Method for detecting polymer in lipoic acid injection

Abstract

The invention provides a method for detecting a polymer in a lipoic acid injection, which adopts a liquid chromatography-mass spectrometry detection method to qualitatively detect and analyze the impurities of the polymer in the lipoic acid injection, and adopts a high performance liquid chromatography to quantitatively detect and analyze the impurities of the polymer and quantitatively confirm the impurities of the polymer through nuclear magnetism. According to the detection method disclosed by the invention, polymer impurities, including lipoic acid and at least seven common impurities, in the lipoic acid injection can be separated in a high performance liquid chromatogram and are quantitatively determined; the method is high in accuracy, good in specificity, high in analysis speed, stable in linear relation and good in reproducibility, qualitative and quantitative quality detection and monitoring of the lipoic acid injection are facilitated, stable quality and safety of the lipoic acid injection are guaranteed, and application and popularization are facilitated.

Description

Technical Field

[0001] This invention relates to the fields of drug analysis and testing and pharmaceutical quality control, and in particular to a method for detecting polymers in thioctic acid injection. Background Technology

[0002] With changes in people's dietary habits and lifestyles, the incidence of diabetes has gradually increased in recent years. Alpha-lipoic acid (ALA) is a coenzyme found in mitochondria with a high free radical scavenging capacity, capable of eliminating free radicals in the body and possessing anti-inflammatory and anti-aging effects. It is currently widely used in the prevention and treatment of heart disease, diabetes, liver disease, and Alzheimer's disease. Statistics show that there are approximately 150-200 million people with diabetes worldwide, with nearly 100 million in China, severely impacting people's quality of life. Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, and its pathogenesis is irreversible, making it a high-risk factor for diabetic foot and infections. ALA can inhibit lipid oxidation in nerve tissue, hinder protein glycosylation, inhibit aldose reductase, and prevent the formation of sorbitol from glucose or galactose. Toxicological experiments have shown that this drug can prevent the progression of diabetes, promote glucose utilization, and prevent neuropathy caused by hyperglycemia.

[0003] Thioctanoic acid injection is unstable and prone to polymer impurities, which are often complex in state. The polymer control method listed in the European Pharmacopoeia is thin-layer chromatography, a semi-quantitative detection and control method that cannot accurately quantify individual polymer impurities. Furthermore, some published methods for detecting polymer impurities in thioctic acid drugs can qualitatively identify several polymers and multiple polymer impurity peaks in thioctic acid drug formulations; however, these methods only provide qualitative analysis of the polymers and do not offer quantitative analytical methods. Moreover, thioctic acid injection is a liquid formulation, making it even more susceptible to polymer impurities. These polymer impurities can affect the safety of the formulation. Therefore, a detection and control method that can accurately identify and quantify polymer impurities in this formulation is needed for effective control. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for detecting polymers in thioctic acid injection. This method involves qualitative analysis of various polymer impurities in thioctic acid injection samples and quantitative analysis and control of impurities using the external standard method of the main component.

[0005] To achieve the above objectives, the present invention provides a method for detecting polymers in thioctic acid injection. The method employs liquid chromatography-mass spectrometry (LC-MS) for qualitative analysis of polymer impurities in the thioctic acid injection, and high-performance liquid chromatography (HPLC) for quantitative analysis and nuclear magnetic resonance (NMR) confirmation of the polymer impurities; thereby effectively controlling the content of polymer impurities in the thioctic acid injection.

[0006] Furthermore, the polymerization mode and molecular weight of the polymer in the thioctic acid injection were detected and analyzed using a dual quadrupole mass spectrometer (LC-MS).

[0007] The dual quadrupole mass spectrometer is a Shimadzu LCMS-MS-8040 dual quadrupole mass spectrometer; the chromatographic column is a C18 chromatographic separation column packed with octadecylsilane-bonded silica gel, and the particle size of the chromatographic column packing is 2.5 μm to 4.5 μm;

[0008] Preferably, the chromatographic column is a Waters XSelect CSH column. TM C18 (4.6mm × 150mm, particle size 3.5μm).

