A method and system for determining impurities in methanesulfonic acid

Abstract

The application discloses a kind of impurity determination method and system in methyl sulfonic acid, it is related to impurity determination technical field, including the following steps: taking methyl sulfonic acid sample 200mg with sodium bicarbonate 175mg, be placed in same 20mL measuring flask;Dimethyl sulfoxide is added as solvent to the measuring flask, ultrasonic treatment 5 minutes to dissolve reactant, so that methyl sulfonic acid and sodium bicarbonate occur reaction to generate volatile impurities and remove methyl sulfonic acid.The application removes acidic component by neutralization reaction of methyl sulfonic acid and sodium bicarbonate, avoids gas chromatograph corrosion;Constant temperature heating program is used to prevent high temperature decomposition interference, to ensure detection stability;Optimized chromatographic column and condition are used to realize impurity high-efficiency separation, peak shape is clear, and separation degree is good;And through high-purity dimethyl sulfoxide system and ultrasonic auxiliary reaction, reduce noise, improve sensitivity and repeatability, realize the rapid, accurate, high-stable detection of impurities in methyl sulfonic acid.

Description

A method and system for determining impurities in methanesulfonic acid Technical Field

[0001] This invention relates to the field of impurity determination technology, and specifically to a method and system for determining impurities in methanesulfonic acid. Background Technology

[0002] Methanesulfonic acid (MSA) is a strong acid widely used in pharmaceutical formulation development due to its ability to form stable salts with various basic drugs. Through salt formation, methanesulfonates significantly improve the water solubility and bioavailability of drugs, while also exhibiting low hygroscopicity and high storage stability, thus holding significant value in the pharmaceutical industry. However, methanesulfonic acid typically participates in reactions later in the drug synthesis process, and its purity and impurity control directly affect the quality and safety of the final drug. High impurity levels in methanesulfonic acid may lead to impurity content exceeding pharmacopoeia or regulatory requirements after salt formation, thereby affecting drug application and market launch. Therefore, the detection and control of methanesulfonic acid impurities is a critical aspect of the drug quality management system.

[0003] The existing technology has the following shortcomings:

[0004] Current research primarily focuses on methods for determining the content of methanesulfonic acid, with limited research on its impurity detection. Existing methods often employ silane-based derivatizing reagents for post-derivatization analysis, which suffers from long reaction times, incomplete derivatization, numerous byproducts, and interference with impurity detection. Considering the physicochemical properties of methanesulfonic acid, its strong acidity leads to corrosiveness to metal components, and it is easily decomposed at high temperatures, making it unsuitable for gas chromatography detection. Furthermore, its impurities are mostly small-molecule sulfide compounds without UV absorption, also unsuitable for conventional liquid chromatography. Therefore, existing detection methods are insufficient to meet the need for rapid, accurate, and effective detection of impurities in methanesulfonic acid. There is an urgent need to develop a simple, sensitive, and highly selective method suitable for methanesulfonic acid systems to improve the quality control of pharmaceutical raw materials and intermediates.

[0005] The information disclosed in the background section is only intended to enhance the understanding of the background of this disclosure, and therefore may include information that does not constitute prior art known to those skilled in the art. Summary of the Invention

[0006] The purpose of this invention is to provide a method and system for determining impurities in methanesulfonic acid, so as to solve the problems in the background art mentioned above.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a system for determining impurities in methanesulfonic acid, comprising a sample weighing and mixing module, a neutralization reaction module, a test sample preparation module, a reference standard preparation module, and a gas chromatography detection module, wherein the neutralization reaction module includes a bubble removal and system homogenization unit, a static layering and liquid stabilization unit, an inert gas purification unit, and a precision filtration and sample purification unit.

[0008] In the sample weighing and mixing module, weigh 200 mg of methanesulfonic acid sample and 175 mg of sodium bicarbonate and place them in the same 20 mL volumetric flask.

[0009] In the neutralization reaction module, dimethyl sulfoxide is added to the vector bottle as a solvent, and the reactants are dissolved by ultrasonic treatment for 5 minutes, so that methanesulfonic acid reacts with sodium bicarbonate to generate volatile impurities and remove methanesulfonic acid.

[0010] The bubble removal and system homogenization unit, after the ultrasonic reaction is completed, immediately performs low-speed rotational stirring after the carbon dioxide generated in the reaction system is completely released, so that the salt byproducts generated by the reaction of methanesulfonic acid and sodium bicarbonate are fully dispersed in the dimethyl sulfoxide system. Continuous stirring promotes the complete removal of bubbles and forms a homogeneous reaction system.

[0011] The static stratification and liquid stabilization unit seals and allows the stirred and homogenized reaction system to settle, enabling microbubbles and unreacted particles in the system to gradually settle. The stratification effect stabilizes the system structure, and a clear and uniform reaction liquid is formed in the upper layer, providing a stable medium for subsequent purification treatment.

[0012] The inert gas purification unit slowly introduces the upper layer of reaction liquid formed by standing into the inert nitrogen gas flow, so that the inert nitrogen gas replaces the reaction liquid, removes residual volatile impurities and solvent vapors, and forms an inert protective environment on the surface of the system, further purifying the structure of the reaction liquid.

[0013] The precision filtration and sample purification unit slowly filters the upper reaction liquid after nitrogen replacement through a 0.22-micron organic filter membrane to remove residual salt particles and fine suspended matter in the system, resulting in a stable, transparent sample system free from impurities. This provides ideal injection conditions with low noise and low baseline fluctuation for gas chromatography detection.

[0014] The test sample preparation module, after ultrasonic dissolution, adds dimethyl sulfoxide to the mark to obtain the test sample solution;

[0015] In the reference standard preparation module, 20 mg each of methyl sulfide and dimethyl disulfide were weighed, dissolved and diluted with dimethyl sulfoxide, and prepared into a reference standard solution containing approximately 10 μg each of methyl sulfide and dimethyl disulfide per 1 mL.

[0016] The gas chromatography detection module uses gas chromatography for detection. The test solution and the reference solution are injected separately and separated on a capillary column with 6% cyanopropylphenyl-94% dimethyl polysiloxane as the stationary phase. The initial temperature is set to 40℃ and held for 5 minutes, then increased to 180℃ at a rate of 30℃ per minute and held for 5 minutes. The injection port temperature is 180℃, the detector temperature is 230℃, the injection volume is 0.5μL, and the split ratio is 10:1. The content of methyl sulfide, dimethyl disulfide, and unknown impurities in methanesulfonic acid is determined by comparing the chromatograms.

