CN115980226A - Method for determining residual amount of trichloromethane in nitrophenylpyridone - Google Patents
Method for determining residual amount of trichloromethane in nitrophenylpyridone Download PDFInfo
- Publication number
- CN115980226A CN115980226A CN202310032373.6A CN202310032373A CN115980226A CN 115980226 A CN115980226 A CN 115980226A CN 202310032373 A CN202310032373 A CN 202310032373A CN 115980226 A CN115980226 A CN 115980226A
- Authority
- CN
- China
- Prior art keywords
- solution
- nitrophenylpyridone
- temperature
- keeping
- trichloromethane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 title claims abstract description 74
- 229960001701 chloroform Drugs 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title claims abstract description 35
- RJHUKYBALKLHRW-UHFFFAOYSA-N 4-nitro-3-phenyl-1H-pyridin-2-one Chemical compound [N+](=O)([O-])C1=C(C(=NC=C1)O)C1=CC=CC=C1 RJHUKYBALKLHRW-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000002347 injection Methods 0.000 claims description 11
- 239000007924 injection Substances 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 239000007789 gas Substances 0.000 claims description 4
- 239000013557 residual solvent Substances 0.000 claims description 4
- 230000005540 biological transmission Effects 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 230000005526 G1 to G0 transition Effects 0.000 claims description 2
- 238000004817 gas chromatography Methods 0.000 claims description 2
- 238000005070 sampling Methods 0.000 abstract description 10
- 230000035945 sensitivity Effects 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 238000004458 analytical method Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 51
- 239000000523 sample Substances 0.000 description 26
- 238000001514 detection method Methods 0.000 description 24
- 238000000926 separation method Methods 0.000 description 19
- 239000002904 solvent Substances 0.000 description 16
- 238000011084 recovery Methods 0.000 description 14
- 239000012088 reference solution Substances 0.000 description 13
- 239000011550 stock solution Substances 0.000 description 13
- 238000001228 spectrum Methods 0.000 description 11
- 239000012086 standard solution Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000007865 diluting Methods 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000007789 sealing Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000012488 sample solution Substances 0.000 description 6
- 239000012085 test solution Substances 0.000 description 5
- QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 description 4
- 229960003886 apixaban Drugs 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000013558 reference substance Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010812 external standard method Methods 0.000 description 2
- 238000003988 headspace gas chromatography Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000012421 spiking Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000012490 blank solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000017168 chlorine Nutrition 0.000 description 1
- 125000001309 chloro group Chemical class Cl* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000005264 electron capture Effects 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000011003 system suitability test Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Images
Landscapes
- Sampling And Sample Adjustment (AREA)
Abstract
The application provides a method for determining residual amount of trichloromethane in nitrophenylpyridone, and belongs to the technical field of drug analysis. The residual amount of trichloromethane in the nitrophenylpyridone is quantitatively detected by a headspace sampling method, so that the quality of the nitrophenylpyridone is effectively controlled. The method for measuring and controlling the residual amount of the trichloromethane in the nitrophenylpyridone has the advantages of simplicity, sensitivity, accuracy, reliability, good reproducibility and the like.
Description
Technical Field
The application relates to a method for determining residual amount of trichloromethane in nitrophenylpyridone, and belongs to the technical field of drug analysis.
Background
Nitrophenyl pyridone as key starting material of Apixaban (Apixaban) as anticoagulant drug and having molecular formula of C 15 H 17 N 3 O 4 The structural formula is as follows:
in the process of synthesizing the compound, organic solvents such as triethylamine, N-dimethylformamide, morpholine, ethanol, ethyl acetate, trichloromethane and the like are used, according to the boiling point and physical characteristics of the solvents, headspace sampling is adopted for a low-boiling-point solvent, and direct sampling is adopted for a high-boiling-point solvent for detection, so that the residual trichloromethane of the nitrophenylpyridone is controlled by headspace sampling, according to the supplement regulation of China pharmacopoeia 2020 edition and the ICH guiding principle, I stipulate that the residual trichloromethane of the nitrophenylpyridone is not more than 0.006%, and the response of the trichloromethane is small when the trichloromethane is detected under the condition of an FID detector and does not meet the detection requirement, so the compound is detected by an ECD detector.
