Method for detecting tert-butylamine residue in S-acetamidomethyl-L-cysteine-L-leucine tert-butyl ester
Detection of tert-butylamine residues in S-acetylamine methyl-L-cysteine-L-leucine tert-butyl ester by gas chromatography has solved the problem of lack of effective detection methods in the prior art, and achieved high sensitivity and accuracy The test results ensure the quality of the pharmaceutical intermediates.
Patent Information
- Application Number
- CN202411578287.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-07
- Publication Date
- 2025-01-03
AI Technical Summary
The prior art lacks effective methods to detect the residual amount of tert-butylamine in S-acetylamine-L-cysteine-L-leucine tert, making it difficult to ensure the quality of pharmaceutical intermediates.
Using gas chromatography, the specific steps include dissolving the sample using methanol, analyzing through a Shimadzu GC-2030 chromatograph and a hydrogen flame detector, combining specific chromatographic columns and conditions, and using the boiling point difference between tert-butylamine and methanol to achieve baseline-level separation, and Quantitative testing is carried out through the program heating procedure.
Accurate, fast and highly sensitive detection of tert-butylamine residues in S-acetamethylene-L-cysteine-L-leucine tert-butyl ester, ensuring linear stability and selectivity of detection, and providing detection To ensure the quality of the drug.
Smart Images
Figure CN119246730A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a method for detecting residual tert-butylamine in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester. Background Art
[0002] Tert-butylamine, also known as "2-methyl-2-aminopropane", is an organic synthetic raw material used to synthesize medicines, rubber vulcanization accelerators, pesticides, fungicides and dye colorants. It can also be used as a solvent. It is a good organic solvent in the recrystallization process of S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester. However, tert-butylamine is irritating and corrosive to the human body; it is also a highly toxic substance. S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester is a pharmaceutical intermediate. In order to ensure the quality of the raw material, the residual amount of tert-butylamine needs to be controlled. At present, there is no method for detecting the residual tert-butylamine in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester. Summary of the invention
[0003] The invention provides a method for detecting tert-butylamine residue in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester, mainly providing an accurate and simple gas chromatography method for detecting tert-butylamine residue, thereby ensuring the quality of S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester as a pharmaceutical intermediate.
[0004] The present invention adopts the following technical scheme: a method for detecting tert-butylamine residue in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester, which comprises the following steps: Step 1: Prepare the measuring reagents, which include methanol-chromatographic grade.
[0005] Step 2: Weigh the product sample and place it in a volumetric flask, add pure methanol, dissolve it by ultrasonic at 25°C, and finally filter the sample with a polypropylene organic filter membrane and perform gas chromatography analysis.
[0006] Step three, perform gas chromatography determination: the chromatographic conditions are that the sample chamber temperature is room temperature, automatic sample injector, the chromatographic column is Shimadzu SH-Rxi-624sil, a hydrogen flame detector is used, the vaporization temperature is 280°C, the detector temperature is 300°C, the column temperature: the starting temperature is 80°C, maintained for 5 minutes, then increased to 280°C at a rate of 20°C / min, maintained for 5 minutes, the carrier gas flow rate is 2mL / min, the split ratio is 1:40, and a programmed temperature rise program is used.
[0007] The chromatograph used in the gas chromatography determination is a Shimadzu GC-2030 chromatograph which uses a hydrogen flame detector.
[0008] The invention has the following beneficial effects: the invention provides a method for detecting the residual tert-butylamine in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester, the method is reliable, accurate, highly sensitive, and the standard curve is linear and stable; the invention mainly utilizes the difference between the boiling point of tert-butylamine (46 DEG C) and the boiling point of methanol (65.4 DEG C), and can complete baseline separation on a chromatographic column, and the tert-butylamine exists in the form of residual solvent in the S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester, so the high temperature of the injection port of the gas chromatograph is utilized to make the sample instantly change from a liquid state to a gas state, and then through the adsorption and separation of the capillary chromatographic column, the chemical signal is converted into an electrical signal by using a hydrogen flame detector, so that the residual amount of the tert-butylamine is separated and quantitatively detected on a chromatographic workstation, providing a basis. BRIEF DESCRIPTION OF THE DRAWINGS
[0009] Figure 1 Spectrum of tert-butylamine standard 1 detected by Shimadzu GC-2030 chromatograph.
[0010] Figure 2 Spectrum of tert-butylamine standard sample 2 detected by Shimadzu GC-2030 chromatograph.
[0011] Figure 3 Spectrum of tert-butylamine standard sample 3 detected by Shimadzu GC-2030 chromatograph.
