CN114544842A - Method for detecting N-bromosuccinimide in voriconazole - Google Patents
Method for detecting N-bromosuccinimide in voriconazole Download PDFInfo
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Abstract
The invention provides a method for detecting N-bromosuccinimide in voriconazole, wherein the N-bromosuccinimide is a material used in a voriconazole synthesis process, possibly remains in a voriconazole finished product, and the detection of the N-bromosuccinimide in the voriconazole is researched for controlling the content of the N-bromosuccinimide in the voriconazole finished product; the method is realized by using LC-MS detection, and in order to verify the effectiveness and feasibility of the method, the method is verified by referring to the ICH Q2 guiding principle. The method is simple to operate, consumes less time, can obtain accurate and effective data, has higher system applicability, and simultaneously meets standards in specificity, precision, accuracy, linearity, range and durability.
Description
Technical Field
The invention relates to the technical field of medical analysis, in particular to a method for detecting N-bromosuccinimide in voriconazole.
Background
Voriconazole is first marketed in the united states in 2002, is a product for further structural modification of fluconazole, belongs to the third-generation triazole antifungal drugs, has the characteristics of wide antibacterial spectrum, high bioavailability, safety, wide tissue distribution, capability of passing through blood brain barriers and the like, increases the clinical dosage year by year, has better antibacterial activity on candida, cryptococcus, aspergillus and the like, has better curative effect on clinically intractable aspergillus fumigatus infection, has the curative effect on aspergillus comparable to amphotericin B, is the first choice for treating pulmonary aspergillosis in south, and is also an empirical treatment drug for patients with neutrophilic granulocyte reduction and concomitant fever. Voriconazole is mainly metabolized by CYP2C19 enzyme in human body, and due to polymorphism of CYP2C19 gene, its action mechanism is that through competitive inhibition of fungal 14-alpha-sterol demethylase, biosynthesis of ergosterol (converted from lanosterol) which is an important component of cell membrane is hindered, and fluidity, permeability and activity of many enzymes on cell membrane are influenced, thus playing antifungal role.
The N-bromosuccinimide is a material used in the voriconazole synthesis process, possibly remains in a voriconazole finished product, and research personnel carry out method research on detection of the N-bromosuccinimide in the voriconazole in order to control the content of the N-bromosuccinimide in the voriconazole finished product; the invention provides a method for testing N-bromosuccinimide in voriconazole for the first time, which is realized by LC-MS detection, and meanwhile, in order to verify the effectiveness and feasibility of the method, the method is verified by referring to the ICH Q2 guiding principle.
Disclosure of Invention
The invention aims to provide a method for testing N-bromosuccinimide in voriconazole, which is simple, convenient, efficient and accurate, can shorten the testing time and achieve higher efficiency on the premise of not influencing the testing result, is verified by referring to the ICH Q2 guiding principle, and can be used for quality control of voriconazole bulk drugs.