The effective detection of the purity of the nitrophenylpyridone serving as an initial raw material of apixaban has important practical significance on the quality control in the subsequent synthesis process of apixaban, so that a method for simply and accurately determining the residual solvent in the nitrophenylpyridone is urgently needed to be developed.
Disclosure of Invention
In view of this, the application provides a method for determining the residual amount of trichloromethane in nitrophenylpyridone, which employs an ECD detector to perform headspace sampling to quantitatively detect the residual amount of trichloromethane in nitrophenylpyridone, thereby effectively controlling the quality of nitrophenylpyridone.
Specifically, the method is realized through the following scheme:
a method for determining the residual amount of trichloromethane in nitrophenylpyridone comprises the steps of adopting a headspace-gas chromatography method to carry out quantitative analysis on trichloromethane serving as a residual solvent in sample nitrophenylpyridone in a headspace sampling mode, wherein the chromatographic conditions are as follows: the DB-624 gas chromatographic column (30.0 m multiplied by 0.53mm multiplied by 3.0 mu m) using cyanopropylbenzene-dimethyl siloxane as a stationary phase is used, the initial column temperature is 45-55 ℃ and is kept for 10min, the temperature is increased to 200 ℃ at the speed of 20 ℃/min and is kept for 5min, the injection port temperature is 180-220 ℃, the detector is an ECD detector, the detector temperature is 300 ℃, the flow rate is 2.3-2.7 ml/min, the split ratio is 2:1, the nitrogen flow is 60ml/min, the headspace injection is balanced at 80 ℃ for 30min, the quantitative ring temperature is 90 ℃, and the transmission line temperature is 105 ℃.
The scheme adopts the headspace-gas chromatography and a headspace sampling method to realize quantitative detection of the residual amount of trichloromethane in the nitrophenylpyridone, thereby effectively controlling the quality of the nitrophenylpyridone, and having simple, sensitive, accurate and reliable operation and good reproducibility.
Further, as preferable:
the initial column temperature was 50 ℃ for 10min, and the temperature was raised to 200 ℃ at a rate of 20 ℃/min for 5min.
The injection port temperature is 200 ℃.
The flow rate is preferably 2.5ml/min.
The result of methodology verification shows that the method has stable chromatographic condition system, good linearity, high precision, high sensitivity of chromatographic conditions, good specificity and stability in 71h of the measured solution, and the durability test result shows that the micro changes of the flow rate, the column temperature and the temperature of the inlet do not influence the measurement of the trichloromethane in the nitrophenylpyridone.
The trichloromethane refers to an organic solvent used in a nitrophenylpyridone synthesis process, and referring to the appendix provisions of 2020 edition of Chinese pharmacopoeia and ICH guiding principles, I stipulate that residual trichloromethane in nitrophenylpyridone should not exceed 0.006%.
Drawings
FIG. 1 is a detection spectrum of a test sample and a standard solution in a solution suitable for the system of example 1;
FIG. 2 is a detection spectrum of a sample added with a standard solution at a flow rate of 2.3ml/min in example 2;
FIG. 3 is a detection spectrum of a sample added with a standard solution at a flow rate of 2.7ml/min in example 3;
FIG. 4 is a detection spectrum of a sample to be tested with a standard solution at a column temperature of 45 ℃ in example 4;
FIG. 5 is a detection spectrum of a sample to be tested with a standard solution at a column temperature of 45 ℃ in example 5;
FIG. 6 is a graph showing the detection of the sample-spiking solution at a sample inlet temperature of 180 ℃ in example 6;
FIG. 7 is a detection spectrum of a sample-spiking solution at an inlet temperature of 220 ℃ in example 7;
FIG. 8 shows chloroform (0.07295 mg/ml) detected using a headspace-FID detector.
Detailed Description
The present invention is further illustrated below with reference to specific examples, but is not limited to the scope of the implementation. In the following examples, the procedures and methods not described in detail are conventional methods known in the art, and reagents used are commercially available analytically or chromatographically pure without source or specification.
Example 1
The instruments and reagents used in this example were as follows:
the instrument comprises the following steps: gas chromatography, electron Capture Detector (ECD); electronic balance, mettler XSR 105; headspace sampler, agilent7697A.