[0009] Preferably, formic acid solution is used as mobile phase A, and a mixture of methanol, acetonitrile and tetrahydrofuran is used as mobile phase B;

[0010] Preferably, the formic acid solution concentration is 0.05% to 0.15%; the formic acid solution concentration is 0.1%, and the mobile phase B is methanol-acetonitrile-tetrahydrofuran in a ratio of (500:400:100);

[0011] Furthermore, the chromatographic conditions were as follows: flow rate (1.0 ml / min ± 0.1 ml / min), column temperature (35℃ ± 2℃), and initial mobile phase ratio (95:5 / 85:15).

[0012] Preferably, the flow rate is 1 ml / min; the column temperature is 35°C; the injection chamber temperature is 6°C; the detection wavelength is 241 nm; the injection volume is 40 μl; and gradient elution is performed (a trapping column is installed between the gradient mixer and the autosampler).

[0013] The gradient change in the gradient elution is as follows:

[0014]

[0015] Furthermore, the high-performance liquid chromatograph is an Agilent 1260, and the chromatographic column is a C18 chromatographic separation column packed with octadecylsilane-bonded silica gel, with a particle size of 2.5 μm to 4.5 μm; the chromatographic column is a WatersXSelect CSH column. TMC18 (4.6mm × 150mm, particle size 3.5μm);

[0016] Furthermore, the chromatographic conditions were as follows: flow rate (1.0 ml / min ± 0.1 ml / min), column temperature (35℃ ± 2℃), and initial mobile phase ratio (95:5 / 85:15).

[0017] Preferably, 0.1% formic acid solution is used as mobile phase A, and methanol-acetonitrile-tetrahydrofuran (500:400:100) is used as mobile phase B, with a flow rate of 1 ml / min; column temperature is 35℃; injection chamber temperature is 6℃; detection wavelength is 241 nm; injection volume is 80 μl; gradient elution is performed (a trapping column is installed between the gradient mixer and the autosampler);

[0018] The gradient change in the gradient elution is as follows:

[0019]

[0020] The purpose of this invention is to qualitatively detect and analyze polymeric impurities in thioctic acid injection using liquid chromatography-mass spectrometry (LC-MS) and quantitatively detect and analyze polymeric impurities using high-performance liquid chromatography (HPLC); and to prepare polymeric impurities with high content, such as dimers and trimers, thereby effectively controlling the content of polymeric impurities in thioctic acid injection.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The detection method provided by this invention can separate and quantitatively determine polymeric impurities, including lipoic acid and at least seven common impurities, in thioctic acid injection using high-performance liquid chromatography (HPLC). By selecting optimal conditions, the sensitivity and accuracy of the detection of each component are further improved. The specificity, accuracy, repeatability, precision, limit of quantitation, limit of detection, linearity, stability, and robustness of the chromatographic conditions of this detection method have been thoroughly validated. This method exhibits high accuracy, good specificity, fast analysis speed, stable linearity, and good reproducibility, facilitating qualitative and quantitative quality detection and monitoring of thioctic acid injection, ensuring the quality stability and safety of thioctic acid injection, and promoting its widespread application. Attached Figure Description

[0023] Figure 1 The specific synthesis chromatogram of liquid chromatography for the detection method of polymers in thioctic acid injection of the present invention;

[0024] Figure 2 HPLC chromatogram of blank solvent in the detection method of the present invention;

[0025] Figure 3 The sensitivity solution HPLC chromatogram of the detection method of the present invention;

[0026] Figure 4 HPLC chromatogram of blank excipient solution for the detection method of the present invention;

[0027] Figure 5 HPLC chromatogram of the reference solution of the detection method of the present invention;

[0028] Figure 6 HPLC chromatogram of the test solution in the detection method of the present invention;