In order to achieve the above purpose, the invention provides the following technical scheme:
a method for detecting N-bromosuccinimide in voriconazole comprises the following steps: (1) preparing solutions, namely respectively preparing a blank solution, a reference substance stock solution, a reference substance solution, a sensitivity solution and a test solution; the blank solution is diluent 1 and diluent 2; the reference substance stock solution and the reference substance solution comprise N-bromosuccinimide, a diluent 1 and a diluent 2; the sensitivity solution comprises N-bromosuccinimide, a diluent 1 and a diluent 2; the test solution comprises voriconazole, a diluent 1 and a diluent 2;
(2) the determination method comprises the following steps: respectively injecting the blank solution, the sensitivity solution, the reference solution and the test solution into a liquid chromatograph, and recording a chromatogram, wherein the chromatogram conditions are as follows: a chromatographic column: octadecylsilane chemically bonded silica is used as a filler; sample introduction amount: 20 mu l of the mixture; column temperature: 30 ℃; flow rate: 0.4 ml/min; the eluent is a mobile phase A-mobile phase B system; mobile phase a was 10mM ammonium acetate solution (containing 0.1% glacial acetic acid); the mobile phase B is as follows: acetonitrile;
the gradient of mobile phase a and mobile phase B is as follows:
the ion source parameters were as follows:
further, the preparation steps of the blank solution are as follows: blank solutions are diluent 1 and diluent 2, wherein the diluent 1 is acetonitrile: acetone =1:1 (V/V, volume ratio), the diluent 2 is water;
the preparation steps of the reference stock solution are as follows: taking an N-bromosuccinimide reference substance, precisely weighing, placing in a volumetric flask, adding the diluent 1 to dissolve and dilute to a scale, and shaking up; precisely measuring the solution, placing the solution in a volumetric flask, adding the diluent 2 to dilute the solution to a scale, and shaking up to obtain a reference substance stock solution;
the preparation steps of the reference substance solution are as follows: precisely measuring a reference substance stock solution, placing the reference substance stock solution in a volumetric flask, adding the diluent 1 to dilute to a scale, and shaking up; precisely measuring the solution, placing in a volumetric flask, adding the diluent 2 to dilute to a scale, and shaking up to obtain a reference solution;
the preparation steps of the sensitivity solution are as follows: precisely measuring a reference substance solution, placing the reference substance solution in a volumetric flask, adding a blank solution to dilute the reference substance solution to a scale, and shaking up to obtain a sensitivity solution;
the preparation steps of the test solution are as follows: taking a test sample, precisely weighing, placing in a volumetric flask, adding the diluent 1, ultrasonically dissolving, diluting to a scale, and shaking uniformly; precisely measuring the solution, placing in a volumetric flask, adding the diluent 2 to dilute to a scale, shaking up to separate out a sample, and filtering with a filter membrane to obtain a test solution;
the glacial acetic acid and the ammonium acetate are AR and above;
the acetonitrile, the ultrapure water and the acetone are HPLC;
the N-bromosuccinimide reference substance is purchased from other places;
the chromatographic column may be Thermo AcclaimTM120C 18120A 4.6X 150mm, 5 μm, or a column of comparable performance.
The method for measuring the content of the N-bromosuccinimide further comprises method verification before detection, wherein the method verification is that according to the chromatographic conditions of formal detection, the measurement result is as follows:
advantageous effects
According to the technical scheme, the detection method disclosed by the invention has high chromatographic peak separation degree on the N-bromosuccinimide in the voriconazole, has high system applicability, and meets the standards in specificity, precision, quantification limit, detection limit, accuracy, linearity, range and durability. In order to confirm the residual quantity of the N-bromosuccinimide in the voriconazole, the method utilizes a convenient and quick liquid chromatography-mass spectrometry combined method, and verifies the method for proving the effectiveness and feasibility of the method. The detection of the N-bromosuccinimide in the voriconazole can be used for monitoring the quality of the voriconazole bulk drug and the preparation. The invention firstly provides the detection of the N-bromosuccinimide in the voriconazole by using a gas chromatography-mass spectrometry combined method, and has the characteristics of high accuracy, high precision, good reproducibility, good stability, strong specificity and the like.
Drawings
FIG. 1 is a liquid chromatogram of an empty solution in examples 2, 3, 4, and 5;
FIG. 2 is a liquid chromatogram of the sensitive solutions of examples 2 and 5;
FIG. 3 is a liquid chromatogram of a control solution in examples 2, 3 and 4;
FIG. 4 is a liquid chromatogram of the test solution of example 3;
FIG. 5 is a liquid chromatogram of the selective solution of example 3;
FIG. 6 is a liquid chromatogram of the test solution (labeled) in example 4;
FIG. 7 is a liquid chromatogram of the LOQ solution of example 5;
FIG. 8 is a liquid chromatogram of the LOD solution of example 5;
FIG. 9 shows the linear relationship of N-bromosuccinimide.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
Example 1
(1) Experimental materials and instrumentation conditions
Experimental materials: acetonitrile, manufacturer: merck; glacial acetic acid, manufacturer: guangdong Guanghua science and technology Co., Ltd; ammonium acetate, manufacturer: sigma-aldrich; acetone, manufacturer: west longa science, inc; n-bromosuccinimide, manufacturer: shanghai Michelin Biochemical technology, Inc.; voriconazole, manufacturer: zhuhairun pharmaceutical products, Inc.; water, manufacturer: watson.