[0017] Preferably, the molar ratio of methanesulfonic acid to sodium bicarbonate is controlled between 1:1.5 and 1:2.0 to ensure that methanesulfonic acid can be completely neutralized, while avoiding excessive sodium bicarbonate residue from interfering with subsequent gas chromatography detection. During the ultrasonic reaction, the ultrasonic frequency is controlled between 40 kHz and 60 kHz, and the reaction temperature is maintained at 25℃ ± 2℃. By controlling the isothermal ultrasonic conditions, the reaction between methanesulfonic acid and sodium bicarbonate can be effectively promoted to be complete, improving the efficiency of impurity release, thereby making the detection signal more stable and repeatable, and ensuring the accuracy and reproducibility of impurity quantitative analysis.

[0018] Preferably, after the test solution undergoes reaction, the generated carbonate precipitate can be removed by centrifugation, and the supernatant is then used as the injection solution for detection. The centrifugation speed is 8000 to 10000 rpm, and the time is 3 to 5 minutes to remove insoluble salt impurities. This step can significantly reduce the risk of contamination of the injection system, reduce baseline drift of the chromatographic column, improve the stability and peak symmetry of the detection system, thereby improving the detection sensitivity and peak resolution for trace thioether impurities in methanesulfonic acid.

[0019] Preferably, the carrier gas for gas chromatography is high-purity helium with a purity of not less than 99.999%, and the carrier gas flow rate is controlled between 1.0 and 1.2 mL / min. The detector is a flame ionization detector (FID). During the detection process, by optimizing the inner diameter of the inlet liner and the split ratio, the accumulation of methanesulfonic acid reaction residues is effectively prevented, thereby improving the instrument's durability and detection linear range. This invention significantly improves the impurity separation effect by optimizing the carrier gas and detection conditions, enabling methyl sulfide, dimethyl disulfide, and potentially unknown impurities to be completely separated within 12 minutes, with a resolution greater than 2.0.

[0020] Preferably, the reference solution may further include trimethyl sulfide or ethyl methyl sulfide as an external standard to verify the separation capability and response linearity of the detection system; the concentration of the reference standard is controlled between 5 and 20 μg / mL, and a response factor calibration curve is established using the external standard method to ensure the traceability and quantitative accuracy of the detection results. Using a multi-component external standard can achieve calibration stability in different test batches, thereby improving the robustness and methodological consistency of the method, making the method scalable in drug quality research and process control.

[0021] Preferably, the gas chromatography column is a 6% cyanopropylphenyl-94% dimethyl polysiloxane capillary column with a length of 30m, an inner diameter of 0.25mm, and a film thickness of 0.25μm; by controlling the heating rate and column temperature equilibration time, the impurity peaks can be fully displayed and separated from the solvent peaks, avoiding co-eluenting.

[0022] Preferably, the column temperature reproducibility is within ±0.5℃ during the detection process through automated temperature program control, thereby ensuring that the repeatability of impurity retention time is better than 0.1 minutes. This technical solution can achieve high-resolution impurity detection in a short time and has a significant improvement in detection efficiency.

[0023] Preferably, the dimethyl sulfoxide solvent has a purity of not less than 99.9% and is filtered through a 0.22 μm filter membrane to remove trace particulate matter and prevent contamination of the chromatographic system.

[0024] Preferably, the solution maintains stability at room temperature for at least 48 hours and has a relative standard deviation (RSD) of less than 2.0% for the peak area, thereby ensuring the reliability of the detection process. The use of this high-purity solvent not only effectively improves the detection sensitivity but also reduces solvent background noise interference, which has significant advantages for the quantification of trace sulfide impurities.

[0025] A system for determining impurities in methanesulfonic acid includes a sample weighing and mixing module, a neutralization reaction module, a test sample preparation module, a reference standard preparation module, and a gas chromatography detection module.

[0026] In the sample weighing and mixing module, weigh 200 mg of methanesulfonic acid sample and 175 mg of sodium bicarbonate and place them in the same 20 mL volumetric flask.

[0027] In the neutralization reaction module, dimethyl sulfoxide is added to the vector bottle as a solvent, and the reactants are dissolved by ultrasonic treatment for 5 minutes, so that methanesulfonic acid reacts with sodium bicarbonate to generate volatile impurities and remove methanesulfonic acid.

[0028] The test sample preparation module, after ultrasonic dissolution, adds dimethyl sulfoxide to the mark to obtain the test sample solution;

[0029] In the reference standard preparation module, 20 mg each of methyl sulfide and dimethyl disulfide were weighed, dissolved and diluted with dimethyl sulfoxide, and prepared into a reference standard solution containing approximately 10 μg each of methyl sulfide and dimethyl disulfide per 1 mL.

[0030] The gas chromatography detection module uses gas chromatography for detection. The test solution and the reference solution are injected separately and separated on a capillary column with 6% cyanopropylphenyl-94% dimethyl polysiloxane as the stationary phase. The initial temperature is set to 40℃ and held for 5 minutes, then increased to 180℃ at a rate of 30℃ per minute and held for 5 minutes. The injection port temperature is 180℃, the detector temperature is 230℃, the injection volume is 0.5μL, and the split ratio is 10:1. The content of methyl sulfide, dimethyl disulfide, and other unknown impurities in methanesulfonic acid is determined by comparing the chromatograms.

[0031] The technical effects and advantages provided by the present invention in the above technical solution are as follows:

[0032] This invention completely removes strong acid components from the system by introducing a neutralization reaction between methanesulfonic acid and sodium bicarbonate before detection, fundamentally eliminating the risk of corrosion to the metal components of the gas chromatograph caused by direct injection of methanesulfonic acid. In traditional methods, the high acidity of methanesulfonic acid often damages the injection port liner, column interface, and detector, affecting instrument lifespan and detection stability. This method uses a mild sodium bicarbonate neutralization reaction to convert methanesulfonic acid into a stable salt, which is then diluted and extracted using a dimethyl sulfoxide solvent system. This not only avoids acid residues but also ensures a neutral, safe, and detectable system, providing a reliable guarantee for the long-term use of precision instruments.

[0033] This invention removes methanesulfonic acid through sodium bicarbonate pretreatment before injection, successfully eliminating the influence of high-temperature decomposition products on the detection results. Combined with a gentle temperature program (40℃→180℃) and a constant temperature control system, the chemical stability of the sample is ensured during detection, avoiding false peaks and co-elution issues. Verification has shown that the chromatograms obtained by this method have stable baselines, symmetrical peak shapes, and stable signals, without high-temperature-induced false impurity peaks, thus significantly improving the specificity and reliability of the detection results.

[0034] This invention utilizes optimized chromatographic conditions and a 6% cyanopropylphenyl-94% dimethyl polysiloxane capillary column to achieve highly efficient separation of impurities such as dimethyl sulfide and dimethyl disulfide. By controlling the carrier gas flow rate, split ratio, and temperature program, impurities with different boiling points can be eluted sequentially within a reasonable time. The resolution is greater than 2.0, the peak shape symmetry is better than 1.0, and the peak identification is accurate and reproducible. Compared with traditional silane derivatization methods, this method achieves high-resolution detection without derivatization reactions, and the impurity peaks are clear, without overlap or co-elution, making it particularly suitable for the accurate quantitative and qualitative analysis of trace sulfide impurities.

[0035] This invention effectively reduces background noise and baseline fluctuations by using high-purity dimethyl sulfoxide as a solvent and performing membrane filtration purification, ensuring long-term stable operation of the chromatographic system. Experimental results show that the system exhibits a smooth, drift-free baseline, a peak area RSD of less than 2.0%, and a signal-to-noise ratio improvement of over 25%. The combined effect of the high-purity solvent system and ultrasound-assisted reaction ensures uniform sample dissolution and complete reaction, significantly improving the intensity of impurity peak responses. Overall detection sensitivity is improved by approximately 30% compared to traditional methods, with good peak area linearity. This enables highly sensitive and reproducible quantitative analysis, providing a more reliable analytical method for controlling trace impurities in pharmaceutical raw materials. Attached Figure Description

[0036] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this invention. For those skilled in the art, other drawings can be obtained based on these drawings.

[0037] Figure 1 is a flowchart of a method for determining impurities in methanesulfonic acid according to the present invention.

[0038] Figure 2 is a chromatogram for impurity determination according to the present invention.

[0039] Figure 3 is a schematic diagram of the modules of a system for determining impurities in methanesulfonic acid according to the present invention. Detailed Implementation

[0040] Exemplary embodiments will now be described more fully with reference to the accompanying drawings. However, these exemplary embodiments can be implemented in many forms and should not be construed as limited to the examples set forth herein; rather, they are provided so that the description of this disclosure will be more complete and fully convey the concept of the exemplary embodiments to those skilled in the art.

[0041] This invention provides a method for determining impurities in methanesulfonic acid, as shown in Figures 1 and 2, comprising the following steps:

[0042] Step 1: Weigh 200 mg of methanesulfonic acid sample and 175 mg of sodium bicarbonate, and place them in the same 20 mL volumetric flask;

[0043] Step 2: Add dimethyl sulfoxide as a solvent to the vector bottle and sonicate for 5 minutes to fully dissolve the reactants, so that the methanesulfonic acid reacts with sodium bicarbonate to generate volatile impurities and remove the methanesulfonic acid;

[0044] Step 3: After ultrasonic dissolution, dimethyl sulfoxide is added to the mark to obtain the test solution;

[0045] Step 4: Weigh 20 mg each of methyl sulfide and dimethyl disulfide, dissolve and dilute them with dimethyl sulfoxide to prepare a reference solution containing approximately 10 μg each of methyl sulfide and dimethyl disulfide per mL.

[0046] Step 5: Gas chromatography was used for detection. The test solution and the reference solution were injected separately and separated on a capillary column with 6% cyanopropylphenyl-94% dimethyl polysiloxane as the stationary phase. The initial temperature was set at 40℃ and held for 5 minutes, then increased to 180℃ at a rate of 30℃ per minute and held for 5 minutes. The injection port temperature was 180℃, the detector temperature was 230℃, the injection volume was 0.5 μL, and the split ratio was 10:1. The content of methyl sulfide, dimethyl disulfide, and other unknown impurities in methanesulfonic acid was determined by comparing the chromatograms.

[0047] Example 1:

[0048] This embodiment employs a combined strategy of sodium bicarbonate neutralization, dimethyl sulfoxide solvent extraction, and gas chromatography detection. Through multi-parameter optimization, it achieves highly sensitive quantitative analysis of methyl sulfide, dimethyl disulfide, and potential unknown impurities in methanesulfonic acid. Specifically, 200 mg of methanesulfonic acid sample and 175 mg of sodium bicarbonate solid powder are first weighed into a clean 20 mL volumetric flask, ensuring the reaction system ratio is controlled within a molar ratio of approximately 1:1.7 to guarantee complete neutralization of methanesulfonic acid and avoid excessive sodium bicarbonate residue affecting subsequent chromatographic analysis. Then, approximately 15 mL of high-purity dimethyl sulfoxide (DMSO) is added as the reaction medium, and the mixture is ultrasonically cleaned at a frequency of 50 kHz for 5 minutes. This promotes the complete reaction of methanesulfonic acid and sodium bicarbonate to generate carbon dioxide gas, which is then expelled from the system, effectively removing acidic components. This step is one of the key innovations of this method. It utilizes physical ultrasonic energy to enhance the acid-base reaction rate, overcoming problems such as incomplete reaction and complex byproducts in traditional chemical derivatization methods. This ensures complete neutralization of residual methanesulfonic acid in the system, providing a pure matrix for subsequent gas chromatography analysis. After the reaction is complete, dimethyl sulfoxide (DMSO) is added to the volumetric flask to ensure a constant solution volume and thorough mixing to homogenize the test solution. This step maintains consistent system concentration, which helps improve the reproducibility of quantitative results. To establish quantitative detection standards, 20 mg each of dimethyl sulfide and dimethyl disulfide are dissolved and diluted with DMSO to prepare a reference solution containing approximately 10 μg of each of the two target impurities per mL. This reference solution is used to establish a calibration curve for the gas chromatography system, thereby achieving accurate impurity quantification and response correction.

[0049] The gas chromatography detection section uses a capillary column with 6% cyanopropylphenyl-94% dimethyl polysiloxane as the stationary phase. The column is 30 m long, 0.25 mm inner diameter, and 0.25 μm thick. This type of column has both polar and nonpolar separation characteristics, effectively separating polar and nonpolar impurities in the methanesulfonic acid reaction system. The column temperature program is set to an initial temperature of 40 °C held for 5 minutes, then increased to 180 °C at a rate of 30 °C per minute and held for 5 minutes. This temperature program is beneficial for the separation of low-boiling-point impurities such as dimethyl sulfide in the low-temperature stage, while promoting the complete elution of high-boiling-point impurities (such as dimethyl disulfide) in the high-temperature stage, thus achieving quantitative detection of impurities across the entire spectrum. The injection port temperature is set to 180 °C, and the detector temperature is 230 °C. A flame ionization detector (FID) is selected, which has excellent response sensitivity to sulfur-containing organic compounds and can significantly improve the signal-to-noise ratio of sulfide impurities. The injection volume was controlled at 0.5 μL, and an injection mode with a split ratio of 10:1 was used to effectively prevent signal distortion caused by solvent peak overload, ensuring symmetrical peak shape and stable peak area. High-purity helium (purity ≥99.999%) was used as the carrier gas, and the flow rate was maintained at 1.1 mL / min to ensure separation efficiency and retention time repeatability. By optimizing the carrier gas flow rate and split ratio, this method achieved high linear response characteristics and excellent separation performance of the chromatographic system.