[0029] Figure 7 Linear relationship diagram of dimer in the test solution of the detection method of the present invention;

[0030] Figure 8 Linear relationship diagram of trimer in the test solution of the detection method of the present invention;

[0031] Figure 9 Typical HPLC chromatograms of dimers and trimers in the test solution of the detection method of the present invention;

[0032] Figure 10 The LC / MS test results of the polymer impurity qualitative analysis of the test sample using the detection method of the present invention are shown in the chromatogram. Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments, so that those skilled in the art can fully understand the technical content of this invention. It should be noted that the specific embodiments described herein are only for explaining this invention and are not intended to limit this invention.

[0034] Example 1:

[0035] In a specific implementation scheme, the detection method of the present invention is implemented using the following steps:

[0036] LC-MS was used to detect and analyze the possible polymer polymerization modes and molecular weights in thioctic acid injection.

[0037] Instruments and materials:

[0038] Shimadzu LCMS-MS-8040 dual quadrupole mass spectrometer; UV detector, Waters XSelectCSH column. TM C18 (4.6mm×150mm, 3.5μm), analytical balance of 1 / 100,000, pipettes (1ml, 2ml), volumetric flasks (10ml, 100ml), vortex mixer, graduated cylinders (50ml, 10ml) one each, disposable droppers, several 100ml conical flasks, markers and labels, etc.

[0039] Samples and reagents:

[0040] Thioctic acid injection, methanol, acetonitrile, tetrahydrofuran, formic acid, purified water;

[0041] Chromatographic conditions:

[0042] Using octadecylsilane-bonded silica gel as a filler (Waters XSelect CSH) TM (C18, 4.6 mm × 150 mm, 3.5 μm or equivalent column); mobile phase A: 0.1% formic acid solution; mobile phase B: methanol-acetonitrile-tetrahydrofuran (500:400:100); gradient elution according to Table 101 (with a trapping column installed between the gradient mixer and the autosampler); flow rate: 1 ml / min; column temperature: 35 °C; injection chamber temperature: 6 °C; detection wavelength: 241 nm; injection volume: 40 μl.

[0043] Table 101 Gradient Elution

[0044]

[0045] Example 2:

[0046] The specific implementation steps of this detection method are as follows:

[0047] Instruments and materials

[0048] High-performance liquid chromatograph (Agilent 1260), Waters XSelect CSH column TM C18 (4.6mm×150mm, 3.5μm), analytical balance of 1 / 1 million, analytical balance of 1 / 100,000, pipettes (1ml, 2ml), volumetric flasks (5ml, 10ml, 20ml, 25ml, 50ml), vortex mixer, graduated cylinders (50ml, 1L) one each, disposable droppers, several 100ml conical flasks, markers and labels, etc.

[0049] Samples and reagents

[0050] Thioctanoic acid injection, thioctic acid reference standard, thioctic acid dimer reference standard, thioctic acid trimer reference standard, blank excipients, methanol, acetonitrile, tetrahydrofuran, formic acid, purified water

[0051] Chromatographic conditions

[0052] Using octadecylsilane-bonded silica gel as a filler (Waters XSelect CSH) TM(C18, 4.6 mm × 150 mm, 3.5 μm or equivalent column); mobile phase A: 0.1% formic acid solution; mobile phase B: methanol-acetonitrile-tetrahydrofuran (500:400:100); gradient elution according to Table 102 (with a trapping column installed between the gradient mixer and the autosampler); flow rate: 1 ml / min; column temperature: 35 °C; injection chamber temperature: 6 °C; detection wavelength: 241 nm; injection volume: 80 μl.

[0053] Table 102 Gradient Change Elution

[0054]

[0055] (1) Solution preparation

[0056] Test solution: Accurately measure an appropriate amount of this product and dilute it with water to prepare a solution containing approximately 5 mg of thioctic acid per 1 ml;

[0057] (2) Operation process

[0058] Accurately measure 40 μl of the test solution and inject it into the liquid chromatography-mass spectrometry (LC-MS) instrument; record the chromatogram.