[0012] Figure 4 Standard curve evaluation table detected by Shimadzu GC-2030 chromatograph.
[0013] Figure 5 Sample spectrum detected by Shimadzu GC-2030 chromatograph. DETAILED DESCRIPTION
[0014] The measuring process of the present invention is further described below by way of examples.
[0015] Experimental Section Main instruments: The chromatographic determination process is as follows: the chromatographic conditions are that the sample chamber temperature is room temperature, automatic sample injector, the chromatographic column is Shimadzu SH-Rxi-624sil, a hydrogen flame detector is used, the vaporization temperature is 280°C, the detector temperature is 300°C, the column temperature: the starting temperature is 80°C, maintained for 5 minutes, then increased to 280°C at a rate of 20°C / min, maintained for 5 minutes, the carrier gas flow rate is 2mL / min, the split ratio is 1:40, and a programmed temperature program is used.
[0016] Shimadzu GC-2030 gas chromatograph, equipped with hydrogen flame detector, Shimadzu SH-Rxi-624sil chromatographic column, column size 30m × 0.32mm, 0.18μm; ultrasonic extractor (KQ5200E, Zhengzhou Ketai Experimental Equipment Co., Ltd.), 0.22 μm polypropylene organic filter membrane (Shanghai Anpu Scientific Instrument Co., Ltd.), electronic analytical balance (CPA225D, Sartorius Scientific Instrument (Shanghai) Co., Ltd.).
[0017] Main reagents: The reagents used for the measurement included methanol (chromatographic grade, Merck, Germany).
[0018] Sample pretreatment: Weigh about 10 mg of the sample and place it in a 10 mL glass volumetric flask. Add 5 ml of pure methanol and dissolve it under ultrasonic conditions at 25 °C for 3 min. Finally, filter the sample with a 0.22 µm polypropylene organic filter membrane and perform gas chromatography analysis.
[0019] Chromatographic conditions: The sample chamber temperature was room temperature, the autosampler injection volume was 1.0µL, the chromatographic column was: Shimadzu SH-Rxi-624sil, the column size was 30m × 0.32mm, 0.18μm; a hydrogen flame detector was used, the vaporization temperature was 280°C, the detector temperature was 300°C, the column temperature was: starting temperature 80°C, maintained for 5 minutes, then increased to 280°C at a rate of 20°C / min, maintained for 5 minutes, the carrier gas flow rate was 2mL / min, the split ratio was 1:40, and a programmed temperature program was used. The detected tert-butylamine standard sample spectrum is shown in Figure 1-Figure 3 , the standard curve evaluation table for the test is shown in Figure 4 , the sample spectrum of the test is shown in Figure 5 .
[0020] Currently, S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester is solid on the market. The sample measured in the present invention is S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester produced by Jier Biochemical (Shanghai) Co., Ltd.
[0021] The results of detecting the residual tert-butylamine in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester using the method show that the method is fast, accurate, highly sensitive, and has good selectivity, and has practical application value. The present invention establishes a determination method by detecting the residual tert-butylamine in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester. The method successfully performs quantitative detection, can accurately detect the residual amount of tert-butylamine in the amino acids of the sample, and has good stability in the detection process.
Claims
1. A method for detecting tert-butylamine residue in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester; the method comprising: The following steps are involved: Step 1, preparation of sample solution: weigh the product sample and place it in a volumetric flask, add pure methanol, dissolve it by ultrasonic at 25°C, and finally filter the sample with a polypropylene organic filter membrane and perform HPLC analysis; Step 2: Perform gas chromatography determination: automatic sample injector, chromatographic column is Shimadzu SH-Rxi-624sil, hydrogen flame detector is used, carrier gas is high-purity nitrogen, vaporization temperature: 280°C, detector temperature: 300°C, column temperature adopts programmed temperature rise program.
2. The method for detecting tert-butylamine residue in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester according to claim 1, characterized in that: The chromatograph used in the gas chromatography determination is Shimadzu GC-2030 gas chromatograph, which uses a hydrogen flame detector.
3. The method for detecting residual tert-butylamine in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester according to claim 1, characterized in that: The chromatographic column has a size of 30.0m × 0.32mm, 1.8μm.
4. The method for detecting tert-butylamine residue in S-acetylaminomethyl-L-cysteine-L-leucine tert-butyl ester according to claim 1, characterized in that: The programmed temperature rise program is: starting temperature 80°C, maintained for 5 minutes, then increased to 280°C at a rate of 20°C / min, maintained for 5 minutes, carrier gas flow rate: 2mL / min, split ratio: 1:40.