Method for measuring content of trimethylchlorosilane

Abstract

The invention provides a method for measuring the content of trimethylchlorosilane, and relates to the field of chemical engineering, and the specific method is as follows: preparing a trimethylchlorosilane contrast solution and a test solution, detecting by adopting a gas chromatographic method, and calculating the content by using an external standard method. The method is characterized in that a capillary chromatographic column taking 6%-cyanopropyl phenyl-94%-polydimethylsiloxane as a stationary phase is adopted, n-heptane is taken as a solvent, carrier gas is nitrogen, and effective separation of trimethylchlorosilane and impurities is realized through an optimized gradient heating program. The method is high in precision (RSD is less than or equal to 2%), good in accuracy (average recovery rate is 99.6%), excellent in linear relation (r is equal to 1.000), simple and convenient to operate and free of derivatization step, and is suitable for efficient and reliable determination of trimethylchlorosilane raw materials and residual solvents thereof in drugs (such as erythromycin thiocyanate).

Description

Technical Field

[0001] This invention relates to the field of chemical engineering, and specifically to a method for determining the content of trimethylchlorosilane. Background Technology

[0002] Trimethylchlorosilane (TMCS) is an important organosilicon compound with the chemical formula (CH3)3SiCl. It is a colorless to pale yellow, transparent liquid with a pungent odor, readily deliquescent in air and releasing hydrogen chloride fumes. Due to the simultaneous presence of highly reactive chlorine atoms and hydrophobic trimethylsilane groups in its molecular structure, TMCS is widely used as a key silanizing agent and end-capping agent in organic synthesis, materials science, and industrial production.

[0003] However, trimethylchlorosilanes are often present in complex mixtures (such as low-boiling methylchlorosilanes), and their boiling points may be very close to those of other components, making complete separation on a chromatographic column difficult. Studies have shown that methyldichlorosilane and 2-methyl-2-butene in "low-boiling methylchlorosilane" samples cannot be separated on a single capillary column. This poses challenges for qualitative and quantitative analysis, requiring specialized methods (such as derivative methods) or higher-resolution instruments, and they readily react with water to generate hydrogen chloride gas.

[0004] To overcome this challenge, existing technologies typically employ derivatization reactions to generate stable derivatives for detection, or react them completely with water to determine the chloride ion content. While this is acceptable for processes with lower quality requirements, it is too crude and prone to significant errors in the results for products with higher quantitative requirements. Therefore, a simple and efficient method for determining the content of trimethylchlorosilane is proposed to meet the urgent need for rapid and efficient quality monitoring of pharmaceutical raw materials. Summary of the Invention

[0005] To solve the above-mentioned technical problems, the present invention provides a method for determining the content of trimethylchlorosilane, comprising the following steps: S1. Preparation of control solution: Accurately weigh an appropriate amount of trimethylchlorosilane, place it in the same volumetric flask, add n-heptane to dilute to volume, shake well, and prepare the control solution. S2. Preparation of test solution: Accurately weigh an appropriate amount of test sample, add an appropriate amount of n-heptane to dissolve, shake well, seal, and the test sample is obtained; the test sample is trimethylchlorosilane (test raw material) or a sample containing trimethylchlorosilane (test residue). S3. Gas chromatography was used to detect the control solution and the test solution respectively, and the peak area of ​​trimethylchlorosilane in the chromatogram was recorded. S4. Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

[0006] Preferably, the conditions for the gas chromatography include: Chromatographic column: Capillary column with 6% cyanopropylphenyl-94% polydimethylsiloxane as the stationary phase; Carrier gas: Nitrogen Carrier gas flow rate: 2 mL / min Inlet temperature: 200℃ FID detector temperature: 250℃ Flow split ratio: 5:1 Sample introduction method: split Headspace heating temperature: 85℃ Balancing time: 30 min Column temperature: Initial temperature 40℃, maintain for 8 min, then increase to 120℃ at a rate of 8℃ / min, and maintain for 10 min.