Reagent: chloroform (chromatographically pure), ethanol (chromatographically pure), merck; ethyl acetate (analytical grade), group of national drugs; triethylamine (analytically pure), group of national drugs; dimethylsulfoxide (chromatographically pure), scharlau;
chromatographic conditions are as follows: chromatographic column DB-624 30.0 mm × 0.53mm × 3.0 μm; column temperature: keeping the temperature at 50 ℃ for 10min, and heating to 200 ℃ at the speed of 20 ℃/min and keeping the temperature for 5min; the temperature of a sample inlet is 200 ℃; the temperature of the detector is 300 ℃; the flow rate is 2.5ml/min; the split ratio is as follows: 20, 1; nitrogen flow rate: 60ml/min; headspace sampling, temperature balancing: 80 ℃ equilibration time: 30min; quantitative ring temperature: 90 ℃; transmission line temperature: 105 ℃; solvent: dimethyl sulfoxide (DMSO).
The test experiment procedure of this example is as follows:
control stock solutions: 30mg of trichloromethane is precisely weighed and placed in a 100ml volumetric flask, diluted to the scale with a solvent and shaken up to be used as a reference stock solution.
1) Control solution: precisely transferring 2.0ml to 200ml of reference stock solution into a volumetric flask, diluting the volumetric flask to a scale mark with a solvent, and shaking up to obtain a reference solution. Precisely transferring the solution into a headspace bottle of 5.0ml to 20ml, and sealing with a cover.
2) Positioning solution: accurately weighing 250mg of ethanol, ethyl acetate and triethylamine, placing the weighed materials into a 20ml volumetric flask, diluting the materials to a scale with a solvent, and shaking the materials uniformly to obtain a positioning solution stock solution. Precisely transferring 1.0ml of the positioning solution stock solution into volumetric flasks of different 50ml, diluting with a solvent to a scale, shaking up, precisely transferring 5.0ml to 20ml of the solution into a headspace flask, and covering and sealing to obtain the product.
3) Test solution: accurately weighing 5.0g of the product, placing the product in a 100ml volumetric flask, dissolving and diluting the product to a scale mark by using a solvent, and shaking the product uniformly to obtain a test solution. Precisely transferring the solution into a headspace bottle of 5.0ml to 20ml, and sealing by covering.
4) Adding a standard solution into a test sample: precisely weighing 5.0g of the product, placing the product in a 100ml volumetric flask, precisely transferring 1.0ml of reference substance stock solution into the same volumetric flask, dissolving and diluting the reference substance stock solution to a scale by using a solvent, and shaking the solution uniformly to be used as a sample and a standard solution. Precisely transferring the solution into a headspace bottle of 5.0ml to 20ml, and sealing with a cover.
5) Mixing the solution: precisely transferring 1.0ml of the positioning solution stock solution and 0.5ml of the reference substance stock solution into the same 50ml volumetric flask, diluting the solution to a scale with a solvent, and shaking up to obtain a mixed solution. Precisely transferring the solution into a headspace bottle of 5.0ml to 20ml, and sealing by covering.
1. Test of system suitability
Precisely transferring 5.0ml of solvent into a 20ml headspace bottle, capping, sealing, shaking, injecting into a gas chromatograph as a blank test, and recording the chromatogram. And taking a reference substance solution, a test sample adding standard solution, each impurity positioning solution, injecting into a gas chromatograph, recording a chromatogram, and calculating the residual solvent amount in the sample according to an external standard method. The results are shown in the following table 1 and figure 1, each component and trichloromethane can be effectively separated, and the separation degree and the theoretical plate number meet the requirements. The trichloromethane in the test solution is not detected and meets the regulation. Therefore, the method is suitable for detecting the target solvent.
Table 1: results of System suitability test
2. The detection limit and quantification limit experiments are as follows:
the detection limit concentration of chloroform is 0.0062 mug/ml by taking the signal-to-noise ratio 3:1 as the detection limit of the method, the signal-to-noise ratio 10 as the quantification limit of the method is 6.9, the quantification limit concentration is 0.0246 mug/ml, and the signal-to-noise ratio of the concentration is 19.8.