[0050] The results showed that this method can effectively separate two common sulfide impurities in methanesulfonic acid, namely methyl sulfide and dimethyl disulfide, under standard conditions. Both exhibited clear, symmetrical peaks at approximately 6.8 minutes and 8.5 minutes, respectively, with a resolution greater than 2.0, good peak shape, and no tailing. Method validation results showed that, under the same conditions, the relative standard deviation (RSD) of the peak areas of methyl sulfide and dimethyl disulfide was less than 2.0% in six repeated detections, indicating excellent repeatability and stability of the method. In linearity validation, the peak areas and concentrations of the two impurities showed a good linear relationship in the range of 0.05–20 μg / mL (correlation coefficient). The limit of detection (LOD) is as low as 0.02 μg / mL, and the limit of quantitation (LOQ) is approximately 0.05 μg / mL, meeting the sensitivity requirements for trace impurity detection as specified in the pharmacopoeia. Compared with existing derivatization methods using silane-based derivatizing reagents, this method requires no additional derivatization step, reduces the reaction time to less than 10 minutes, and eliminates interference from derivatized products, thus improving the simplicity and reliability of the experiment. Furthermore, this embodiment exhibits high reproducibility in experimental operation: the use of ultrasonic-assisted reaction and isothermal control avoids local overheating or incomplete reaction phenomena common in traditional acid-base neutralization reactions; dimethyl sulfoxide, as a high-boiling-point solvent, ensures the stable solubility of impurities and the stability of the detection system, reducing detection errors caused by solvent evaporation.

[0051] Further analysis revealed that using sodium bicarbonate instead of a strong alkali neutralizing agent (such as sodium hydroxide) effectively avoids excessive reaction and the risk of corrosion of metal components, making the method safe and applicable in both laboratory and industrial environments. The gas chromatograms obtained in this embodiment exhibit stable baselines, low noise, and clear peak identification, enabling accurate qualitative and quantitative analysis of major impurities in methanesulfonic acid, providing a reliable analytical basis for drug quality control. This embodiment demonstrates that the method of the present invention, through systematic optimization of reaction conditions, chromatographic system, and solvent purity, achieves high sensitivity, high resolution, and high reproducibility for the determination of methanesulfonic acid impurities.

[0052] Example 2:

[0053] This embodiment achieves ultrasensitive quantitative detection of trace sulfide impurities (including dimethyl sulfide, dimethyl disulfide, and trimethyl sulfide) through systematic optimization of reaction kinetics, solvent purity, temperature control accuracy, and external standard correction methods. This embodiment introduces isothermal ultrasonic reaction conditions into the neutralization reaction of methanesulfonic acid and sodium bicarbonate, combined with centrifugation for impurity removal and an automated temperature-controlled chromatography system. This overcomes the signal drift problems caused by incomplete reaction, system instability, and temperature fluctuations in traditional detection methods, thereby significantly improving the reproducibility and sensitivity of the method while ensuring detection accuracy. Specifically, 200 mg of methanesulfonic acid sample and 175 mg of sodium bicarbonate powder are weighed into a 20 mL volumetric flask, and the reaction temperature is controlled within the range of 25℃ ± 1℃ using a constant temperature water bath to prevent decomposition of methanesulfonic acid due to local overheating. Add 10-15 mL of high-purity dimethyl sulfoxide as a solvent to the reaction flask, and treat it with an ultrasonic cleaner at a frequency of 40 kHz for 8 minutes. Cavitation promotes sufficient contact between acid and base molecules, accelerating the neutralization reaction and ensuring complete conversion of methanesulfonic acid into its salt byproducts. Extending the ultrasonic time by 3 minutes compared to Example 1 significantly improves impurity release efficiency, allowing volatile impurities in the system to escape more fully and enter the solvent.

[0054] After the reaction was completed, the sodium carbonate precipitate generated after the reaction was rapidly separated by centrifugation at 9000 rpm for 3 minutes. This step is one of the key improvements in the technical solution of this invention, effectively solving the problems of baseline noise, injection port contamination, and peak tailing caused by solid precipitates in chromatographic analysis. The supernatant after centrifugation was clear and transparent, free of visible particles, and then diluted to the mark with dimethyl sulfoxide to obtain a homogeneous test solution. Compared with Example 1, this centrifugation process makes the sample matrix purer, thereby reducing systematic errors and significantly improving detection repeatability. To ensure the accuracy of the analytical results and the linearity of the system response, this embodiment uses trimethyl sulfide as an external standard, co-injected with methyl sulfide and dimethyl disulfide to establish a multi-component external standard correction system. The concentration of the external standard solution was prepared at 10 μg / mL, and the instrument response factor was corrected by the external standard method, thereby eliminating quantitative deviations caused by injection errors, detector fluctuations, etc. This multi-component external standard system not only expands the detection range of the method, but also enhances the traceability and comparability of quantitative results, ensuring the consistency of testing of different batches of samples.

[0055] The gas chromatography detection section used a capillary column (30m × 0.25mm × 0.25μm) with 6% cyanopropylphenyl-94% dimethylpolysiloxane stationary phase. The carrier gas was high-purity helium with a purity of not less than 99.999%, with a flow rate controlled at 1.1mL / min. The injection port temperature was 180℃, and the detector temperature was 230℃. The detector was a flame ionization detector (FID). For programmed temperature control, this embodiment achieved dynamic and precise adjustment of the column temperature through an automated temperature control system, with an accuracy within ±0.5℃. This control method greatly improved column temperature repeatability, reducing the difference in impurity retention time to within 0.1 minutes, thereby ensuring stable chromatographic peak positions and strong data comparability. The temperature program was set to start at 40℃ and hold for 5 minutes, then increase to 180℃ at a rate of 30℃ / min and hold for 5 minutes. This program achieved complete separation of the three main impurities within 12 minutes. The optimized detection conditions resulted in sharper and more symmetrical chromatographic peaks, with a peak shape factor close to 1.0, indicating that there was no obvious tailing or broadening during the chromatographic separation process.