[0007] Preferably, in step S1, the preparation of the control solution specifically involves: accurately weighing approximately 90-110 mg of trimethylchlorosilane and placing it in different 50 mL volumetric flasks, adding n-heptane to dilute to volume, shaking well, and preparing two parallel stock solutions ① and ②. The average peak area obtained from the two control solutions is used as A in the calculation of step S4. 对 .

[0008] Preferably, the carrier gas is nitrogen with a purity of 99.99% or higher.

[0009] Preferably, the chromatographic column is a capillary column with 6% cyanopropylphenyl-94% polydimethylsiloxane as the stationary phase, and has a size of 30m × 0.32mm and 1.8μm.

[0010] Preferably, the initial column temperature is 40°C, maintained for 8 minutes, and then increased to 120°C at a rate of 8°C / min, and maintained for 10 minutes.

[0011] On the other hand, the present invention provides applications of the method for quality control or residue detection of erythromycin thiocyanate or for detection of trimethylchlorosilane raw materials.

[0012] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention utilizes a capillary column with 6% cyanopropylphenyl-94% polydimethylsiloxane as the stationary phase for separation chromatography, effectively separating trimethylchlorosilane from impurities. Using n-heptane as the dissolving solvent avoids interference with target analyte detection, ensuring the accuracy and reliability of the results. Experimental results demonstrate that this method exhibits high precision (RSD ≤ 2%), good accuracy (average recovery rate of 99.6% for trimethylchlorosilane), and perfect linearity (r = 1.000 for trimethylchlorosilane), fully validating its reliability.

[0013] 2. Existing derivatization methods usually require additional reaction steps, harsh reaction conditions (such as strict control of anhydrous and low temperature) or complex post-processing. In contrast, this invention uses n-heptane to dissolve and dilute the sample, eliminating the need for intermediate transfer, extraction or purification operations, which simplifies the experimental process and shortens the sample pretreatment time.

[0014] 3. Through systematic screening and optimization of chromatographic conditions, this invention has determined the optimal flow rate of 2.0 mL / min, the optimal column (a capillary column with 6% cyanopropylphenyl-94% polydimethylsiloxane as the stationary phase, with dimensions of 30 m × 0.32 mm and a film thickness of 1.8 μm), and the optimal column temperature (initial column temperature of 40 °C, maintained for 8 min, then increased to 120 °C at a rate of 8 °C / min, and maintained for 10 min). These key parameters effectively separate the target analyte from impurities, resulting in good peak shape. This avoids abnormal problems such as peak leading edge, tailing, poor resolution, and peak degradation caused by other conditions (e.g., comparative example 2: using isothermal detection at 120 °C, comparative example 1: using a non-polar chromatographic column for detection, and comparative example 3: using methanol as a solvent). Under the condition of FID detector temperature of 250 °C, the target analyte response is sensitive, the method has strong specificity, and there is no interference from blanks.

[0015] 4. The technical solution provided by this invention is not only applicable to the content detection of trimethylchlorosilane, but can also be extended to the quality control of residual solvents of trimethylchlorosilane in other active pharmaceutical ingredients. Attached Figure Description

[0016] Figure 1 The image shows the gas chromatogram of the blank solution from Experiment 1. Figure 2 This is the gas chromatogram of the control solution in Experiment 1; Figure 3 The gas chromatogram of the test solution in Experiment 1; Figure 4 The linear graph of trimethylchlorosilane in Experiment 1; Figure 5 This is the gas chromatogram of the control solution from Example 1; Figure 6 The gas chromatogram of the test liquid in Example 1; Figure 7 This is the gas chromatogram of the control solution in Example 2; Figure 8 The gas chromatogram of the test liquid in Example 2; Figure 9 This is the gas chromatogram of the control solution in Example 3; Figure 10 Here is the gas chromatogram of the test liquid in Example 3; Figure 11 This is the gas chromatogram of the control solution in Example 4; Figure 12 Here is the gas chromatogram of the test solution in Example 4; Figure 13 This is the gas chromatogram of the control solution in Example 5; Figure 14 The gas chromatogram of the test solution in Example 5; Figure 15 This is the gas chromatogram of the control solution in Example 6; Figure 16 Here is the gas chromatogram of the test solution from Example 6; Figure 17 The gas chromatogram of the control solution in Comparative Example 1 is shown below. Figure 18 This is the gas chromatogram of the control solution in Comparative Example 2; Figure 19 This is the gas chromatogram of the control solution in Comparative Example 3. Detailed Implementation