3. Linearity and range
In order to accurately measure the product and each impurity, linear investigation is carried out, namely, the relation between peak areas and concentrations of each substance in a certain range is designed, and each linear concentration starts to be tested from a quantitative limit concentration, and the method comprises the following steps: sampling and analyzing the chloroform linear solution, and drawing a linear regression equation of the chloroform.
The result shows that the standard curve equation of the concentration range of trichloromethane at 0.0246-6.1600 mug/ml (0.8% -205.3%) is y =1474.2446x +124.0855, R =1474.2446x + 2 ＝0.9967。
4. Accuracy and precision experiment
Preparing a recovery rate solution: precisely weighing 0.25g of a test sample stock solution into a 20ml volumetric flask, respectively precisely transferring a 50% reference solution, a 100% reference solution and a 200% reference solution into the 20ml volumetric flask, diluting the solutions to a scale by using a mobile phase, shaking the solutions uniformly, and preparing a 50%, 100% and 200% recovery rate solution.
Control stock solutions: 30mg of trichloromethane is precisely weighed and placed in a 100ml volumetric flask, diluted to the scale by a solvent and shaken up. Precisely transferring 10.0ml of the solution into a 100ml volumetric flask, diluting the solution to the scale with a solvent, and shaking the solution uniformly to serve as a reference stock solution.
Control solution: precisely transferring 10.0ml to 100ml of reference stock solution into a volumetric flask, diluting the volumetric flask to a scale mark with a solvent, and shaking up to obtain a reference solution.
Taking the sample, the reference solution and the recovery rate solution, respectively 5.0ml to 20ml of headspace bottles, capping and sealing, injecting samples, and recording chromatograms. The recovery rate of the trichloromethane is calculated according to an external standard method, the recovery rate is between 80 and 120 percent, the RSD value of the recovery rate is not more than 10.0 percent, and the method has high accuracy.
The method has the advantages that the accuracy is good because the RSD values of the peak areas of the unit concentrations of the solutions with the recovery rates of 50%, 100% and 200% of the impurities are all not more than 10.0% by taking the solution spectrums with the recovery rates of 50%, 100% and 200%.
5. Stability of
Taking blank solution, test solution, reference solution and test solution, standing at room temperature for 0, 3, 6, 9, 12, 25, 48 and 71 hr, sampling, analyzing, and recording chromatogram. The chloroform peak area RSD value of each solution is not more than 10% within 71 hours. Each solution was stable over 71 hours.
Example 2
This example is the same as the arrangement of example 1, except that: under the chromatographic conditions, the flow rate was 2.3ml/min. Taking the reference solution and the sample solution, injecting sample under the specified chromatographic condition, measuring, and recording chromatogram.
The chloroform detection result is shown in table 2, the obtained spectrum is shown in table 2, and the chromatographic condition separation effect is good as can be seen from table 2.
Table 2: chloroform test results
| Name of solution | Degree of separation | Number of theoretical plate | Peak area | Peak area recovery (%) |
| Control solution | Complete separation | 130136 | / | / |
| Sample adding solution | / | / | 4741.071 | 99.99 |
。
Example 3
This example is the same as the arrangement of example 1, except that: under the chromatographic conditions, the flow rate was 2.7ml/min. Taking the reference solution and the sample solution, adding the standard solution, performing sample injection measurement under the specified chromatographic condition, and recording the chromatogram.
The chloroform detection result is shown in table 3, the obtained chromatogram is shown in table 3, and the chromatographic condition separation effect is good as can be seen from table 3.
Table 3: chloroform test results
| Name of solution | Degree of separation | Number of theoretical plate | Peak area | Peak area recovery (%) |
| Control solution | Complete separation | 57035 | / | / |
| Sample labeling solution | / | / | 4937.002 | 102.57 |
。
Example 4
This example is the same as the arrangement of example 1, except that: in chromatographic conditions, the column temperature is 45 ℃. Taking the reference solution and the sample solution, injecting sample under the specified chromatographic condition, measuring, and recording chromatogram.
The chloroform detection result is shown in table 4, the obtained spectrum is shown in fig. 4, and the chromatographic condition separation effect is good as can be seen from table 4.
