Method for detecting ammonia in methamphetamine

Abstract

The application belongs to the technical field of pharmaceutical analysis, and particularly relates to a detection method of ammonia in methamphetamine, which is a convenient, efficient and accurate detection method for solving the problem of ammonia detection in methamphetamine. The method uses gas chromatography to detect the content of ammonia in methamphetamine, has low detection cost, and is convenient for quality control of methamphetamine. The method is convenient, efficient and accurate, and fully meets the guiding principles of method verification of Chinese Pharmacopoeia in terms of system applicability, repeatability, specificity and accuracy, and can be used for quality control of methamphetamine.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical analysis technology, specifically relating to a method for detecting ammonia in methylamine. Background Technology

[0002] Methylamine, with the chemical formula CH5NO, is a colorless liquid with an ammonia odor at room temperature. It is widely used in the pharmaceutical intermediate industry and is a key material in the synthesis of reganosin. During the preparation of methylamine active pharmaceutical ingredient (API), ammonia may be generated in methylamine, affecting its quality and ultimately impacting the reganosin API. The presence of ammonia in methylamine may generate corresponding impurities I in the reganosin product. This increases the necessity of finished product research. If the ammonia level in the raw material methylamine is well controlled, the research on regano products can be reduced.

[0003] Currently, methods for ammonia detection, including Nessler's reagent spectrophotometry, salicylic acid spectrophotometry, and indophenol blue spectrophotometry, lack specificity and have poor quantitative accuracy. Since ammonia has relatively weak ultraviolet absorption, this invention employs gas chromatography-TCD detection, which provides a better response and can accurately quantify the actual ammonia content in methylamine. There are few published reports on methods for detecting ammonia in methylamine. This invention is the first to disclose a gas chromatography method for detecting ammonia in methylamine, reducing detection costs and providing a convenient, efficient, and accurate detection method for solving the problem of ammonia detection in methylamine. This method can detect the ammonia content in methylamine, facilitating the quality control of methylamine. Summary of the Invention

[0004] This invention provides a method for detecting ammonia in methylamine. To address the problem of ammonia detection in methylamine, this method offers a convenient, efficient, and accurate approach. It employs gas chromatography to detect the ammonia content in methylamine, resulting in low detection costs and facilitating quality control of methylamine. This method is convenient, efficient, and accurate, fully complying with the guidelines for method validation in the Chinese Pharmacopoeia in terms of system applicability, repeatability, specificity, and accuracy. It can be used for the quality control of methylamine.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A method for detecting ammonia in methylamine, the method comprising the following steps:

[0007] (1) Prepare solutions: prepare blank solution, reference solution, limit of quantitation solution, selective solution, water positioning solution and test solution respectively.

[0008] (2) Determination method: The content of ammonia in methanethiol was determined by gas chromatography. After the system stabilized, blank solution, reference solution, limit of quantitation solution, selective solution, water positioning solution and test solution were injected respectively, and the chromatograms were recorded.

[0009] The chromatographic conditions were as follows: Column: ultra-inert weakly polar capillary column; column temperature: 40℃ for 10 min, then increased to 250℃ at a rate of 20℃ / min and held for 5 min; injection port temperature: 200℃; detector type: TCD (thermal conductivity detector); detector temperature: 250℃; split ratio: 30:1; carrier gas: N2; flow rate: 1.5 ml / min; injection volume: 5 μl.

[0010] Furthermore, the chromatographic column is an Agilent CP-Volamine 60m × 0.32mm column or a column of equivalent polarity or performance; the blank solution is dimethyl sulfoxide; the reference solution is prepared by placing an appropriate amount of ammonia stock solution in a volumetric flask, diluting it to the mark with blank solution, and shaking well; the ammonia stock solution is prepared by placing an appropriate amount of ammonia water in a volumetric flask, diluting it to the mark with blank solution, and shaking well; the limit of quantitation solution is prepared by placing an appropriate amount of reference solution in a volumetric flask, diluting it to the mark with blank solution, and shaking well; the water positioning solution is prepared by placing an appropriate amount of water in a volumetric flask, diluting it to the mark with blank solution, and shaking well; the test solution is prepared by placing an appropriate amount of methylamine sample in a volumetric flask, diluting it to the mark with blank solution, and shaking well; the selectivity solution is prepared by placing an appropriate amount of methylamine sample and an appropriate amount of ammonia stock solution in a volumetric flask, diluting it to the mark with blank solution, and shaking well.

[0011] This invention provides a convenient, efficient, and accurate detection method for the problem of ammonia detection in methylamine, which can be used for the quality control of methylamine. This patented method can detect the ammonia content in methylamine, thereby effectively ensuring medication safety and facilitating the quality control of methylamine. Attached Figure Description

[0012] Figure 1 This is the spectrum of the blank solution in this invention.

[0013] Figure 2 This is a chromatogram of the reference solution of the present invention.

[0014] Figure 3 This is a chromatogram of the solution with the limit of quantitation of this invention.