[0017] Example 1 A method for determining the content of trimethylchlorosilane includes the following steps: S1. Preparation of control solution: Accurately weigh about 100 mg of trimethylchlorosilane and place it in different 50 mL volumetric flasks. Add n-heptane to dilute to volume, shake well, and prepare two parallel portions of control solution ① and ②. S2. Preparation of test solution: Accurately weigh 100 mg of test sample, add n-heptane to dilute to 50 ml, shake well, and the solution is ready; S3. The test solution and control solution are detected by gas chromatography, wherein the gas chromatography method adopts a gradient temperature detection method, and the gas chromatography column uses 6%-cyanopropylphenyl-94%-polydimethylsiloxane as the stationary phase and the stationary liquid.

[0018] The carrier gas is nitrogen; the carrier gas flow rate is 2 mL / min; the injection port temperature is 180℃; the FID detector temperature is 250℃; the split ratio is 5:1; the injection method is split; the headspace heating temperature is 85℃; the equilibration time is 30 min; the column temperature is: initial temperature 40℃, maintained for 8 min, then increased to 120℃ at a rate of 8℃ / min, and maintained for 10 min.

[0019] Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对 ×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

[0020] Example 2 A method for determining the content of trimethylchlorosilane includes the following steps: S1. Preparation of control solution: Accurately weigh about 100 mg of trimethylchlorosilane and place it in different 50 mL volumetric flasks. Add n-heptane to dilute to volume, shake well, and prepare two parallel portions of control solution ① and ②. S2. Preparation of test solution: Accurately weigh 100 mg of test sample, add n-heptane to dilute to 50 ml, shake well, and the solution is ready; S3. The test solution and control solution are detected by gas chromatography, wherein the gas chromatography method adopts a gradient temperature detection method, and the gas chromatography column is a capillary column with 6%-cyanopropylphenyl-94%-polydimethylsiloxane as the stationary phase.

[0021] The carrier gas is nitrogen; the carrier gas flow rate is 2 mL / min; the injection port temperature is 220℃; the FID detector temperature is 250℃; the split ratio is 5:1; the injection method is split; the headspace heating temperature is 85℃; the equilibration time is 30 min; the column temperature is: initial temperature 40℃, maintained for 8 min, then increased to 120℃ at a rate of 8℃ / min, and maintained for 10 min.

[0022] Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对 ×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

[0023] Example 3 A method for determining the content of trimethylchlorosilane includes the following steps: S1. Preparation of control solution: Accurately weigh about 100 mg of trimethylchlorosilane and place it in different 50 mL volumetric flasks. Add n-heptane to dilute to volume, shake well, and prepare two parallel portions of control solution ① and ②. S2. Preparation of test solution: Accurately weigh 100 mg of test sample, add n-heptane to dilute to 50 ml, shake well, and the solution is ready; S3. The test solution and control solution are detected by gas chromatography. The gas chromatography method adopts a gradient temperature detection method. The gas chromatography column is a gas chromatography column with 6%-cyanopropylphenyl-94%-polydimethylsiloxane as the stationary phase (size is 30m×0.32mm, film thickness is 1.8μm).

[0024] The carrier gas is nitrogen; the carrier gas flow rate is 2 mL / min; the injection port temperature is 200℃; the FID detector temperature is 230℃; the split ratio is 5:1; the injection method is split; the headspace heating temperature is 85℃; the equilibration time is 30 min; the column temperature is: initial temperature 40℃, maintained for 8 min, then increased to 120℃ at a rate of 8℃ / min, and maintained for 10 min.

[0025] Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对 ×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

[0026] Example 4 A method for determining the content of trimethylchlorosilane includes the following steps: S1. Preparation of control solution: Accurately weigh about 100 mg of trimethylchlorosilane and place it in different 50 mL volumetric flasks. Add n-heptane to dilute to volume, shake well, and prepare two parallel portions of control solution ① and ②. S2. Preparation of test solution: Accurately weigh 100 mg of test sample, add n-heptane to dilute to 50 ml, shake well, and the solution is ready; S3. The test solution and control solution are detected by gas chromatography. The gas chromatography method adopts a gradient temperature detection method. The gas chromatography column is a gas chromatography column with 6%-cyanopropylphenyl-94%-polydimethylsiloxane as the stationary phase (size is 30m×0.32mm, film thickness is 1.8μm).