Table 4: chloroform assay results
| Name of solution | Degree of separation | Number of theoretical plate | Peak area | Peak area recovery (%) |
| Control solution | Complete separation of | 153974 | / | / |
| Sample adding solution | / | / | 4614.576 | 96.35 |
。
Example 5
This example is the same as the arrangement of example 1, except that: in chromatographic conditions, the column temperature is 55 ℃. Taking the reference solution and the sample solution, adding the standard solution, performing sample injection measurement under the specified chromatographic condition, and recording the chromatogram.
The chloroform detection result is shown in table 5, the obtained chromatogram is shown in table 5, and the chromatographic condition separation effect is good as can be seen from table 5.
Table 5: chloroform assay results
| Name of solution | Degree of separation | Number of theoretical plate | Peak area | Peak area recovery (%) |
| Control solution | Complete separation | 39898 | / | / |
| Sample labeling solution | / | / | 4917.722 | 99.35 |
。
Example 6
This example is the same as the arrangement of example 1, except that: in chromatographic conditions, the injection port temperature is 180 ℃. Taking the reference solution and the sample solution, adding the standard solution, performing sample injection measurement under the specified chromatographic condition, and recording the chromatogram.
The chloroform detection result is shown in table 6, the obtained spectrum is shown in fig. 6, and the chromatographic condition separation effect is good as can be seen from table 6.
Table 6: chloroform assay results
| Name of solution | Degree of separation | Number of theoretical plate | Peak area | Peak area recovery (%) |
| Control solution | Complete separation | 90894 | / | / |
| Sample adding solution | / | / | 4850.601 | 101.37 |
。
Example 7
This example is the same as the arrangement of example 1, except that: in chromatographic conditions, the injection port temperature is 220 ℃. Taking the reference solution and the sample solution, injecting sample under the specified chromatographic condition, measuring, and recording chromatogram.
The detection result of the trichloromethane is shown in the table 7, the obtained spectrum is shown in the table 7, and the chromatographic condition has good separation effect as can be seen from the table 7.
Table 7: chloroform assay results
| Name of solution | Degree of separation | Number of theoretical plate | Peak area | Peak area recovery (%) |
| Control solution | Complete separation of | 92394 | / | / |
| Sample labeling solution | / | / | 5024.368 | 99.22 |
。
As can be seen by comparing example 1 with examples 2-3, 4-5, 6-7: the method has good durability and slight difference in detection sensitivity.
The above scheme was applied to the preparation of nitrophenylpyridone, and chloroform in nitrophenylpyridone was detected, with the results shown in table 8.
Table 8: summary of application effects
The trichloromethane detection is direct detection, the sensitivity, specificity and the like far exceed the requirements of regulations, and a derivatization method is not adopted. Meanwhile, the trichloromethane contains 3 chlorines and one carbon atom, so that the response value of an FID (hydrogen flame ion detector) is low and cannot meet the requirement (figure 8), and the detection capability can be effectively improved by combining a headspace method with an ECD detector, so that the sensitivity is higher and the specificity is better.
Claims (5)
1. A method for measuring the residual amount of trichloromethane in nitrophenylpyridone is characterized by comprising the following steps: and (3) quantitatively analyzing the residual solvent trichloromethane in the sample nitrophenylpyridone in a headspace sample injection mode, wherein the chromatographic conditions are as follows: the method comprises the steps of using a DB-624 gas chromatographic column taking cyanopropylbenzene-dimethyl siloxane as a stationary phase, keeping the initial column temperature at 45-55 ℃ for 10min, raising the temperature to 200 ℃ at the rate of 20 ℃/min for 5min, keeping the temperature of a sample inlet at 180-220 ℃, using an ECD detector as a detector, keeping the temperature of the detector at 300 ℃, keeping the flow rate at 2.3-2.7 ml/min, keeping the split ratio at 2:1, keeping the nitrogen flow at 60ml/min, keeping the headspace sample injection at 80 ℃ for 30min, keeping the quantitative loop temperature at 90 ℃ and keeping the transmission line temperature at 105 ℃.
2. The method for determining the residual amount of chloroform in nitrophenylpyridone according to claim 1, characterized in that: the initial column temperature was 50 ℃ for 10min, and the temperature was raised to 200 ℃ at a rate of 20 ℃/min for 5min.