The instrument comprises the following steps: liquid chromatography mass spectrometer: agilent Infinity 1290 UHPLC + Agilent 6470 QQQ-MS; electronic analytical balance XSE205DU, ME 204E; a chromatographic column: acclaimTM 120 C18 120A 4.6×150mm，5µm。
Respectively injecting the blank solution, the sensitivity solution, the reference solution and the test solution into a liquid chromatograph, and recording a chromatogram, wherein the chromatogram conditions are as follows: a chromatographic column: octadecylsilane chemically bonded silica is used as a filler; sample introduction amount: 20 mu l of the mixture; column temperature: 30 ℃; flow rate: 0.4 ml/min; the eluent is a mobile phase A-mobile phase B system; mobile phase a was 10mM ammonium acetate solution (containing 0.1% glacial acetic acid); the mobile phase B is as follows: acetonitrile;
the gradient of mobile phase a and mobile phase B is as follows:
the ion source parameters were as follows:
(2) experimental procedure
Preparation of blank solution: taking a 20ml volumetric flask, adding 8ml of diluent 1, adding diluent 2 to dilute until scales are scaled and shaking up to obtain a blank solution;
preparing a reference substance stock solution: taking about 21mg of N-bromosuccinimide reference substance, precisely weighing, placing in a 20ml volumetric flask, adding the diluent 1 to dissolve and dilute to a scale, and shaking up; precisely measuring 250 μ l of the above solution, placing in a 100ml volumetric flask, adding diluent 1 to dilute to scale, and shaking to obtain reference stock solution (concentration: 2.625 μ g/ml);
preparing a reference solution (N-bromosuccinimide positioning solution): precisely measuring 1.0ml of reference stock solution, placing the reference stock solution in a 5ml volumetric flask, adding the diluent 1 to dilute the reference stock solution to a scale, and shaking up; precisely measuring 4.0ml of the solution, placing the solution in a 10ml volumetric flask, adding the diluent 2 to dilute to a scale, and shaking up to obtain a reference solution (the concentration: 210 ng/ml);
preparing a sensitivity solution: precisely measuring 5.0ml of reference solution, placing in a 10ml volumetric flask, adding the blank solution to dilute to scale, and shaking up to obtain a sensitive solution (the concentration: 105 ng/ml);
preparing a test solution (voriconazole positioning solution): taking about 1.4g of a sample, precisely weighing, placing in a 5ml volumetric flask, adding the diluent 1, ultrasonically dissolving, diluting to a scale, and shaking up; precisely measuring 4.0ml of the solution, placing in a 10ml volumetric flask, adding the diluent 2 to dilute to a scale, shaking uniformly to precipitate a sample, and filtering with a 0.22 μm filter membrane to obtain a test solution (concentration: 112 mg/ml);
preparation of the selective solution: precisely weighing about 1.4g of a sample, placing the sample in a 5ml volumetric flask, precisely weighing 1.0ml of a reference substance stock solution, placing the sample in the volumetric flask, adding a diluent 1, ultrasonically dissolving and diluting to a scale, and shaking up; precisely measuring 4.0ml of the solution, putting the solution into a 10ml volumetric flask, adding the diluent 2 to dilute the solution to a scale, shaking the solution evenly to separate out a sample, and filtering the sample by using a 0.22 mu m filter membrane to obtain a selective solution (the concentration is 112mg/ml of voriconazole and 210ng/ml of N-bromosuccinimide);
preparing a test solution (adding a label): precisely weighing about 1.4g of a test sample, placing the test sample in a 5ml volumetric flask, precisely weighing 1.0ml of a reference substance stock solution, placing the reference substance stock solution in the volumetric flask, adding the diluent 1, ultrasonically dissolving and diluting to a scale, and shaking up; precisely measuring 4.0ml of the solution, putting the solution into a 10ml volumetric flask, adding the diluent 2 to dilute the solution to a scale, shaking the solution uniformly to separate out a sample, and filtering the sample by using a 0.22 mu m filter membrane to obtain a sample solution (added with a standard) (the concentration is 112mg/ml of voriconazole and 210ng/ml of N-bromosuccinimide);
preparing the LOQ solution: and adjusting the dilution ratio to ensure that the S/N value of the N-bromosuccinimide is not less than 10 according to the S/N value of the N-bromosuccinimide obtained from the sensitivity solution. 6 portions of the mixture are prepared by the same method.