[0027] The carrier gas is nitrogen; the carrier gas flow rate is 2 mL / min; the injection port temperature is 200℃; the FID detector temperature is 270℃; the split ratio is 5:1; the injection method is split; the headspace heating temperature is 85℃; the equilibration time is 30 min; the column temperature is: initial temperature 40℃, maintained for 8 min, then increased to 120℃ at a rate of 8℃ / min, and maintained for 10 min.

[0028] Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对 ×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

[0029] Example 5 A method for determining the content of trimethylchlorosilane includes the following steps: S1. Preparation of control solution: Accurately weigh about 100 mg of trimethylchlorosilane and place it in different 50 mL volumetric flasks. Add n-heptane to dilute to volume, shake well, and prepare two parallel portions of control solution ① and ②. S2. Preparation of test solution: Accurately weigh 100 mg of test sample, add n-heptane to dilute to 50 ml, shake well, and the solution is ready; S3. The test solution and control solution are detected by gas chromatography. The gas chromatography method adopts a gradient temperature detection method. The gas chromatography column is a gas chromatography column with 6%-cyanopropyl-phenyl-94%-polydimethylsiloxane as the stationary phase (size is 30m×0.32mm, film thickness is 1.8μm).

[0030] The carrier gas is nitrogen; the carrier gas flow rate is 1.8 mL / min; the injection port temperature is 200℃; the FID detector temperature is 250℃; the split ratio is 5:1; the injection method is split; the headspace heating temperature is 85℃; the equilibration time is 30 min; the column temperature is: initial temperature 40℃, maintained for 8 min, then increased to 120℃ at a rate of 8℃ / min, and maintained for 10 min.

[0031] Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对 ×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

[0032] Example 6 A method for determining the content of trimethylchlorosilane includes the following steps: S1. Preparation of control solution: Accurately weigh about 100 mg of trimethylchlorosilane and place it in different 50 mL volumetric flasks. Add n-heptane to dilute to volume, shake well, and prepare two parallel portions of control solution ① and ②. S2. Preparation of test solution: Accurately weigh 100 mg of test sample, add n-heptane to dilute to 50 ml, shake well, and the solution is ready; S3. The test solution and control solution are detected by gas chromatography. The gas chromatography method adopts a gradient temperature detection method. The gas chromatography column is a gas chromatography column with 6%-cyanopropylphenyl-94%-polydimethylsiloxane as the stationary phase (size is 30m×0.32mm, film thickness is 1.8μm).

[0033] The carrier gas is nitrogen; the carrier gas flow rate is 2.2 mL / min; the injection port temperature is 200℃; the FID detector temperature is 250℃; the split ratio is 5:1; the injection method is split; the headspace heating temperature is 85℃; the equilibration time is 30 min; the column temperature is: initial temperature 40℃, maintained for 8 min, then increased to 120℃ at a rate of 8℃ / min, and maintained for 10 min.

[0034] Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对 ×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

[0035] Example 7 A method for determining the content of trimethylchlorosilane includes the following steps: S1. Preparation of control solution: Accurately weigh about 100 mg of trimethylchlorosilane and place it in different 50 mL volumetric flasks. Add n-heptane to dilute to volume, shake well, and prepare two parallel portions of control solution ① and ②. S2. Preparation of test solution: Accurately weigh 100 mg of test sample, add n-heptane to dilute to 50 ml, shake well, and the solution is ready; S3. The test solution and control solution are detected by gas chromatography. The gas chromatography method adopts a gradient temperature detection method. The gas chromatography column is a gas chromatography column with 6%-cyanopropylphenyl-94%-polydimethylsiloxane as the stationary phase (size is 30m×0.32mm, film thickness is 1.8μm).