[0059] (3) Results

[0060] The liquid chromatography-mass spectra of the self-made formulation and the qualitative results of polymer impurities in Table 103 were obtained.

[0061] Method validation was performed using polymer reference standards:

[0062] Dimers and trimers were obtained by preparing and separating thioctic acid injection solution, and their structures were confirmed and quantitatively verified by NMR.

[0063] Table 103 Qualitative results of polymer impurity testing using LC / MS.

[0064] .

[0065] Verification Example 1:

[0066] The present invention discloses a method for detecting polymers in thioctic acid injection, and the specificity verification of this method is as follows:

[0067] (1) Solution preparation,

[0068] The specific solution preparation is shown in Table 1.

[0069] Table 1 Preparation of specific solutions

[0070]

[0071] (2) Acceptable standards

[0072] 1) Blank solution and blank excipient have no interference with the determination of impurities with a relative retention time of approximately 1.35 and beyond.

[0073] 2) The ratio of the retention times of dimers and trimers in the test solution to those in the positioning solution is consistent (between 0.95 and 1.05).

[0074] (3) Results and Conclusions

[0075] Accurately measure 80 μl of each specific solution listed in Table 1 above, inject it into the liquid chromatograph, and record the chromatogram. See the schematic diagram of specificity. Figure 1 The results of the specificity test are shown in Table 2.

[0076] Table 2 Results of specificity test

[0077]

[0078] Note: Impurities A to J are other specific impurities besides the polymer.

[0079] Conclusion: 1) Blank solution and blank excipient do not interfere with the determination of impurities with a relative retention time of approximately 1.35 and beyond.

[0080] 2) The retention times of dimers and trimers in the test solution and those in the positioning solution were 1.00 and 1.00, respectively, both within the range of 0.95 to 1.05, which meets the requirements. This detection method has good specificity.

[0081] Verification Example 2:

[0082] The present invention discloses a method for detecting polymers in thioctic acid injection, and verifies the accuracy of the detection method as follows:

[0083] (1) Solution preparation

[0084] The accuracy of solution preparation is shown in Table 3.

[0085] Table 3 Accuracy Solution Preparation

[0086]

[0087] (2) Acceptable standards

[0088] 1) Under the LOQ concentration test, the spiked recoveries (1*3 samples) were all between 70.0% and 130.0%, and the RSD of the 3-shot recoveries was ≤15.0%;

[0089] 2) At the other three concentrations (3*3 samples), the spiked recoveries were all between 80.0% and 120.0%, and the RSD of the 9-needle recovery was ≤10.0%.

[0090] (3) Results and Conclusions

[0091] Accurately measure 80 μl of each of the above solutions, inject them into the liquid chromatograph, record the chromatogram, calculate the recovery rate and relative standard deviation (RSD) of dimer and trimer in the three test solutions at the LOQ concentration, and calculate the recovery rate and relative standard deviation (RSD) of dimer and trimer in the nine test solutions at the other three concentrations. The accuracy results of this detection method are shown in Tables 4 and 5.

[0092] Table 4. Accuracy Results of Polymer Dimers

[0093]

[0094] Table 5 Accuracy Results of Polymer Trimers

[0095]

[0096] Conclusion: The recovery rates at all concentrations met the requirements, and the accuracy of the detection method was good.

[0097] Verification Example 3:

[0098] The present invention provides a method for detecting polymers in thioctic acid injection, and verifies the repeatability of this method:

[0099] (1) Solution preparation

[0100] The preparation of repeatable solutions is shown in Table 6.

[0101] Table 6. Preparation of Repeatable Solutions

[0102]

[0103] (2) Acceptable standards

[0104] The relative standard deviation (RSD) requirements for the total amount of impurities with a relative retention time of approximately 1.35 and beyond in the six test sample solutions are as follows (X represents the total amount of impurities with a relative retention time of approximately 1.35 and beyond in the test sample solution): RSD ≤ 5.0%.