Ninthly, preparation of LOD solution: precisely measuring 3.0ml of LOQ solution, placing the LOQ solution in a 10ml volumetric flask, adding the blank solution to dilute the LOQ solution to a scale, and shaking up to obtain the LOD solution.
After the system is stabilized, 1 needle of blank solution, 1 needle of sensitivity solution and 6 needles of reference solution are added, and chromatogram is recorded.
Example 2 detection method of the invention System suitability test
The system applicability is realized by measuring the S/N value of the N-bromosuccinimide in the sensitivity solution and the RSD of the peak area of the N-bromosuccinimide in the 6-needle reference substance solution. The S/N value of the N-bromosuccinimide in the sensitivity solution is required to be more than or equal to 10; the RSD of the peak area of the N-bromosuccinimide in the 6-needle reference solution is not more than 10.0 percent. In order to confirm the system applicability in the sequence operation process, 1 needle of reference substance solution is fed every about 8 hours and at the end of the sequence in the verification process, and the RSD of the peak area of the N-bromosuccinimide in the continuous 6 needles of reference substance solution is required to be not more than 10.0 percent; if the range is exceeded, an evaluation survey should be conducted.
Preparing blank solution, sensitivity solution and reference solution as described in example 1, and performing chromatogram by using blank solution 1 needle, sensitivity solution 1 needle and reference solution 6 needle under the chromatographic conditions described in example 1, wherein the chromatogram is shown in FIG. 1, FIG. 2 and FIG. 3, and the conversion results according to the formula are shown in the following table:
example 3 specificity test of the detection method of the invention
The specificity of the method is that the detection is not interfered by measuring a blank solution; the resolution between the N-bromosuccinimide and the adjacent peak in the selective solution is realized, the blank solution is required to have no interference to the detection, and the resolution between the N-bromosuccinimide and the adjacent peak in the selective solution is required to be not less than 1.5.
Preparing a blank solution, a reference solution, a test solution and a selective solution as described in example 1, and feeding the blank solution 1 needle, the reference solution 1 needle, the test solution 1 needle and the selective solution 1 needle under the chromatographic conditions described in example 1 to obtain chromatograms, which are shown in fig. 1, fig. 3, fig. 4 and fig. 5, and the conversion results according to the formulas are shown in the following tables:
example 4 precision testing of the assay methods of the invention
The repeatability is realized by testing the RSD of the measurement result of 6 parts of test solution (added standard), and the RSD of the measurement result of N-bromosuccinimide in 6 parts of test solution (added standard) is required to be not more than 10.0%.
Preparing blank solution, reference solution and sample solution (adding label) as described in example 1, after the system is balanced, adding 1 needle of blank solution, 6 needles of reference solution, 1 needle of blank solution and 6 samples solution (adding label) respectively, recording chromatogram, and obtaining specificity detection results as follows according to fig. 1, fig. 3 and fig. 6:
example 5 quantitation and detection limits of the detection methods of the invention
The quantitative limit and the detection limit are realized by detecting the ratio of the response signal to the noise, and the signal-to-noise ratio (S/N) of the quantitative limit should not be less than 10: 1, the signal-to-noise ratio (S/N) of the detection limit should not be less than 3: 1; under the quantitative limit concentration level, 6 parts of quantitative limit solution are repeatedly inspected, and the RSD of the unit concentration peak area of the N-bromosuccinimide in 6 parts of LOQ solution is required to be not more than 20.0 percent; LOQN-bromosuccinimide should not be greater than 0.9ppm, and S/N is not less than 10; the S/N of the N-bromosuccinimide in the LOD solution is more than or equal to 3, and the LOD is less than LOQ.
Blank, sensitivity, LOQ and LOD solutions were prepared as described in example 1. After the system is balanced, 1 pin of blank solution, 1 pin of sensitivity solution, 1 pin of 6 parts of LOQ solution and 1 pin of LOD solution are added, and chromatograms are recorded, such as figure 1, figure 2, figure 7 and figure 8. The results obtained are shown in the following table:
example 6 accuracy of the detection method of the invention
Accuracy is achieved by recovery between measured concentration and theoretical concentration of the measured component and total RSD of recovery (N = 9), requiring addition of an accuracy solution of LOQ concentration, 100% limit concentration, 150% limit concentration, N-bromosuccinimide recovery should be between 70.0% and 130.0%, and total RSD of recovery (N = 9) should be no more than 20.0%.
Example 7 solution stability of the assay method of the invention
And (3) observing the rule that the reference substance solution, the test solution and the selective solution are placed at room temperature for a period of time and then are injected, and detecting the change of the detection result along with the time, so as to provide reference for the placing time of the reference substance solution and the test solution during detection.
The method comprises the following steps: compared with the reference solution of 0hr, the recovery rate of N-bromosuccinimide is between 80.0% and 120.0% during the reference solution is inspected at room temperature, and no obvious change trend exists, so that the reference solution is stable during the inspection at room temperature;
if the test solution detects N-bromosuccinimide within 0hr, the test solution is placed at room temperature for a period of time, the variation value of the measurement result is within 20% of the limit of the N-bromosuccinimide, and no obvious variation trend exists, so that the test solution is stable during the investigation at room temperature; if the test solution is not detected after 0hr, and if the test solution is still not detected after being placed at room temperature for a period of time, the test solution is stable during the examination period at room temperature;
the selective solution is placed at room temperature for a period of time, the recovery rate of the N-bromosuccinimide is between 80.0% and 120.0%, and no obvious change trend exists, so that the selective solution is stable during the room temperature investigation.
Claims (2)
1. A method for detecting N-bromosuccinimide in voriconazole is characterized by comprising the following steps: (1) preparing solutions, namely respectively preparing a blank solution, a reference substance stock solution, a reference substance solution, a sensitivity solution and a test solution; the blank solution is diluent 1 and diluent 2; the reference substance stock solution and the reference substance solution comprise N-bromosuccinimide, a diluent 1 and a diluent 2; the sensitivity solution comprises N-bromosuccinimide, a diluent 1 and a diluent 2; the test solution comprises voriconazole, a diluent 1 and a diluent 2;
(2) the determination method comprises the following steps: respectively injecting the blank solution, the sensitivity solution, the reference solution and the test solution into a liquid chromatograph, and recording a chromatogram, wherein the chromatogram conditions are as follows: and (3) chromatographic column: octadecylsilane chemically bonded silica is used as a filler; sample injection amount: 20 mu l of the mixture; column temperature: 30 ℃; flow rate: 0.4 ml/min; the eluent is a mobile phase A-mobile phase B system; mobile phase a was 10mM ammonium acetate solution (containing 0.1% glacial acetic acid); the mobile phase B is as follows: acetonitrile;
the gradient of mobile phase a and mobile phase B is as follows:
the ion source parameters were as follows:
2. the method for detecting N-bromosuccinimide in voriconazole according to claim 1, wherein the blank solution is prepared by the steps of: blank solutions are diluent 1 and diluent 2, wherein the diluent 1 is acetonitrile: acetone =1:1 (V/V, volume ratio), the diluent 2 is water;