[0015] Figure 4 This is a water positioning solution spectrum for the present invention.

[0016] Figure 5 This is a spectrum of the test solution used in this invention.

[0017] Figure 6 This is a selective solution spectrum of the present invention. Implementation

[0018] The present invention is further illustrated by the following examples, but these are not intended to limit the invention. Example 1

[0019] Preparation of solution:

[0020] Diluent: Dimethyl sulfoxide;

[0021] Blank solution: diluent;

[0022] Ammonia stock solution: Accurately weigh approximately 3.0 g of ammonia solution and place it in a 25 ml volumetric flask. Dilute to the mark with diluent and mix well. (Ammonia solution concentration: 0.12 g / ml, equivalent to ammonia concentration: 0.03 g / ml)

[0023] Reference solution: Accurately measure 2.0 ml of ammonia stock solution and place it in a 20 ml volumetric flask. Dilute to the mark with diluent and mix well. (Ammonia concentration: 12 mg / ml, equivalent to ammonia concentration: 3 mg / ml)

[0024] Limit of Quantitation Solution: Accurately measure 2.0 ml of the reference solution into a 20 ml volumetric flask, dilute to the mark with diluent, and mix well. (Ammonia concentration: 1.2 mg / ml, equivalent to ammonia concentration: 0.3 mg / ml)

[0025] Aqueous positioning solution: Accurately weigh approximately 2.25g of water and place it in a 25ml volumetric flask. Dilute to the mark with diluent and mix well. Then measure 2.0ml of the above solution and place it in a 20ml volumetric flask. Dilute to the mark with diluent and mix well. (Concentration: 9mg / ml)

[0026] Test solution: Accurately weigh approximately 12g of the methylamine sample and place it in a 20ml volumetric flask. Dilute to the mark with diluent and mix well. (Concentration: 0.6g / ml)

[0027] Selective solution: Accurately weigh approximately 12g of the methylamine sample and place it in a 20ml volumetric flask. Accurately measure 2.0ml of ammonia stock solution and place it in the same flask. Dilute to the mark with diluent and mix well. (Concentration: methylamine 0.6g / ml, ammonia concentration: 12mg / ml, equivalent to ammonia concentration: 3mg / ml)

[0028] Note: The ammonia content in the ammonia solution is 25%.

[0029] Dimethyl sulfoxide: HPLC; Ammonia (25%): Purchased; Water: Ultrapure water;

[0030] (2) Chromatographic conditions:

[0031] Chromatographic columns: Gas chromatographs equipped with thermal conductivity detectors, direct injectors; ultra-inert weakly polar capillary columns (such as Agilent CP-Volamine 60m × 0.32mm or columns with equivalent polarity).

[0032] Column temperature: 40℃ for 10 min, then increase to 250℃ at 20℃ / min and hold for 5 min;

[0033] Inlet temperature: 200℃; Detector temperature: 250℃;

[0034] Split ratio: 30:1; Carrier gas: N2;

[0035] Flow rate: 1.5 ml / min; Injection volume: 5 μl.

[0036] (3) Measurement method:

[0037] After the system stabilizes, inject one blank solution (or 1-3 injections if necessary), one reference solution, one limit of quantitation solution, one water positioning solution, one test solution, and one selective solution. Record the chromatogram. The S / N value of the ammonia peak in the limit of quantitation solution should be ≥10.

[0038] Ammonia (%) = (RU / Rs) × (Cs / CU) × 100

[0039] Where: RU: Peak area of ​​ammonia in the spectrum of the test solution;

[0040] Rs: Peak area of ​​ammonia in the reference solution spectrum;

[0041] Cs: Concentration of ammonia in the reference solution (mg / ml);

[0042] CU: Concentration of the test solution (mg / ml).

[0043] Result determination:

[0044] Example 2: System Applicability

[0045] System suitability was determined by measuring the sensitivity of ammonia in the sensitivity solution; the S / N value of ammonia was required to be ≥10. Approximately 3.0 g of ammonia solution was accurately weighed and placed in a 25 ml volumetric flask. Dilute to the mark with diluent and mix well. 2.0 ml of the above solution was accurately measured and placed in a 20 ml volumetric flask. Dilute to the mark with diluent and mix well. This was then used as the sensitivity solution. The solution was injected and measured according to the chromatographic conditions in Example 1, and the chromatogram was recorded. The experiment showed that the S / N value of ammonia in the sensitivity solution was >10, thus meeting the system suitability requirements.

[0046] Example 3: Specificity

[0047] Specificity is determined by assessing whether the blank solution interferes with ammonia detection, and the resolution between ammonia and adjacent peaks should meet the requirements. Accurately weigh approximately 3.0 g of ammonia solution and place it in a 25 ml volumetric flask. Dilute to the mark with diluent and mix well; this serves as the ammonia stock solution. Accurately weigh approximately 12 g of methylamine sample and place it in a 20 ml volumetric flask. Accurately measure 2.0 ml of the ammonia stock solution into the same flask, dilute to the mark with diluent, and mix well; this serves as the selective solution.