[0036] The carrier gas is nitrogen; the carrier gas flow rate is 2.0 mL / min; the injection port temperature is 200℃; the FID detector temperature is 250℃; the split ratio is 5:1; the injection method is split; the headspace heating temperature is 85℃; the equilibration time is 30 min; the column temperature is: initial temperature 40℃, maintained for 8 min, then increased to 120℃ at a rate of 8℃ / min, and maintained for 10 min.

[0037] Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对 ×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

[0038] Comparative Example 1 Unlike Example 7, the chromatographic column in step S3 is a gas chromatographic column with 100% dimethyl polysiloxane as the stationary phase.

[0039] Comparative Example 2 Unlike Example 7, the column temperature in step S3 is 120°C.

[0040] Comparative Example 3 Unlike Example 7, the solvent used in step S2 is methanol.

[0041] Experimental Section Experiment 1 1. Instruments and Gas Chromatography Conditions Instruments: Thermo Fisher GC-1600 gas chromatograph, Agilent DB-624 column with dimensions of 30m × 0.32mm and a film thickness of 1.8μm, and Mettler Toledo XPR205DR electronic balance; Chromatographic conditions: Detector: FID (temperature 250℃); Flow rate: 2.0 mL / min; Injection method: split injection (split ratio: 5:1); Column temperature: initial temperature 40℃, hold for 8 min, increase to 120℃ at a rate of 8℃ / min, hold for 10 min; Headspace heating temperature: 85℃; Equilibrium time: 30 min; Injector temperature: 200℃; Carrier gas: nitrogen.

[0042] 2. Materials Trimethylchlorosilane: Analytical grade reagent, batch number S11922410001, Sinopharm Chemical Reagent Co., Ltd., purity: 99.2%; n-Heptane: Analytical grade reagent, batch number S2762503001, provided by Tianjin Kemei Chemical Reagent Co., Ltd., with a purity of ≥99.5%.

[0043] 3. Measurement of different test samples Blank solution: n-heptane; Control solutions: Accurately weigh approximately 100 mg of trimethylchlorosilane and place it in different 50 mL volumetric flasks. Add n-heptane to dilute to volume, shake well, and prepare two parallel solutions to obtain control solutions ① and ②.

[0044] Test solution: Accurately weigh 100 mg of the test sample, add n-heptane to dilute to 50 ml, shake well, and the solution is ready; Using a split-flow method, samples were injected and detected separately, and the peak areas were recorded. These peak areas were then substituted into the formula: Trimethylchlorosilane (%) = (A... 试 / A 对 )×(W 对 ×C 对 / V 对 The content of trimethylchlorosilane was obtained by multiplying (V / W) by 100%, and the results are shown in Table 1.

[0045] Table 1 Results of Trimethylchlorosilane Content Determination

[0046] 4. Methodological Validation 4.1 Specificity For the blank solution, control solution, and test solution determined by the above method, please refer to [reference needed]. Figures 1-3 The solvent peak does not interfere with the determination of trimethylchlorosilane.

[0047] 4.2 Linear Within the trimethylchlorosilane concentration range of 0.6124 mg / ml to 3.0325 mg / ml, the concentration-area linear relationship was good. Figure 4 Linear equation: Y = 2.8110x - 0.0919, correlation coefficient: 1.000.

[0048] 4.3 Precision Six parallel determinations were performed on the same batch of samples (trimethylchlorosilane batch number: YF-YP20251103-001), and each sample was injected into a gas chromatograph. The results showed that the average content of trimethylchlorosilane was 98.5% and the RSD of trimethylchlorosilane was 0.9%. Six parallel test solutions were prepared at two different times using different instruments and injected into the gas chromatograph (n=12). The results showed that the average content of trimethylchlorosilane was 98.6% and the RSD of trimethylchlorosilane was 0.7%.

[0049] 4.4 Accuracy Test solution: Accurately weigh about 50 mg of the test sample into a 50 ml volumetric flask, dilute with n-heptane, make up to volume, and mix well.

[0050] 80% spiked solution: Accurately weigh about 50 mg of the test sample into a 50 ml volumetric flask, then accurately weigh about 30 mg of the reference sample into the same volumetric flask, add n-heptane to dilute to 50 ml, and mix well.