[0105] (3) Results and Conclusions

[0106] Accurately measure 80 μl of each of the above solutions, inject them into the liquid chromatograph, record the chromatograms, and calculate the total amount of impurities with relative retention times of approximately 1.35 and beyond in the test solution, as well as the relative standard deviation (RSD) of the total amount of impurities in the six test solutions, using the principal component external standard method with correction factors. The results of this detection method are shown in Table 7.

[0107] Table 7. Precision-Repeatability Test Results

[0108]

[0109] Conclusion: The average total impurity content in the six test sample solutions was 0.6%, and the RSD was 1.0%, all of which met the requirements, indicating that the detection method had good repeatability.

[0110] Verification Example 4:

[0111] The present invention discloses a method for detecting polymers in thioctic acid injection, and the intermediate precision verification of this method is as follows:

[0112] Using the same batch of test samples, two testers determined the total amount of impurities in six test samples with a relative retention time of approximately 1.35 and beyond at different dates and using different instruments.

[0113] (1) Solution preparation

[0114] The intermediate precision solution is prepared as shown in Table 8.

[0115] Table 8 Preparation of intermediate precision solutions

[0116]

[0117] (2) Acceptable standards

[0118] 1) The RSD of the total amount of impurities with a relative retention time of approximately 1.35 and beyond in the 6 test solutions of test personnel 2 should meet the repeatability requirements.

[0119] 2) The RSD requirements for the total amount of impurities with a relative retention time of approximately 1.35 and beyond in the 12 test solutions prepared by the two testers are as follows (X represents the total amount of impurities with a relative retention time of approximately 1.35 and beyond in the test solution): RSD ≤ 5.0%;

[0120] (3) Results and Conclusions

[0121] Accurately measure 80 μl of each of the above solutions and inject them into the liquid chromatograph. Record the chromatograms and calculate the relative standard deviation (RSD) of the total amount of impurities with a relative retention time of approximately 1.35 and beyond in the six test solutions of Experimenter 2. Simultaneously, calculate the RSD of the total amount of impurities with a relative retention time of approximately 1.35 and beyond in the 12 test solutions of both experimenters. Examine the intermediate precision of this method. The repeatability results for Experimenter 2 are shown in Table 9, and the intermediate precision test results are shown in Table 10.

[0122] Table 9 Precision - Repeatability Results by Testers

[0123]

[0124] Table 10 Results of Precision-Intermediate Precision Tests

[0125]

[0126] Conclusion: The average content of impurities with relative retention times of approximately 1.35 and beyond in the 12 test sample solutions was 0.6%, with an RSD of 2.2%, all meeting the requirements. The intermediate precision results of this detection method meet the requirements, indicating good precision of the method.

[0127] Verification Example 5:

[0128] The present invention discloses a method for detecting polymers in thioctic acid injection, and the limit of quantitation verification of this method is as follows:

[0129] (1) Solution preparation

[0130] The preparation of the limit-of-quantity solution is shown in Table 11.

[0131] Table 11 Preparation of solutions with limit of quantitation

[0132]

[0133] (2) Acceptable standards

[0134] 1) The signal-to-noise ratio (S / N) of the lipoic acid peak and each impurity peak is ≥10;

[0135] 2) The RSD of the peak area of ​​thioctic acid and each impurity peak in its 6 limit of quantitation solutions is ≤10.0%.

[0136] (3) Results and Conclusions

[0137] Accurately measure 80 μl of each of the above solutions, inject them into the liquid chromatograph, record the chromatograms, and calculate the RSD and signal-to-noise ratio of the peak areas of thioctic acid and impurity peaks in the 6 limit-of-quantity solutions. The results of this detection method are shown in Tables 12-14.