[0048] The chromatographic conditions of Example 1 were followed. The blank solution did not interfere with the detection of methylamine, and the resolution between ammonia and adjacent peaks in the selective solution was ≥1.5.

[0049] Example 4: Limit of Detection and Limit of Quantification

[0050] The detection limit is obtained by measuring the ratio of the response signal to noise of each component ≥ 3, and the quantitation limit is obtained by measuring the ratio of the response signal to noise of each component ≥ 10. Approximately 3.0 g of ammonia solution was accurately weighed and placed in a 25 ml volumetric flask. Dilute to the mark with diluent and mix well. 2.0 ml of the above solution was accurately measured and placed in a 20 ml volumetric flask. Dilute to the mark with diluent and mix well. Another 2.0 ml of the above solution was accurately measured and placed in a 20 ml volumetric flask. Dilute to the mark with diluent and mix well to obtain the LOQ solution. 5 ml of the LOQ solution was placed in a 10 ml volumetric flask and diluted to the mark with diluent to obtain the LOD solution. After the system stabilized, detection was performed under the chromatographic conditions of Example 1, and the chromatogram was recorded. The experiment showed that the S / N value of ammonia in the LOQ solution was > 10, and the S / N value of ammonia in the LOD solution was > 3, indicating that the method has good sensitivity.

[0051] Example 5: Linear

[0052] Ammonia was analyzed at six concentration points within the LOQ–150% index concentration range. A curve was plotted with concentration on the x-axis and peak area on the y-axis. The curve was required to be linear within the LOQ–150% index concentration range, with a linear correlation coefficient R² ≥ 0.99. Appropriate amounts of the reference solution were prepared into solutions at the limit of quantitation (LOQ), 50%, 80%, 100%, 120%, and 150%, respectively. After the system stabilized, detection was performed under the chromatographic conditions of Example 1. The experiment showed that ammonia exhibited good linearity within the LOQ–150% index concentration range, with a linear correlation coefficient R² ≥ 0.99.

[0053] Example 6: Precision

[0054] Repeatability: Six test solutions were tested, with the RSD of ammonia determination results in all six solutions ≤ 2.0%. Approximately 3.0 g of ammonia solution was accurately weighed and placed in a 25 ml volumetric flask. Dilute to the mark with diluent and mix well; this serves as the ammonia stock solution. Approximately 12 g of methylamine sample was accurately weighed and placed in a 20 ml volumetric flask. 2.0 ml of the ammonia stock solution was accurately added to the same flask, diluted to the mark with diluent, and mixed well; this serves as the repeatability solution. Six aliquots were prepared using the same method. After the system stabilized, detection was performed under the chromatographic conditions of Example 1. The results showed that the RSD of ammonia determination results in the six repeatability solutions was ≤ 2.0%, indicating good precision of the method.

[0055] Example 7: Solution Stability

[0056] The test solution was examined after being left at room temperature for 0, 24, and 48 hours. The ammonia content in the sample solution did not change significantly, indicating that the sample solution was relatively stable within 48 hours.

[0057] The accuracy of the method is ensured by examining its system suitability, specificity, detection limit and quantitation limit, linearity, precision and solution stability.

Claims

1. A method for detecting ammonia in methyl alcohol, characterized by, The detection method comprises the following steps: (1) preparing solutions, respectively preparing blank solution, control solution, limit of quantification solution, selective solution, water positioning solution and test solution; (2) determination method: the content of ammonia in methenamine is determined by gas chromatography, after the system is stable, respectively, blank solution, control solution, limit of quantification solution, selective solution, water positioning solution and test solution are added, and the chromatogram is recorded; The chromatographic conditions are as follows: chromatographic column: prepared thermal conductivity detector, Agilent CP-Volamine 60m*0.32mm, column temperature: 40℃ for 10min, increased to 250℃ at 20℃ / min, and kept for 5min; injection port temperature: 200℃; detector temperature: 250℃; split ratio: 30:1; carrier gas: N2; flow rate: 1.5ml / min; injection volume: 5ul; The blank solution is dimethyl sulfoxide; The control solution: take appropriate amount of ammonia stock solution in a volumetric flask, add blank solution to dilute to the scale, shake well; The ammonia stock solution: take appropriate amount of ammonia water in a volumetric flask, add blank solution to dilute to the scale, shake well; The limit of quantification solution: take appropriate amount of control solution in a volumetric flask, add blank solution to dilute to the scale, shake well; Water positioning solution: take appropriate amount of water in a volumetric flask, add blank solution to dilute to the scale, shake well; Test solution: take appropriate amount of methenamine sample in a volumetric flask, add blank solution to dilute to the scale, shake well; Selective solution: take appropriate amount of methenamine sample and appropriate amount of ammonia stock solution in a volumetric flask, add blank solution to dilute to the scale, shake well.

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