[0051] 100% spiked solution: Accurately weigh about 50 mg of the test sample into a 50 ml volumetric flask, then accurately weigh about 50 mg of the reference sample into the same volumetric flask, add n-heptane to dilute to 50 ml, and mix well.

[0052] 120% spiked solution: Accurately weigh about 50 mg of the test sample into a 50 ml volumetric flask, then accurately weigh about 70 mg of the reference sample into the same volumetric flask, add n-heptane to dilute to 50 ml, and mix well.

[0053] Table 2 Results of Trimethylchlorosilane Content Recovery

[0054] Experiment 2 The trimethylchlorosilane content was determined using the technical solution of Example 1 (injection port temperature 180℃): the detection results of the control solution are as follows. Figure 5As shown, the retention time of trimethylchlorosilane was 14.335 min, the peak area was 6.4317 pA min, the peak height was 83.12 pA, the asymmetry was 0.98, and the peak shape was normal; the test results of the test solution are as follows. Figure 6 As shown, the retention time of trimethylchlorosilane was 14.335 min, the peak area was 6.4777 pA min, the peak height was 83.32 pA, and the asymmetry was 0.98. The peak shape was consistent with that of the control solution, and there was no interference.

[0055] The determination was performed using the technical solution of Example 2 (injection port temperature 220℃): the detection results of the control solution are as follows. Figure 7 As shown, trimethylchlorosilane had a retention time of 14.348 min, a peak area of ​​7.7538 pA / min, a peak height of 99.30 pA, an asymmetry of 0.99, and a regular peak shape; the test solution detection results are as follows. Figure 8 As shown, the retention time of trimethylchlorosilane was 14.348 min, the peak area was 7.8295 pA min, the peak height was 99.63 pA, the asymmetry was 0.99, and no abnormalities were detected.

[0056] The determination was performed using the technical solution of Example 3 (detector temperature 230℃): the detection results of the control solution are as follows. Figure 9 As shown, the retention time of trimethylchlorosilane was 14.340 min, the peak area was 6.9593 pA min, the peak height was 89.55 pA, the asymmetry was 0.99, and the peak shape was normal; the test results of the test solution are as follows. Figure 10 As shown, trimethylchlorosilane has a retention time of 14.340 min, a peak area of ​​7.0421 pA min, a peak height of 89.92 pA, an asymmetry of 0.99, and a stable response.

[0057] The determination was performed using the technical solution of Example 4 (detector temperature 270℃): the detection results of the control solution are as follows. Figure 11 As shown, the trimethylchlorosilane peak shape is normal; the test results of the test solution are as follows. Figure 12 As shown, the peak shape matches that of the control solution, with no interference from extraneous peaks.

[0058] The determination was performed using the technical solution of Example 5 (carrier gas flow rate 1.8 mL / min): the detection results of the control solution are as follows. Figure 13 As shown, the trimethylchlorosilane peak shape is normal; the test results of the test solution are as follows. Figure 14 As shown, the separation effect is good and meets the detection requirements.

[0059] The determination was performed using the technical solution of Example 6 (carrier gas flow rate 2.2 mL / min): the detection results of the control solution are as follows. Figure 15 As shown, the trimethylchlorosilane peak shape is normal; the test results of the test solution are as follows. Figure 16 As shown, the peak shape is symmetrical and the response is stable.

[0060] The determination was performed using the technical solution described in Example 7 (injector temperature 200℃ + carrier gas flow rate 2.0 mL / min + detector temperature 250℃): The detection results for the control solution are as follows. Figure 2 As shown, trimethylchlorosilane had a retention time of 14.093 min, a peak area of ​​7.2194 pA / min, a peak height of 90.45 pA, an asymmetry of 1.00, and the best peak shape; the test solution detection results are as follows. Figure 3 As shown, the retention time of trimethylchlorosilane was 14.100 min, the peak area was 5.5114 pA min, the peak height was 69.93 pA, and the asymmetry was 0.99, which was consistent with the peak shape of the control solution, verifying the reliability of the method.