[0138] Table 12 Results of Limit of Quantitation Test for Lipoic Acid

[0139]

[0140] Table 13 Results of Limit of Quantitative Test for Dimer

[0141]

[0142] Table 14 Results of Trimer Limit of Quantitation Test

[0143]

[0144] Conclusion: The quantitation limits for thioctic acid and various polymer impurities detected by this method meet the detection requirements.

[0145] Verification Example 6:

[0146] The present invention discloses a method for detecting polymers in thioctic acid injection, and the detection limit of this method is verified as follows:

[0147] (1) Solution preparation

[0148] The preparation of the detection limit solution is shown in Table 15.

[0149] Table 15 Preparation of Detection Limit Solutions

[0150]

[0151] (2) Acceptable standards

[0152] The signal-to-noise ratio (S / N) of the thioctic acid peak and each impurity peak is ≥3.

[0153] (3) Results and Conclusions

[0154] Accurately measure 80 μl of each of the above solutions, inject them into the liquid chromatograph, record the chromatograms, and statistically analyze the signal-to-noise ratio of the thioctic acid peak and impurity peaks in the three solutions at the detection limit. The results are shown in Table 16.

[0155] Table 16 Results of the detection limit test

[0156]

[0157] Conclusion: The detection method of the present invention has high detection limit sensitivity and meets the detection requirements.

[0158] Verification Example 7:

[0159] The present invention discloses a method for detecting polymers in thioctic acid injection, and verifies the linearity of this detection method:

[0160] (1) Solution preparation

[0161] The preparation of linear solutions is shown in Table 17.

[0162] Table 17 Preparation of Linear Solutions

[0163]

[0164] (2) Acceptable standards

[0165] 1) The correlation coefficient (r) of the linear regression equation is ≥0.990;

[0166] 2) The Y-intercept should be within 25% of the 100% response value, and the relative standard deviation of the response factor (A / C) should not exceed 10.0%;

[0167] 3) Visual observation of the residual curve showed no obvious trend change.

[0168] (3) Results and Conclusions

[0169] Accurately measure 80 μl of each of the above linear solutions and inject them into the liquid chromatograph. Record the chromatograms and plot the linear regression equation with concentration on the x-axis and peak area on the y-axis. The linearity results of this detection method are shown in Table 18.

[0170] Table 18 Linearity Results

[0171]

[0172] Conclusions: The detection method showed good linearity for lipoic acid in the range of 0.5 μg / ml to 75 μg / ml; the detection method also showed good linearity for the dimer in the range of 0.5 μg / ml to 75 μg / ml, with a correction factor of 0.61; the detection method also showed good linearity for the trimer in the range of 0.5 μg / ml to 75 μg / ml, with a correction factor of 0.63.

[0173] Verification Example 8:

[0174] The present invention discloses a method for detecting polymers in thioctic acid injection, and verifies the solution stability of this method:

[0175] (1) Solution preparation

[0176] The preparation of stable solutions is shown in Table 19.

[0177] Table 19 Preparation of Stability Solutions

[0178]

[0179] (3) Acceptable standards

[0180] Table 20 Acceptable Standards

[0181]

[0182] (4) Results and Conclusions

[0183] Take the above reference solution and place it under refrigeration (6℃) for 0, 29, 52, and 56 hours, and under room temperature for 0, 30, and 51 hours. Accurately measure 80 μl of each solution and inject it into the liquid chromatograph. Record the chromatograms and calculate the ratio of the peak area measured at each time point to the peak area at 0 hours. Take the above test solution and place it under refrigeration (6℃) for 0, 10, 20, and 26 hours, and under room temperature for 0, 3, and 21 hours. Accurately measure 80 μl of each solution and inject it into the liquid chromatograph. Record the chromatograms and calculate the RD value of the total impurities measured at each time point to the total impurities at 0 hours. The results are shown in Table 21.