3. The method for determining the residual amount of chloroform in nitrophenylpyridone according to claim 1, characterized in that: the injection port temperature is 200 ℃.
4. The method for determining the residual amount of chloroform in nitrophenylpyridone according to claim 1, characterized in that: the flow rate is preferably 2.5ml/min.
5. The method for determining the residual amount of chloroform in nitrophenylpyridone according to claim 1, wherein the DB-624 gas chromatography column specification is: 30.0 m.times.0.53 mm.times.3.0. Mu.m.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310032373.6A CN115980226A (en) | 2023-01-10 | 2023-01-10 | Method for determining residual amount of trichloromethane in nitrophenylpyridone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310032373.6A CN115980226A (en) | 2023-01-10 | 2023-01-10 | Method for determining residual amount of trichloromethane in nitrophenylpyridone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115980226A true CN115980226A (en) | 2023-04-18 |
Family
ID=85970103
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310032373.6A Pending CN115980226A (en) | 2023-01-10 | 2023-01-10 | Method for determining residual amount of trichloromethane in nitrophenylpyridone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115980226A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114137095A (en) * | 2020-09-03 | 2022-03-04 | 北京渼颜空间生物医药有限公司 | Method for efficiently detecting residual solvent in poly-L-lactic acid and preparation thereof |
-
2023
- 2023-01-10 CN CN202310032373.6A patent/CN115980226A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114137095A (en) * | 2020-09-03 | 2022-03-04 | 北京渼颜空间生物医药有限公司 | Method for efficiently detecting residual solvent in poly-L-lactic acid and preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| 范桂强;宋更申;: "顶空气相色谱法测定氢溴酸加兰他敏中三氯甲烷残留量", 中国药业, no. 15, 5 August 2012 (2012-08-05), pages 2 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104655751B (en) | A kind of detect the method for organic solvent residual in dapoxetine | |
| CN113607843A (en) | Method for detecting residual solvent in sirolimus raw material medicine | |
| CN115166080B (en) | Method for detecting impurity A and impurity B in ifosfamide bulk drug | |
| CN111521698B (en) | Method for detecting residual solvent in setastine hydrochloride raw material medicine | |
| CN109580821B (en) | Method for detecting impurity succinic acid in S-benzylsuccinic acid | |
| CN109799298B (en) | Detection method of related substances in Perampanel bulk drug | |
| CN111929384A (en) | Method for determining content of residual methyl siloxane in organic silicon softening agent by using HS-GC external standard method | |
| CN111487340A (en) | Method for detecting organic residual solvent in obeticholic acid raw material medicine | |
| CN112710758A (en) | Method for detecting residual solvent in tapentadol hydrochloride raw material medicine | |
| CN114264752B (en) | Detection method of methyl bromoacetate | |
| CN115980226A (en) | Method for determining residual amount of trichloromethane in nitrophenylpyridone | |
| CN110361482A (en) | Linezolid monitor drug concentration kit and its detection method in a kind of blood | |
| CN110895264A (en) | Method for determining ethyl bromide in tenofovir alafenamide | |
| CN113030323A (en) | Method for detecting residual solvent in nilotinib bulk drug | |
| CN113092607A (en) | Detection method for residual solvent in loratinib raw material medicine | |
| CN111380992A (en) | Method for detecting residual quantity of organic solvent in formoterol bulk drug | |
| CN112710762A (en) | Method for measuring residual quantity of dimethyl sulfate | |
| CN111175388B (en) | Method for determining DCC content in indapamide bulk drug | |
| CN111595954B (en) | Method for detecting content of DCC and DCU in indapamide bulk drug | |
| CN110361486A (en) | Aripiprazole drug substance concentration monitor kit and its detection method in a kind of blood | |
| CN110849995B (en) | Detection method of DCU in indapamide bulk drug | |
| CN116930368B (en) | Detection method of settop alcohol isomer | |
| CN116500172B (en) | Detection method of amine solvent in acidic substrate | |
| CN112684039B (en) | Method for detecting residual quantity of organic solvent in imatinib raw material medicine | |
| CN114113395B (en) | Method for detecting ethyl p-toluenesulfonate in obeticholic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |