invention is silica gel with cellulose-tris(3-chloro-4-methylphenylcarbamate) covalently bonded to its surface. Its chiral recognition mechanism is mainly based on multiple intermolecular forces formed between the stationary phase and enantiomer molecules, including hydrogen bonding, π-π stacking interactions, and dipole-dipole interactions, thereby achieving chiral recognition and separation of enantiomers. The preferred stationary phase is a CHIRALPAK IM column, which is a covalently bonded chiral stationary phase. Compared with traditional coated or protein-based chiral columns, it has excellent solvent resistance and chemical stability, can withstand a variety of organic solvents, has a significantly extended column life, and requires no special storage conditions.

[0030] In this invention, the preferred size of the CHIRALPAK IM chromatographic column is 150 mm × 4.6 mm, and the stationary phase particle size is 5 μm. This specification achieves the best balance between separation efficiency, analysis time, and column pressure.

[0031] In this invention, the mobile phase of normal-phase high-performance liquid chromatography (HPLC) is a mixed solution of n-hexane, isopropanol, trifluoroacetic acid, and diethylamine. Hexane serves as the nonpolar host of the mobile phase, while isopropanol acts as a polar regulator; by altering their ratio, the retention time and separation selectivity of the sample can be controlled. Trifluoroacetic acid and diethylamine, as mobile phase additives, constitute an acid-base pair adjustment system, effectively suppressing secondary interactions of silanol groups, significantly improving peak shape, reducing tailing, and enhancing resolution and detection sensitivity. The preferred volume ratio of each component is (78~82):(18~22):(0.08~0.12):(0.015~0.025), more preferably 80:20:0.1:0.02. Within this range, baseline separation of enantiomers and symmetrical peak shapes are ensured; deviations from this range may lead to a significant decrease in resolution or deterioration of peak shape.

[0032] In the chromatographic analysis conditions of this invention, column temperature has a significant impact on separation selectivity and analytical reproducibility. This invention controls the column temperature within the range of 30–40°C, more preferably 33–37°C, and even more preferably 35°C. This temperature condition is beneficial for maintaining the conformational stability of the chiral stationary phase, while simultaneously promoting chiral recognition between enantiomers and the stationary phase, ensuring separation reproducibility. The detection wavelength is preferably 230–245 nm, more preferably 240 nm. Within this wavelength range, iriglimine hydrochloride and its enantiomers exhibit strong ultraviolet absorption, meeting the sensitivity requirements for trace impurity detection. The mobile phase flow rate is preferably 0.8–1.2 mL / min, more preferably 1.0 mL / min; the injection volume is preferably 0.3–0.6 μL, more preferably 0.5 μL. These parameters together constitute a highly efficient and stable analytical system, capable of completing a full analysis within 25 minutes, significantly improving detection efficiency.

[0033] The detection method established in this invention enables baseline separation between the main peak of ipagliptin hydrochloride and its S-configuration enantiomer impurity peak, achieving a resolution of over 4.5, far exceeding the 1.5 baseline separation standard specified in the pharmacopoeia. This method exhibits high specificity and sensitivity, with a limit of quantitation of 0.1%, a limit of detection of 0.05%, a linear range covering 0.1%–10%, and an accuracy between 98% and 102%. All methodological validation parameters meet the requirements for drug quality control.

[0034] This invention also provides the application of the above-mentioned HPLC detection method for enantiomers of ipagliptin hydrochloride in the quality control of ipagliptin hydrochloride pharmaceutical preparations. This method is based on a conventional high-performance liquid chromatography platform, requires no complex sample pretreatment or expensive mass spectrometry detectors, is simple to operate, provides rapid analysis, and is low in cost. It can effectively monitor the content of R-configuration and S-configuration enantiomers in active pharmaceutical ingredients and preparations, providing a reliable, economical, and easily scalable standardized analytical method for the quality control of ipagliptin hydrochloride active pharmaceutical ingredients and preparations, and has good prospects for industrial application.

[0035] The technical solution of the present invention will be further described below with reference to specific embodiments. The present invention does not impose any special restrictions on the source of reagents used in the following embodiments; commercially available products well known to those skilled in the art can be used.

[0036] In the following examples, the iglimepiride hydrochloride raw material and the enantiomer reference standard (S-configuration accounted for 74.8%) were both prepared in-house.

[0037] Example 1 This embodiment provides an HPLC method for the detection of enantiomers of iglimepiride hydrochloride.

[0038] 1. Solution preparation Test solution: Accurately weigh 10 mg of ioglitazone hydrochloride raw material, place it in a 20 mL volumetric flask, dissolve and dilute to the mark with ethanol, shake well, and prepare a test solution with a concentration of 0.5 mg / mL.

[0039] Reference solution: Accurately weigh 20 mg of enantiomer reference standard, place it in a 20 mL volumetric flask, dissolve and dilute to the mark with ethanol, shake well, measure 1 mL of the above solution into a 50 mL volumetric flask, dilute to the mark with ethanol, shake well, and prepare a reference solution with a concentration of 0.02 mg / mL.

[0040] 2. Chromatographic conditions Column: CHIRALPAK IM (150 mm × 4.6 mm, 5 μm); Mobile phase: n-hexane-isopropanol-trifluoroacetic acid-diethylamine (volume ratio 80:20:0.1:0.02); Flow rate: 1.0 mL / min; Column temperature: 35℃; Detection wavelength: 240 nm; Injection volume: 5 μL; Running time: 25 min.

[0041] 3. System suitability test Inject the test solution and the reference solution separately and record the chromatograms. The liquid chromatogram of the reference solution is shown below. Figure 1 As shown, in the reference solution, the S-configuration enantiomer (retention time 8.245 min) accounted for 74.8%, and the R-configuration enantiomer (retention time 12.179 min) accounted for 25.2%. The liquid chromatogram of the test solution is shown below. Figure 2 As shown, the retention time of the main peak of iglimepiride hydrochloride was 12.064 min, the retention time of the S-configuration enantiomer impurity peak was 8.371 min, the resolution reached 4.5, the theoretical plate number was higher than 5000, and the tailing factor was less than 1.2, indicating that the system has good applicability.

[0042] 4. Methodological Validation (1) Specificity: Blank solvent (ethanol), test solution and S-configuration impurity reference solution were injected separately. The results showed that the blank solvent did not interfere with the target peak position; the R-configuration principal component peak and the S-configuration impurity peak in the test solution could both achieve baseline separation, indicating that the method has good specificity.

[0043] (2) Repeatability and intermediate precision: Repeatability test: The same test solution was precisely measured and injected 6 times consecutively under the above chromatographic conditions. The relative standard deviation (RSD) of the peak area of ​​the S-configuration enantiomer was calculated. The results are shown in Table 1.

[0044] Intermediate precision test: To examine the reproducibility of the analytical method under different test conditions, intermediate precision verification was performed. On different dates, another high performance liquid chromatograph of the same model and a new chromatographic column of the same brand were used to perform the test according to the same sample preparation method and chromatographic conditions. A total of 6 sets of valid data were obtained, and the results are shown in Table 1.

[0045] Table 1 Repeatability and intermediate precision data

[0046] As shown in Table 1, the RSD of the S-configuration enantiomer content after 6 injections in the repeatability test was 4.2%, indicating that the method has good precision under the same operating conditions. The intermediate precision RSD was 4.5%, indicating that the method has good reproducibility among different analysts, different instruments, and different dates, and can meet the requirements of routine quality control.

[0047] (3) Linear range: Accurately weigh iodine hydrochloride reference standard, dilute with ethanol to prepare a series of solutions of known concentrations, and inject them sequentially for analysis. Perform linear regression on peak area (X) against concentration (Y, mg / mL). The results are shown in Table 2 and... Figure 3 As shown.

[0048] Table 2 Linear Data

[0049] From Table 2 and Figure 3 As can be seen, the S-configuration enantiomer exhibits good linearity in the range of 0.002–1.014 mg / mL, with a regression equation of y = 0.0015x - 0.0026 and R0. 2 = 0.9996.

[0050] (4) Sensitivity: The quantitation limit data and detection limit data are shown in Table 3 and Table 4, respectively.

[0051] Table 3 Limits of Quantification Data

[0052] Table 4 Detection Limit Data

[0053] As can be seen from Tables 3 and 4, the limit of quantitation (signal-to-noise ratio ≥10) is 0.002 mg / mL and the limit of detection (signal-to-noise ratio ≥3) is 0.001 mg / mL, indicating high detection sensitivity.

[0054] (5) Accuracy: In the test sample with a known background content of S-configuration impurities, the above-mentioned reference solution was precisely added to achieve levels equivalent to 50%, 100%, and 150% of the theoretical content of S-configuration impurities, respectively. Three replicates were prepared for each level, and the determination was performed according to the above method. The recovery rate was calculated based on the actual amount of S-configuration impurities added, and the results are shown in Table 5.

[0055] Table 5 Accuracy Data

[0056] As can be seen from Table 5, the recovery rate of the samples was between 88% and 103%, which met the quality control requirements.

[0057] (6) Durability: The test results after changing the flow rate are shown in Table 6.

[0058] Table 6 Durability Test Results - Variation in Flow Rate

[0059] The test results after changing the column temperature are shown in Table 7.

[0060] Table 7 Durability Test Results - Variation in Flow Rate

[0061] The test results after changing the chromatographic column are shown in Table 8.

[0062] Table 8. Durability Test Results - Replacement of Chromatographic Column

[0063] Tables 6, 7, and 8 show that under the original conditions, with a flow rate of ±0.2 ml and a column temperature of ±2 ℃, and by replacing the same type of chromatographic column with the same conditions, the changes in retention time (relative deviation) of each peak in the chromatogram of the system suitability solution under the changed conditions did not exceed 15%, and the relative deviation of peak area did not exceed 10%, indicating that the method has good robustness.

[0064] This embodiment successfully established an HPLC method specifically for the separation and quantification of the R-configuration of ipagliptin hydrochloride active pharmaceutical ingredient and its S-configuration enantiomer impurities. This method employs a solvent-resistant chiral stationary phase column and an optimized normal-phase mobile phase system, achieving chiral recognition through molecular interactions such as hydrogen bonding and π-π stacking between the enantiomers and the stationary phase. The synergistic effect of trifluoroacetic acid and diethylamine in the mobile phase effectively suppresses the silanol effect, improves peak shape, and enhances separation efficiency. This method is highly specific and sensitive, suitable for the quality control of ipagliptin hydrochloride active pharmaceutical ingredient, and can effectively ensure the safety and efficacy of clinical medication.

[0065] Comparative Example 1 This comparative example used a reversed-phase chromatography system and a protein column. The specific detection method for this comparative example is as follows: 1. Solution preparation Test solution: Accurately weigh 10 mg of ipagrimidine hydrochloride raw material, place it in a 25 mL volumetric flask, dissolve and dilute with purified water to the mark, and shake well to prepare a test solution with a concentration of 0.4 mg / mL.

[0066] Reference solution: Accurately weigh 10 mg of enantiomer reference standard, place it in a 20 mL volumetric flask, dissolve and dilute to the mark with purified water, take 1 mL of the above solution, place it in a 25 mL volumetric flask, dilute to the mark with purified water, and shake well to obtain a reference solution with a concentration of 0.02 mg / mL.

[0067] 2. Chromatographic conditions Column: CHIRRALPAK CBH (150 mm × 4.0 mm, 5 μm); Mobile phase: 20 mM ammonium acetate aqueous solution; Flow rate: 0.3 mL / min; Column temperature: 15℃; Detection wavelength: 220 nm; Injection volume: 5 μL; Running time: 60 min.

[0068] The chromatogram of the test solution in this embodiment is as follows: Figure 4 As shown, the results are summarized in Table 9.

[0069] Table 9 Chromatographic data of the test solution of Comparative Example 1

[0070] While this method can achieve a resolution of 1.58, the analysis run time is as long as 60 minutes, resulting in low efficiency. More importantly, the protein columns used have extremely poor durability, with peak shapes deteriorating significantly after 3-5 uses. Furthermore, they are expensive and require storage at 2-8°C, greatly limiting their application in industrial quality control.