[0184] Table 21 Durability-Stability Results

[0185]

[0186] Conclusion: The reference solution was stable for 56 hours under refrigeration (6℃) and for 51 hours at room temperature; the test solution was stable for 26 hours under refrigeration (6℃) and for 21 hours at room temperature.

[0187] Verification Example 9:

[0188] The present invention discloses a method for detecting polymers in thioctic acid injection, wherein the robustness of the chromatographic conditions for this detection method is verified as follows:

[0189] (1) Solution preparation

[0190] The preparation of the durability solution is shown in Table 22.

[0191] Table 22 Preparation of Durability Solution

[0192]

[0193] (2) Acceptable standards

[0194] 1) The system's applicability under all conditions should meet the requirements;

[0195] 2) Under all conditions, the changes in the total amount of impurities in the test solution with a relative retention time of approximately 1.35 and beyond are required as follows (X represents the total amount of impurities in the test solution with a relative retention time of approximately 1.35 and beyond): RSD ≤ 10.0%;

[0196] (3) Results and conclusions: The results are summarized in Table 23.

[0197] Table 23 Summary of Durability Results

[0198]

[0199] Conclusion: The chromatographic conditions showed good robustness under varying flow rates (1.0 ml / min ± 0.1 ml / min), column temperatures (35℃ ± 2℃), initial mobile phase ratios (95:5 / 85:15), and different column types.

[0200] The RSD of the total impurities in the test solution determined by this detection method under various conditions is 0, less than 10.0%; the chromatographic conditions are robust.

[0201] It should be noted that the above preferred embodiments are merely illustrative of the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A method for detecting polymers in thioctic acid injection, characterized in that: The polymer impurities in thioctic acid injection were qualitatively detected and analyzed using liquid chromatography-mass spectrometry (LC-MS), and quantitatively detected and confirmed by high performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR).

2. The method for detecting polymers in thioctic acid injection according to claim 1, characterized in that: The polymerization mode and molecular weight of the polymer in the thioctic acid injection solution were detected and analyzed using a dual quadrupole mass spectrometer (LC-MS).

3. The method for detecting polymers in thioctic acid injection according to claim 2, characterized in that: The dual quadrupole mass spectrometer is a Shimadzu LCMS-MS-8040 dual quadrupole mass spectrometer; the chromatographic column is a C18 chromatographic separation column packed with octadecylsilane-bonded silica gel.

4. The method for detecting polymers in thioctic acid injection according to claim 3, characterized in that: The particle size of the chromatographic column packing is 2.5 μm to 4.5 μm.

5. The method for detecting polymers in thioctic acid injection according to claim 3, characterized in that: Formic acid solution was used as mobile phase A, and a mixture of methanol, acetonitrile and tetrahydrofuran was used as mobile phase B.

6. The method for detecting polymers in thioctic acid injection according to claim 5, characterized in that: The formic acid solution concentration is 0.05% to 0.15%.

7. The method for detecting polymers in thioctic acid injection according to any one of claims 3 to 6, characterized in that: Chromatographic conditions were set at a flow rate of 1.0 ml / min ± 0.1 ml / min, a column temperature of 35℃ ± 2℃, and an initial mobile phase ratio of 95:5 to 85:15, with gradient elution.

8. The method for detecting polymers in thioctic acid injection according to claim 7, characterized in that: The gradient change in the gradient elution is as follows: 。 9. The method for detecting polymers in thioctic acid injection according to claim 1, characterized in that: The high-performance liquid chromatograph is an Agilent 1260, and the chromatographic column is a C18 chromatographic separation column packed with octadecylsilane-bonded silica gel.

10. The method for detecting polymers in thioctic acid injection according to claim 9, characterized in that: The chromatographic column packing material has a particle size of 2.5 μm to 4.5 μm; the chromatographic conditions are a flow rate of 1.0 ml / min ± 0.1 ml / min, a column temperature of 35℃ ± 2℃, and an initial mobile phase ratio of 95:5 to 85:15, with gradient elution.

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