[0061] The detection was performed using the technique described in Comparative Example 1 (replacing the gas chromatographic column with a 100% dimethylpolysiloxane stationary phase instead of a 6% cyanopropylphenyl-94% polydimethylsiloxane stationary phase gas chromatographic column), and the results are as follows. Figure 17 As shown in the control solution: trimethylchlorosilane had a retention time of 10.187 min, an abnormal peak shape, and an early elution, making it impossible to effectively separate from impurities. Therefore, the test solution was not tested.

[0062] The test was conducted using the technical solution of Comparative Example 2 (changing the gradient heating mode to a constant temperature of 120℃), and the results are as follows. Figure 18 As shown in the control solution: the trimethylchlorosilane peak separation was poor, and it was impossible to distinguish the target analyte from potential impurities, so the test solution was not tested.

[0063] The detection was performed using the technique described in Comparative Example 3 (with the dissolving solvent replaced by methanol), and the results are as follows: Figure 19 As shown in the control solution: Trimethylchlorosilane showed significant degradation and an increase in impurity peaks, which seriously interfered with the qualitative and quantitative analysis of the target analyte. Therefore, the test solution was not tested.

Claims

1. A method for determining the content of trimethylchlorosilane, characterized in that, Includes the following steps: S1. Preparation of control solution: Weigh trimethylchlorosilane reference standard, add n-heptane to dilute and bring to volume, shake well, and prepare control solution; S2. Preparation of test solution: Weigh the test sample, add n-heptane to dilute and bring to volume to prepare the test solution; S3. Gas chromatography was used to detect the control solution and the test solution respectively, and the peak area of ​​trimethylchlorosilane was recorded. S4. Calculate the content of trimethylchlorosilane: Trimethylchlorosilane (%) = (A 试 / A 对 )×(W 对 ×C 对 / V 对 ) × (V / W) × 100%, where: A 试 The peak area of ​​trimethylchlorosilane in the test solution; A 对 The peak area of ​​trimethylchlorosilane in the control solution; C 对 The content (%) of trimethylchlorosilane in the control solution; W 对 The sample weight (mg) of trimethylchlorosilane in the control solution; V 对 This is the dilution factor for the control solution; V is the dilution factor of the test solution; W represents the sample weight.

2. The method as described in claim 1, characterized in that, The conditions for the gas chromatography method include: Chromatographic column: Capillary column with 6% cyanopropylphenyl-94% polydimethylsiloxane as the stationary phase; Carrier gas: Nitrogen, purity ≥ 99.99%; Carrier gas flow rate: 1.8-2.2 mL / min; Inlet temperature: 180-220℃; Detector: FID detector, temperature 230-270℃; Injection method: split injection, split ratio 5:1; Headspace heating temperature: 80-90℃, equilibrium time: 30min; Column temperature program: Initial temperature 40-50℃, maintain for 8 min, increase to 120℃ at 8℃ / min, maintain for 10 min.

3. The method as described in claim 2, characterized in that, The chromatographic column is a DB-624 column with dimensions of 30m × 0.32mm × 1.8μm.

4. The method as described in claim 2, characterized in that, The carrier gas flow rate is 2.0 mL / min.

5. The method as described in claim 2, characterized in that, The injection port temperature is 200℃.

6. The method as described in claim 2, characterized in that, The temperature of the FID detector is 250°C.

7. The method as described in claim 2, characterized in that, The headspace heating temperature is 85°C.

8. The method as described in claim 1, characterized in that, The preparation method of the control solution in step S1 is as follows: Weigh 90-110 mg of trimethylchlorosilane reference standard, place it in a 50 mL volumetric flask, add n-heptane to make up to volume, shake well, and prepare two parallel control solutions. The average peak area obtained from the two control solutions is used as A in the calculation of step S4. 对 .

9. The method as described in claim 1, characterized in that, The preparation method of the test solution in step S2 is as follows: weigh 90-110 mg of the test sample, add n-heptane to dilute and bring the volume to 50 mL, shake well, and seal.

10. The application of the method as described in any one of claims 1-9 in drug quality control or residual solvent detection, characterized in that, Used for quality control or residue detection of erythromycin thiocyanate or for detection of trimethylchlorosilane raw materials.

Images