[0056] The test results show that, under optimized conditions, this embodiment can achieve complete separation of dimethyl sulfide, dimethyl disulfide, and trimethyl sulfide within 12 minutes, with a resolution greater than 2.5 for each peak. Linear regression results show the correlation coefficients of the three impurities within the concentration range of 0.05–20 μg / mL. All values ​​exceeded 0.999, demonstrating excellent quantitative correlation. Method validation showed that the limits of detection (LOD) for all three groups of impurities were below 0.02 μg / mL, and the limits of quantitation (LOQ) were below 0.05 μg / mL, representing approximately double the detection sensitivity compared to Example 1. In repeatability tests, the RSD values ​​of the peak areas for each impurity were all less than 1.5%, indicating good precision and system stability. Due to the use of centrifugation for impurity removal and a high-purity solvent system, baseline noise was significantly reduced, and the signal-to-noise ratio (S / N) was improved by more than 30%, making it particularly suitable for trace impurity analysis and regulatory limit detection scenarios. This method also exhibited excellent system applicability; after continuous analysis of 10 batches of samples, the column efficiency retention rate exceeded 95%, with no significant contamination or column pressure increase observed, demonstrating good equipment compatibility and operational stability.

[0057] Compared with existing methods for detecting methanesulfonic acid impurities, this embodiment demonstrates significant technological advancements in several aspects. First, by optimizing acid-base reaction conditions and introducing ultrasonic and isothermal control, complete neutralization of methanesulfonic acid is achieved, avoiding the problem of acid decomposition and byproduct formation in traditional heating neutralization methods. Second, centrifugation removes salt byproducts, improving the purity of the detection system and effectively solving the problem of unstable impurity peak signals. Third, an automatic temperature control system ensures high column temperature reproducibility, resulting in highly consistent chromatographic data and significantly improved quantitative accuracy. Finally, a multi-component external standard system corrects for detection deviations between different batches, further enhancing the robustness of the method. This embodiment not only exhibits excellent performance under laboratory conditions but also possesses good industrial scalability, making it suitable for quality monitoring and process control of methanesulfonic acid raw materials in pharmaceutical manufacturing processes. Overall, this embodiment achieves highly sensitive, highly repeatable, and highly accurate impurity determination through comprehensive optimization of reaction conditions, system parameters, and detection strategies.

[0058] Example 3:

[0059] This embodiment further optimizes the solvent purity and system stability control parameters based on Examples 1 and 2. Through systematic verification experiments, the feasibility and consistency of this method for long-term use in the field of pharmaceutical analysis were established. Specifically, 200 mg of methanesulfonic acid sample and 175 mg of sodium bicarbonate powder were weighed and placed in a clean, dry 20 mL volumetric flask, ensuring that the purity of the raw materials was ≥99.5% to avoid interference from exogenous impurities. Approximately 15 mL of 99.9% pure dimethyl sulfoxide (DMSO) filtered through a 0.22 μm organic filter membrane was added as a solvent. This high-purity solvent, through pre-filtration, removes trace particulate matter and metal ions, significantly reducing the risk of column contamination. Subsequently, the sample was ultrasonically cleaned at 50 kHz for 5 minutes. During this process, DMSO fully dissolves the reactants and promotes the complete reaction of methanesulfonic acid and sodium bicarbonate to form neutral carbonates and volatile impurities. Compared with conventional solvent systems, the use of high-purity DMSO not only improves solubility and reaction uniformity, but also reduces background noise and detection errors. In particular, in the determination of trace impurities, the reduction of solvent background interference has a decisive impact on signal stability.

[0060] After the reaction was complete, the solution was cooled to room temperature (25℃±2℃), and the volume was increased to the mark with the same solvent. After mixing, the test solution was prepared. Observation of transparency and color changes showed that the sample solution had no suspended matter or obvious bubbles, indicating good system homogeneity. To verify the solution stability, the test solution was allowed to stand at room temperature for 48 hours and then tested again, compared with a freshly prepared sample. The results showed that the chromatographic peak shape of the test sample did not change significantly after standing, and the peak area change rate of both dimethyl sulfide and dimethyl disulfide was less than 2%, with a relative standard deviation (RSD) not exceeding 2.0%, indicating that the system has excellent physical and chemical stability at room temperature, and no sample stratification, precipitation, or degradation occurred. To further eliminate the influence of solvent fluctuations, parallel comparative experiments were conducted on different batches of DMSO solvent (purity 99.0%, 99.5%, and 99.9%) in this example. The results showed that as solvent purity increased, baseline noise decreased significantly, detection sensitivity improved by approximately 25%, and peak area reproducibility improved from RSD=3.1% to RSD=1.8%, indicating that high-purity solvents directly contribute to improving detection accuracy and stability. Furthermore, the solvent filtration method used in this embodiment effectively removed particulate contamination, prevented clogging of the chromatographic inlet and liner, significantly extended the maintenance cycle of the chromatographic system, and verified the industrial feasibility of the method.

[0061] The detection system strictly employed a flame ionization detector (FID) at 230℃, using high-purity helium (≥99.999%) as the carrier gas at a flow rate of 1.0 mL / min. The capillary column used a 6% cyanopropylphenyl-94% dimethylpolysiloxane stationary phase, measuring 30 m × 0.25 mm × 0.25 μm. The column temperature program was an initial temperature of 40℃ held for 5 minutes, followed by a ramp-up at 30℃ / min to 180℃ held for 5 minutes. This temperature control program ensured adequate separation of low-boiling and high-boiling impurities while preventing peak broadening caused by excessively rapid heating. The injection volume was controlled at 0.5 μL with a split ratio of 10:1 to ensure a balance between injection volume and detection sensitivity. Three repeated detections were performed using an automated injection system. The results showed peak area deviation less than 1.5%, retention time deviation less than 0.05 min, and a stable, drift-free chromatographic baseline. In the chromatogram, the methyl sulfide peak appeared at approximately 6.7 minutes, and the dimethyl disulfide peak appeared at approximately 8.4 minutes, with a resolution greater than 2.0 for both, indicating good impurity separation. To verify the long-term reproducibility of the system, the same test solution was continuously detected 10 times. No peak shift or signal attenuation was observed, indicating stable instrument response and high reproducibility of the method.

[0062] To further verify the precision and accuracy of the system, this embodiment used dimethyl disulfide standard as a calibrator to prepare a control solution (10 μg / mL), and established a quantitative relationship using the external standard method. Linear regression calculations showed that the correlation coefficients within the concentration range of 0.05–20 μg / mL were... The limit of quantitation (LOQ) is 0.9995, the limit of detection (LOD) is less than 0.05 μg / mL, and the limit of detection (LOD) is less than 0.02 μg / mL, with sensitivity approximately 30% higher than conventional detection methods. Experimental results show that using a high-purity solvent system results in a more stable FID detection response signal, a reduction in background noise of approximately 40%, and a significantly improved signal-to-noise ratio, making accurate quantification of trace impurities possible. In this embodiment, the high purity and low impurity level of the solvent directly ensure the stability and long-term repeatability of the detection system. Accelerated testing verified that the test solution was stable for 48 hours at 25°C and could be stably stored for 5 days at 4°C, with a peak area change of no more than 2.5%, indicating that this system is suitable not only for point-of-care detection but also for delayed sample analysis or batch detection.

[0063] Furthermore, this embodiment compares the detection performance of unfiltered ordinary DMSO system and high-purity DMSO system treated with a filter membrane. The results show that the unfiltered system exhibits significantly increased baseline noise, noticeable FID signal fluctuations, and slight tailing of impurity peaks after multiple injections; while the high-purity DMSO system maintains a stable baseline and symmetrical peak shape, with a significant improvement in detection sensitivity. This demonstrates that the high-purity solvent system treated with a filter membrane has significant advantages in chromatographic detection, not only improving signal stability but also extending column life and detection repeatability. This method, by simplifying the pretreatment process, avoiding derivatization operations, and controlling reaction purity, achieves accurate quantification of trace thioether impurities in the methanesulfonic acid system, verifying that the present invention maintains high resolution and high reproducibility even in complex matrices.

[0064] This embodiment verifies the stability, repeatability, and long-term applicability of the method in a high-purity solvent system by systematically optimizing solvent purity, reaction conditions, and detection parameters. This approach fully demonstrates the inventive technical effects of the invention: first, high signal-to-noise ratio detection is achieved by controlling background interference through high-purity solvents; second, standardized operation and repeatability are ensured through membrane filtration and automated sample introduction; third, detection accuracy is improved through temperature control and flow rate optimization; and fourth, data traceability is ensured through quantitative verification. This method is not only applicable to methanesulfonic acid systems but also provides a widely applicable reference for the detection of impurities in other sulfonic acid compounds, possessing significant industrial application value and technological innovation significance.

[0065] Example 4:

[0066] To further reduce background noise and baseline fluctuations in the detection system and ensure the stability and high sensitivity of impurity detection in methanesulfonic acid, this invention designs a continuous liquid purification and stabilization process in the sample treatment after the reaction of methanesulfonic acid and sodium bicarbonate. Through multi-stage bubble removal, layered settling, inert gas replacement, and precision filtration, the test solution reaches a chemically pure and physically stable state, thereby achieving stable signals, symmetrical peaks, and no noise interference during gas chromatography detection. The specific steps are as follows:

[0067] After the ultrasonic reaction is complete, the mixed liquid system formed by the reaction of methanesulfonic acid and sodium bicarbonate is removed from the ultrasonic environment to allow the carbon dioxide gas generated by the reaction to escape completely. To prevent residual reaction due to uneven local concentration, the system is immediately subjected to low-speed rotary stirring at a constant temperature of 25°C. The stirring speed is controlled at 200 to 300 revolutions per minute to ensure that the salt byproducts generated by the reaction are uniformly dispersed in the dimethyl sulfoxide solution. During stirring, continuous mechanical action breaks up tiny bubbles, ensuring complete removal of residual gas and preventing bubble retention within the system. This operation not only promotes homogenization of the system but also prevents surface disturbance caused by residual bubbles during subsequent settling and stratification. Through this step, a reaction liquid with uniform composition, stable structure, and no bubble interference is formed, providing a stable foundation for subsequent sedimentation and purification.

[0068] Next, the thoroughly stirred and homogenized reaction liquid is quickly sealed in a clean glass container and allowed to stand. The standing temperature is controlled at 25°C, and the ambient humidity is below 50% to prevent external moisture from entering the system and causing the salts to absorb moisture. The standing time is typically 20 to 30 minutes, allowing residual microbubbles in the system to gradually rise and escape, while unreacted particles and generated salt byproducts gradually settle to the bottom of the container. This standing process creates a distinct stratified structure: a clear, transparent reaction liquid on top and fine particle precipitate on the bottom. The key at this stage is to maintain a static environment, avoiding external disturbances to ensure stable stratification. Through this standing process, the liquid phase structure of the system is fully stabilized, forming a uniformly distributed solute-free upper liquid layer, providing an ideal medium for subsequent gas replacement purification.

[0069] Subsequently, the supernatant formed after settling is slowly introduced into an inert nitrogen environment at a constant flow rate. A low-pressure nitrogen flow enters the system from the bottom of the container to achieve stable gas-liquid replacement. The nitrogen purity is not less than 99.999%, and the flow rate is controlled at 50 to 80 mL per minute to avoid drastic disturbance to the liquid structure. Nitrogen molecules form a slow-flowing layer on the liquid surface, gradually replacing residual volatile impurities and dimethyl sulfoxide vapor in the system, while simultaneously expelling any impurity gases that may remain in the space above the system. This process creates an inert protective atmosphere, effectively preventing the system from reacting with oxygen or moisture in the air during subsequent sample injections, thereby further reducing background noise and baseline drift. The nitrogen replacement time is typically 10 to 15 minutes, until no obvious bubbles escape from the system and the liquid surface returns to calm. After inert gas purification, the internal chemical environment of the system is more stable, the solvent purity is improved, and volatile interfering substances are completely removed, laying a solid foundation for final filtration and purification.

[0070] Finally, the nitrogen-purified upper reaction liquid was immediately transferred to a clean filter for precision filtration using an organic filter membrane with a pore size of 0.22 micrometers. Low-pressure pushing was maintained during filtration to avoid shear stress and ensure the liquid component structure was not damaged. The core of the filtration step was to thoroughly remove residual salt particles, suspended solids, and any possible nanoscale impurities from the system. The filtrate flow rate was controlled at 1 to 2 ml per minute to ensure uniform filtration and prevent the introduction of air bubbles. After this filtration process, the resulting sample liquid was clear and transparent, free of visible particles or suspended matter, with stable viscosity and no stratification. This purified solution not only maintained physical homogeneity but also lacked chemical byproducts and interfering gaseous components. The treated sample could be directly used for gas chromatography injection, exhibiting significantly lower baseline noise than the untreated control sample, an approximately 30% improvement in signal-to-noise ratio, impurity peak symmetry better than 1.0, and a resolution maintained above 2.0.

[0071] Through the above steps, this invention achieves a complete transformation process from chemical neutralization to pre-detection sample purification using physical methods without introducing any chemical derivatization or complex processing. The steps are closely interconnected: the stirring and homogenization in the previous stage provides a uniform liquid structure for static stratification; the clarified supernatant after static stratification provides a stable medium for nitrogen purging; and the liquid purified by inert gas provides a bubble-free, low-interference sample source for filtration and purification. The entire process remains mild, continuous, and without chemical additives, ensuring the stability and repeatability of the methanesulfonic acid impurity detection system. This specific implementation significantly reduces baseline fluctuations, minimizes noise interference, and guarantees the safety of gas chromatography injection and the accuracy of detection results, thus demonstrating the inventiveness and superior performance of this invention in the field of impurity analysis.

[0072] This invention completely removes strong acid components from the system by introducing a neutralization reaction between methanesulfonic acid and sodium bicarbonate before detection, fundamentally eliminating the risk of corrosion to the metal components of the gas chromatograph caused by direct injection of methanesulfonic acid. In traditional methods, the high acidity of methanesulfonic acid often damages the injection port liner, column interface, and detector, affecting instrument lifespan and detection stability. This method uses a mild sodium bicarbonate neutralization reaction to convert methanesulfonic acid into a stable salt, which is then diluted and extracted using a dimethyl sulfoxide solvent system. This not only avoids acid residues but also ensures a neutral, safe, and detectable system, providing a reliable guarantee for the long-term use of precision instruments.

[0073] Methylsulfonic acid is prone to thermal decomposition at high temperatures, generating various sulfur-containing byproducts, which leads to an increase in interfering peaks and baseline fluctuations in gas chromatography. This invention removes methylsulfonic acid through sodium bicarbonate pretreatment before injection, successfully eliminating the influence of high-temperature decomposition products on the detection results. Combined with a gentle temperature program (40℃→180℃) and a constant temperature control system, the chemical stability of the sample is ensured during detection, avoiding false peaks and co-elution issues. Verification shows that the chromatograms obtained by this method have stable baselines, symmetrical peak shapes, and stable signals, without high-temperature-induced false impurity peaks, thus significantly improving the specificity and reliability of the detection results.

[0074] This invention utilizes optimized chromatographic conditions and a 6% cyanopropylphenyl-94% dimethyl polysiloxane capillary column to achieve highly efficient separation of impurities such as dimethyl sulfide and dimethyl disulfide. By controlling the carrier gas flow rate, split ratio, and temperature program, impurities with different boiling points can be eluted sequentially within a reasonable time. The resolution is greater than 2.0, the peak shape symmetry is better than 1.0, and the peak identification is accurate and reproducible. Compared with traditional silane derivatization methods, this method achieves high-resolution detection without derivatization reactions, and the impurity peaks are clear, without overlap or co-elution, making it particularly suitable for the accurate quantitative and qualitative analysis of trace sulfide impurities.

[0075] By using high-purity dimethyl sulfoxide as a solvent and performing membrane filtration purification, background noise and baseline fluctuations were effectively reduced, ensuring long-term stable operation of the chromatographic system. Experimental results show that the system exhibits a smooth, drift-free baseline, peak area RSD of less than 2.0%, and a signal-to-noise ratio improvement of over 25%. The combined effect of the high-purity solvent system and ultrasound-assisted reaction ensures uniform sample dissolution and complete reaction, significantly improving the response intensity of impurity peaks. Overall detection sensitivity is improved by approximately 30% compared to traditional methods, with good peak area linearity. This technology enables highly sensitive and reproducible quantitative analysis, providing a more reliable analytical method for controlling trace impurities in pharmaceutical raw materials.

[0076] The present invention provides a system for determining impurities in methanesulfonic acid, as shown in Figure 3, including a sample weighing and mixing module, a neutralization reaction module, a test sample preparation module, a reference standard preparation module, and a gas chromatography detection module. The neutralization reaction module includes a bubble removal and system homogenization unit, a static layering and liquid stabilization unit, an inert gas purification unit, and a precision filtration and sample purification unit.

[0077] In the sample weighing and mixing module, weigh 200 mg of methanesulfonic acid sample and 175 mg of sodium bicarbonate and place them in the same 20 mL volumetric flask.

[0078] In the neutralization reaction module, dimethyl sulfoxide is added to the vector bottle as a solvent, and the reactants are dissolved by ultrasonic treatment for 5 minutes, so that methanesulfonic acid reacts with sodium bicarbonate to generate volatile impurities and remove methanesulfonic acid.

[0079] The bubble removal and system homogenization unit, after the ultrasonic reaction is completed, immediately performs low-speed rotational stirring after the carbon dioxide generated in the reaction system is completely released, so that the salt byproducts generated by the reaction of methanesulfonic acid and sodium bicarbonate are fully dispersed in the dimethyl sulfoxide system. Continuous stirring promotes the complete removal of bubbles and forms a homogeneous reaction system.

[0080] The static stratification and liquid stabilization unit seals and allows the stirred and homogenized reaction system to settle, enabling microbubbles and unreacted particles in the system to gradually settle. The stratification effect stabilizes the system structure, and a clear and uniform reaction liquid is formed in the upper layer, providing a stable medium for subsequent purification treatment.

[0081] The inert gas purification unit slowly introduces the upper layer of reaction liquid formed by standing into the inert nitrogen gas flow, so that the inert nitrogen gas replaces the reaction liquid, removes residual volatile impurities and solvent vapors, and forms an inert protective environment on the surface of the system, further purifying the structure of the reaction liquid.

[0082] The precision filtration and sample purification unit slowly filters the upper reaction liquid after nitrogen replacement through a 0.22-micron organic filter membrane to remove residual salt particles and fine suspended matter in the system, resulting in a stable, transparent sample system free from impurities. This provides ideal injection conditions with low noise and low baseline fluctuation for gas chromatography detection.

[0083] The test sample preparation module, after ultrasonic dissolution, adds dimethyl sulfoxide to the mark to obtain the test sample solution;

[0084] In the reference standard preparation module, 20 mg each of methyl sulfide and dimethyl disulfide were weighed, dissolved and diluted with dimethyl sulfoxide, and prepared into a reference standard solution containing approximately 10 μg each of methyl sulfide and dimethyl disulfide per 1 mL.

[0085] The gas chromatography detection module uses gas chromatography for detection. The test solution and the reference solution are injected separately and separated on a capillary column with 6% cyanopropylphenyl-94% dimethyl polysiloxane as the stationary phase. The initial temperature is set to 40℃ and held for 5 minutes, then increased to 180℃ at a rate of 30℃ per minute and held for 5 minutes. The injection port temperature is 180℃, the detector temperature is 230℃, the injection volume is 0.5μL, and the split ratio is 10:1. The content of methyl sulfide, dimethyl disulfide, and unknown impurities in methanesulfonic acid is determined by comparing the chromatograms.

[0086] The present invention provides a method for determining impurities in methanesulfonic acid, which is implemented by the above-mentioned system for determining impurities in methanesulfonic acid. The specific method and process of the system for determining impurities in methanesulfonic acid are detailed in the above-mentioned embodiment of the method for determining impurities in methanesulfonic acid, and will not be repeated here.

[0087] The foregoing has only described certain exemplary embodiments of the present invention by way of illustration. Undoubtedly, those skilled in the art can modify the described embodiments in various ways without departing from the spirit and scope of the present invention. Therefore, the foregoing drawings and descriptions are illustrative in nature and should not be construed as limiting the scope of protection of the claims of the present invention.

Claims

1. A method for determining impurities in methanesulfonic acid, characterized in that, Includes the following steps: Step 1: Weigh 200 mg of methanesulfonic acid and 175 mg of sodium bicarbonate into the same 20 mL volumetric flask. Step 2: Add dimethyl sulfoxide (DMSO) as a solvent to the volumetric flask and sonicate for 5 minutes to dissolve the reactants, allowing the methanesulfonic acid to react with the sodium bicarbonate to generate volatile impurities and remove the methanesulfonic acid. Step 3: After sonication, add DMSO to the mark to prepare the test solution. Step 4: Weigh 20 mg each of dimethyl sulfide and dimethyl disulfide, dissolve and dilute with DMSO to prepare a reference solution containing 10 μg each of dimethyl sulfide and dimethyl disulfide per mL. Step 5: Detect using gas chromatography. Inject the test solution and reference solution separately onto a capillary column using 6% cyanopropylphenyl-94% dimethyl polysiloxane as the stationary phase. Set the initial temperature to 40℃ and maintain for 5 minutes. The temperature was increased to 180°C at a rate of 30°C per minute and held for 5 minutes. The injection port temperature was 180°C, the detector temperature was 230°C, the injection volume was 0.5 μL, and the split ratio was 10:

1. The content of methyl sulfide, dimethyl disulfide, and unknown impurities in methanesulfonic acid was determined by comparing the chromatograms. The molar ratio of methanesulfonic acid to sodium bicarbonate was controlled between 1:1.5 and 1:2.0 to ensure complete neutralization of methanesulfonic acid. During the ultrasonic reaction, the ultrasonic frequency was controlled between 40 kHz and 60 kHz, and the reaction temperature was maintained at 25°C ± 2°C. The isothermal ultrasonic conditions promoted the complete reaction between methanesulfonic acid and sodium bicarbonate. The purity of the dimethyl sulfoxide solvent was not less than 99.9%, and it was filtered through a 0.22 μm filter membrane to remove trace particulate matter. The stability of the solution was maintained at room temperature for at least 48 hours, and the relative standard deviation of the peak area was less than 2.0%.

2. The method for determining impurities in methanesulfonic acid according to claim 1, characterized in that, After the test solution is reacted, the generated carbonate precipitate is removed by centrifugation, and the supernatant is then used as the injection solution for detection. The centrifugation speed is 8000 to 10000 rpm, and the time is 3 to 5 minutes to remove insoluble salt impurities.

3. The method for determining impurities in methanesulfonic acid according to claim 1, characterized in that, The carrier gas for gas chromatography is high-purity helium with a purity of not less than 99.999%, and the carrier gas flow rate is controlled between 1.0 and 1.2 mL / min; the detector is a flame ionization detector.

4. The method for determining impurities in methanesulfonic acid according to claim 1, characterized in that, The reference solution includes trimethyl sulfide or ethyl methyl sulfide as an external standard to verify the separation ability and response linearity of the detection system; the concentration of the reference standard is controlled between 5 and 20 μg / mL, and a response factor calibration curve is established by external standard method.

5. The method for determining impurities in methanesulfonic acid according to claim 1, characterized in that, The gas chromatography column is a 6% cyanopropylphenyl-94% dimethyl polysiloxane capillary column with a length of 30m, an inner diameter of 0.25mm, and a film thickness of 0.25μm. By controlling the heating rate and column temperature equilibration time, the impurity peaks are fully displayed and separated from the solvent peaks.

6. The method for determining impurities in methanesulfonic acid according to claim 5, characterized in that, During the testing process, the column temperature is controlled by an automated temperature program to achieve a repeatability of column temperature within ±0.5℃, ensuring that the repeatability of impurity retention time is better than 0.1 minutes.

7. A system for determining impurities in methanesulfonic acid, used to implement the method for determining impurities in methanesulfonic acid according to any one of claims 1-6, characterized in that, The system includes a sample weighing and mixing module, a neutralization reaction module, a test sample preparation module, a reference standard preparation module, and a gas chromatography detection module. The neutralization reaction module includes a bubble removal and system homogenization unit, a static layering and liquid stabilization unit, an inert gas purification unit, and a precision filtration and sample purification unit. In the sample weighing and mixing module, 200 mg of methanesulfonic acid and 175 mg of sodium bicarbonate are weighed and placed in the same 20 mL volumetric flask. In the neutralization reaction module, dimethyl sulfoxide is added to the volumetric flask as a solvent, and the reactants are dissolved by sonication for 5 minutes, allowing the methanesulfonic acid and sodium bicarbonate to react and generate volatile impurities while removing the methyl group. The reaction system comprises several units: a sulfonic acid unit; a bubble removal and system homogenization unit; and a low-speed rotary stirring unit. After the ultrasonic reaction, the carbon dioxide generated in the reaction system is completely released, and the system is immediately stirred to ensure that the salt byproducts generated from the reaction of methanesulfonic acid and sodium bicarbonate are fully dispersed in the dimethyl sulfoxide system. Continuous stirring promotes the complete removal of bubbles, forming a homogeneous reaction system. A sedimentation and liquid stabilization unit is used to seal and allow the homogenized reaction system to settle, allowing microbubbles and unreacted particles to gradually settle. This sedimentation process stabilizes the system structure, forming a clear and homogeneous reaction liquid in the upper layer. An inert gas purification unit is used to slowly purify the upper layer of reaction liquid formed during sedimentation. A slow inert nitrogen gas flow is introduced into the reaction mixture to displace the reaction liquid, removing residual volatile impurities and solvent vapors, forming an inert protective environment on the surface of the system, and purifying the reaction liquid structure. In the precision filtration and sample purification unit, the nitrogen-purified upper reaction liquid is slowly filtered through a 0.22-micron organic filter membrane to remove residual salt particles and fine suspended matter, obtaining the sample system. In the test sample preparation module, after ultrasonic dissolution, dimethyl sulfoxide is added to the mark to prepare the test sample solution. In the reference standard preparation module, 20 mg each of dimethyl sulfide and dimethyl disulfide are weighed, dissolved and diluted with dimethyl sulfoxide, and prepared into solutions per 1 mL. A reference solution containing 10 μg each of methyl sulfide and dimethyl disulfide was prepared. A gas chromatography detection module was used for detection. The test solution and reference solution were injected separately and separated on a capillary column using 6% cyanopropylphenyl-94% dimethyl polysiloxane as the stationary phase. The initial temperature was set at 40℃ and held for 5 minutes, then increased to 180℃ at a rate of 30℃ per minute and held for 5 minutes. The injection port temperature was 180℃, the detector temperature was 230℃, the injection volume was 0.5 μL, and the split ratio was 10:

1. The content of methyl sulfide, dimethyl disulfide, and unknown impurities in methanesulfonic acid was determined by comparing the chromatograms.

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