the preparation steps of the reference stock solution are as follows: taking an N-bromosuccinimide reference substance, precisely weighing, placing in a volumetric flask, adding the diluent 1 to dissolve and dilute to a scale, and shaking up; precisely measuring the solution, placing the solution in a volumetric flask, adding the diluent 2 to dilute the solution to a scale, and shaking up to obtain a reference substance stock solution;
the preparation steps of the reference substance solution are as follows: precisely measuring a reference substance stock solution, placing the reference substance stock solution in a volumetric flask, adding the diluent 1 to dilute the reference substance stock solution to a scale, and shaking up; precisely measuring the solution, placing in a volumetric flask, adding the diluent 2 to dilute to a scale, and shaking up to obtain a reference solution;
the preparation steps of the sensitivity solution are as follows: precisely measuring a reference substance solution, placing the reference substance solution in a volumetric flask, adding a blank solution to dilute the reference substance solution to a scale, and shaking up to obtain a sensitivity solution;
the preparation steps of the test solution are as follows: taking a test sample, precisely weighing, placing in a volumetric flask, adding the diluent 1, ultrasonically dissolving, diluting to a scale, and shaking uniformly; precisely measuring the solution, placing in a volumetric flask, adding the diluent 2 to dilute to a scale, shaking up to separate out a sample, and filtering with a filter membrane to obtain a test solution;
the glacial acetic acid and the ammonium acetate are AR and above;
the acetonitrile, the ultrapure water and the acetone are HPLC;
the N-bromosuccinimide reference substance is purchased from other places;
the chromatographic column may be Thermo AcclaimTM120C 18120A 4.6X 150mm, 5 μm, or a column of comparable performance.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117471001A (en) * | 2023-12-26 | 2024-01-30 | 山东百诺医药股份有限公司 | Method for measuring content of N-bromosuccinimide in starting material of Rate Lu Geli |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009024214A1 (en) * | 2007-08-21 | 2009-02-26 | Axellia Pharmaceuticals Aps | Process for the production of voriconazole |
| CN107643351A (en) * | 2017-11-01 | 2018-01-30 | 浙江科瑞医药科技有限公司 | A kind of method of bromo-succinimide and succimide content in detection sodium ozagrel bulk drug |
| CN108982694A (en) * | 2018-07-27 | 2018-12-11 | 西藏多瑞医药有限公司 | A kind of detection method of the N- bromo-succinimide in relation to substance |
| CN109212048A (en) * | 2017-07-07 | 2019-01-15 | 常州齐晖药业有限公司 | The detection method of impurity content in a kind of voriconazole |
| CN111704606A (en) * | 2020-06-11 | 2020-09-25 | 广东隆赋药业股份有限公司 | Preparation method of voriconazole intermediate |
-
2020
- 2020-11-26 CN CN202011327084.1A patent/CN114544842B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009024214A1 (en) * | 2007-08-21 | 2009-02-26 | Axellia Pharmaceuticals Aps | Process for the production of voriconazole |
| CN109212048A (en) * | 2017-07-07 | 2019-01-15 | 常州齐晖药业有限公司 | The detection method of impurity content in a kind of voriconazole |
| CN107643351A (en) * | 2017-11-01 | 2018-01-30 | 浙江科瑞医药科技有限公司 | A kind of method of bromo-succinimide and succimide content in detection sodium ozagrel bulk drug |
| CN108982694A (en) * | 2018-07-27 | 2018-12-11 | 西藏多瑞医药有限公司 | A kind of detection method of the N- bromo-succinimide in relation to substance |
| CN111704606A (en) * | 2020-06-11 | 2020-09-25 | 广东隆赋药业股份有限公司 | Preparation method of voriconazole intermediate |
Non-Patent Citations (3)
| Title |
|---|
| MIKE BUTTERS 等: "Process Development of Voriconazole: A Novel Broad-Spectrum Triazole Antifungal Agent" * |
| 佟丽华 等: "抗真菌新药伏立康唑的合成工艺优化" * |
| 王思袭 等: "伏立康唑合成路线图解" * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117471001A (en) * | 2023-12-26 | 2024-01-30 | 山东百诺医药股份有限公司 | Method for measuring content of N-bromosuccinimide in starting material of Rate Lu Geli |
| CN117471001B (en) * | 2023-12-26 | 2024-03-26 | 山东百诺医药股份有限公司 | Method for measuring content of N-bromosuccinimide in starting material of Rate Lu Geli |
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