[0071] Comparative Example 2 The difference between this comparative example and Example 1 is that the chromatographic column used in this comparative example is CHIRALPAK AD-H (250 mm × 4.6 mm, 5 μm), and the mobile phase is n-hexane-anhydrous ethanol-trifluoroacetic acid-diethylamine (volume ratio 70:30:0.1:0.1).

[0072] The resolution was found to be 0.8, indicating that the S-configuration and R-configuration enantiomers could not be separated normally.

[0073] Comparative Example 3 The difference between this comparative example and Example 1 is that the chromatographic column used in this comparative example is CHIRALPAK AD-H (250 mm × 4.6 mm, 5 μm), and the mobile phase is n-hexane-anhydrous ethanol-trifluoroacetic acid-diethylamine (volume ratio 90:10:0.1:0.05).

[0074] The resolution was found to be 0.4, indicating that the S-configuration and R-configuration enantiomers could not be separated normally.

[0075] Comparative Example 4 The difference between this comparative example and comparative example 1 is that the chromatographic column of this comparative example is CHIRALPAK AY-H (250 mm × 4.6 mm, 5 μm).

[0076] The resolution was found to be 0.5, indicating that the S-configuration and R-configuration enantiomers could not be separated normally.

[0077] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for the HPLC detection of the enantiomers of Elafibranor hydrochloride, characterized in that, The method comprises the following steps: Preparation of a test sample solution by dissolving the test hydrochloric acid igliflozin in a diluent; Detection of the test sample solution by normal phase high performance liquid chromatography (HPLC); The stationary phase of the normal phase HPLC is silica gel with cellulose-tris(3-chloro-4-methylphenylcarbamate) covalently bonded on the surface. The mobile phase of the normal phase HPLC is a mixture of n-hexane, isopropyl alcohol, trifluoroacetic acid and diethylamine.

2. The HPLC method for the detection of the enantiomers of Elafibranor hydrochloride according to claim 1, characterized in that, The diluent is ethanol.

3. The HPLC method for the detection of the enantiomers of Elafibranor hydrochloride according to claim 1, characterized in that, The concentration of the test sample solution is 0.4-1 mg / mL.

4. The HPLC method for detecting the enantiomers of Elafibranor hydrochloride according to claim 1, characterized in that, The volume ratio of n-hexane, isopropyl alcohol, trifluoroacetic acid and diethylamine is (78-82) : (18-22) : (0.08-0.12) : (0.015-0.025).

5. The HPLC method for the detection of the enantiomers of Elafibranor hydrochloride according to claim 4, characterized in that, The volume ratio of n-hexane, isopropyl alcohol, trifluoroacetic acid and diethylamine is 80:20:0.1:0.

02.

6. The HPLC method for the detection of the enantiomers of Elafibranor hydrochloride according to claim 1, characterized in that, The stationary phase of the normal phase HPLC is a CHIRALPAK IM chromatographic column.

7. The HPLC method for the detection of the enantiomers of Elafibranor hydrochloride according to claim 6, characterized in that, The CHIRALPAK IM chromatographic column has a length of 150 mm, an inner diameter of 4.6 mm, and a particle size of 5 μm.

8. The HPLC method for the detection of enantiomeric impurities of Elafibranor hydrochloride according to claim 1, characterized in that, The column temperature of the normal phase HPLC is 30-40℃, the detection wavelength is 230-245 nm, the flow rate is 0.8-1.2 mL / min, and the injection volume is 0.3-0.6 μL.

9. The HPLC method for the detection of the enantiomers of Elafibranor hydrochloride according to claim 8, characterized in that, The column temperature of the normal phase HPLC is 33-37℃, and the detection wavelength is 240 nm.

10. Use of the HPLC detection method of the enantiomers of hydrochloric acid igliflozin according to any one of claims 1-9 in the quality control of hydrochloric acid igliflozin pharmaceutical preparations.

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